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Chronic Disease, Global Health, Medical Apps, Public Health, Public Safety, Research

The right tool for the job: Creating a waterborne disease reporting system for Nepal

Fig 3When I last spoke with cholera expert Eric Jorge Nelson, MD, PhD, he was about to field test a tool to help doctors in Bangladesh diagnose, treat and report cholera outbreaks in real time using a smartphone app. Now that this reporting system is up and running, he’s working to create similar reporting systems for doctors elsewhere. But, as he learned in the remote regions of Nepal, a high-tech approach isn’t always the best approach.

Nelson was invited to Nepal by his colleague Jason Andrews, MD, an infectious disease expert who works with the Dhulikhel Hospital, to share his expertise on recognizing, responding to and containing cholera outbreaks.

Like Bangladesh, Nepal has seasonal outbreaks of waterborne diseases, including cholera, Typhoid, viral hepatitis and dysentery, that ebb and flow with the monsoon seasons. What made the situation in Nepal urgent, Nelson told me, is that waterborne diseases can also arise after natural disasters, and a 7.8 magnitude earthquake struck Nepal last spring and more than 100 aftershocks have hit the region since.

An added complication, Andrews explained, was that Nepal’s government wasn’t scaling up waterborne disease surveillance in the rural areas following the earthquakes. “Our colleagues at Dhulikhel Hospital, by contrast, were extremely proactive and committed to setting up a system before an outbreak hit,” Andrews said.

Nelson was only in Nepal for about 48 hours, but during those two days he and Andrews began to tackle the problem of how to prevent a large-scale cholera outbreak there. At first, it seemed plausible that the smartphone app designed for Bangladesh would work in Nepal — but Nelson said they quickly realized that Nepal’s post-earthquake infrastructure wasn’t suited to a smartphone reporting system.

“There were few resources in Nepal and little time to ramp-up a reporting system,” Nelson said. “Charging a smartphone requires a stable power supply, and although the 3G networks within the city were fine, they weren’t good in the canyons.”

This is where Andrews’ expertise came in. His knowledge of Nepal and experience building surveillance systems with “just the bare bones” (as he put it) helped the team reverse engineer the smartphone app Nelson used in Bangladesh and use elements of it to create a paper-based surveillance system that’s better suited to the post-earthquake situation in rural Nepal.

“This was a risky endeavor,” Andrews said. “We didn’t have funding so we drew upon our own existing resources. Funding takes a while, the earthquake was in April and the monsoon hits in June. If we had waited, the monsoon season would have passed. We realized we could scale this up really quickly with minimal resources and it was worth the risk.”

Now, the team’s paper-based system has been working for several months and Nepal’s government is interested in replicating the model at a larger level.

“I learned two important lessons during my trip to Nepal,” Nelson told me. “I learned the power of winnowing a complicated process, like our smartphone app, down. I also learned how we can broaden what we did in Bangladesh for a wider community.”

He continued: “Hopefully we are emerging from the idea that mobile technology is a panacea. We need to be open to considering high — or low — tech strategies depending on what the on-the-ground situation is. We happened to have two very different design challenges in Bangladesh and Nepal: Mobile was best for Bangladesh and paper was best for Nepal. You have to build what the end-user desires, is feasible and is viable. I think the mhealth field is waking up to this reality.”

Previously: A tale of two earthquakes: Stanford doctor discusses responses to the Nepal and Haiti disastersReporting and treating cholera: Soon, there could be an app for thatDay 1: Arriving in Nepal to aid earthquake victims and Using social media to fight cholera
Photo courtesy of U.u.H. Schmel and R.K. Mahato

Biomed Bites, Microbiology, Research, Videos

Unwelcome guests: How viruses take over cells

Unwelcome guests: How viruses take over cells

Welcome to Biomed Bites, a weekly feature that introduces readers to some of Stanford’s most innovative biomedical researchers.

Viruses are the ultimate uninvited guests. They barge in and make themselves perfectly at home — feeling free to use, say, your waffle maker to whip up a nice breakfast and to co-opt your favorite easy chair for their own purposes.

In cells, many mysteries remain about how viruses take over enzymes and other systems in cells to reproduce.

That’s exactly what Peter Sarnow, PhD, professor and chair of microbiology and immunology, and his team investigate. From the video above:

My lab is interested in studying virus-host interactions. In particular, we’re interested in learning how viruses subvert functions from the host cell such as using the ribosomes to synthesize their own proteins.

He explains a recent discovery his team has worked on that may lead to better treatments for hepatitis C infections. “I’m very optimistic this will be beneficial and is a good example of how basic science really translates into translational medicine,” Sarnow says.

Learn more about Stanford Medicine’s Biomedical Innovation Initiative and about other faculty leaders who are driving biomedical innovation here.

Previously: Why are viruses so wily? One research thinks she knows — and is working to thwart them, Ending enablers: Stanford researcher examines genes to find virus helpers and To screen or not to screen for hepatitis C

Big data, Cancer, Genetics, Precision health, Research, Stanford News, Stem Cells

Stem-cell knowledge may help outcomes for colon-cancer patients, says Stanford study

Stem-cell knowledge may help outcomes for colon-cancer patients, says Stanford study

Pinpointing which colon cancer patients need chemotherapy in addition to surgery can be difficult. Studies have suggested that those with stage-2 disease aren’t likely to benefit from chemotherapy, so doctors may chose to bypass the treatment and its toxic side effects.

Now cancer biologist Michael Clarke, MD, working with former postdoctoral scholars Piero Dalerba, MD, and Debashis Sahoo, PhD, have found a way to identify a small but significant minority of stage-2 patients who differ from their peers: They have a poorer overall prognosis, but they are also more likely than other stage-2 patients to benefit from additional chemotherapy. The research was published today in the New England Journal of Medicine.

This research is one of the first examples of how we can use our growing knowledge of stem cell biology to improve patient outcomes

From our press release:

Clarke and his colleagues have been studying the connection between stem cells and cancer for several years. For this study, Dalerba and Sahoo sought to devise a way to identify colon cancers that were more stem-cell-like, and thus likely to be more aggressive. They looked for a gene that was expressed in more mature cells but not in stem or progenitor cells. They did this by using a novel bioinformatics approach that drew on their knowledge of stem cell biology to identify developmentally regulated genes important in colon tissue maturation.

Because they knew from previous research by Dalerba in the Clarke laboratory that stem and immature colon cells express a protein called ALCAM, Dalerba and Sahoo looked for genes whose protein product was negatively correlated with ALCAM expression. “We reasoned that those proteins would likely be involved in the maturation of colon tissue and might not be found in more aggressive, immature cancers,” Sahoo said.

Finally, to ensure their results would be useful to doctors, the researchers added another criterion: The gene had to make a protein that was easily detectable by an existing, clinical-grade test.

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Addiction, Cancer, Genetics, Public Health, Research, Stanford News

For some African Americans, light smokers may not have lower lung cancer risk than heavy ones

For some African Americans, light smokers may not have lower lung cancer risk than heavy ones

CigaretteAlthough the relationship between smoking and lung cancer has been established beyond any doubt, it’s still difficult to know how a patient’s ethnicity might play into risk assessment. But it’s clear that it has a role. Lung cancer is the leading cause of cancer death in this country, and it disproportionately affects African Americans. Doctors are struggling to understand the interactions between genes and environment that contribute to lung cancer risk in all populations.

Physician scientist Sean David, MD, DPhil, and a multidisciplinary team of colleagues recently published in EBioMedicine the results of a study suggesting that African Americans who carry a panel of risky genetic sequences may be at higher risk for the disease, even if they are light smokers.

The study involved analyses of more than 7,000 Women’s Health Initiative participants and nearly 2,000 participants in a lung cancer case-control study with collaborators from multiple institutions in the United States.

As David explained to me in an email:

All smokers are at heightened risk for lung cancer, particularly those possessing high-risk genotypes. Our study suggests that African American light smokers are not at lower risk than heavy smokers if they possess certain genotypes, but that smoking more cigarettes does markedly increase lung cancer risk in individuals without these high-risk genotypes. These conclusions reinforce the message that light or heavy smoking is a risky proposition for African Americans, who can benefit from smoking cessation and evidence-based lung cancer screening services.

The researchers identified six nucleotide changes that appeared to affect the relationship between cigarettes smoked per day and lung cancer risk in African American smokers – all on chromosome 15. Although the nucleotide changes, called single nucleotide polymorphisms, or SNPs, had been associated with lung cancer risk in previous studies, this is the first time the risk has been tied to daily cigarette exposure in African Americans.

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Big data, Cardiovascular Medicine, Health and Fitness, Obesity, Research

High BMI and low fitness linked with higher hypertension risk

High BMI and low fitness linked with higher hypertension risk

USMC-120412-M-UY543-003Unfit adolescents who have a high body mass index are more likely to suffer from hypertension when they are older than their peers, according to a new study from researchers at Stanford and Lund University in Sweden.

The paper, the first to discover this connection, was published today in JAMA Internal Medicine.

Lead author Casey Crump, MD, PhD, who recently left Stanford to join the Mount Sinai School of Medicine in New York, and his colleagues tapped a unique data source to uncover the relationship: the Swedish military. In the past in Sweden, all males had to join the military at age 18, and Crump and his team examined fitness and health records from more than 1.5 million military conscripts between 1969 and 1997. Thanks to the Swedish national health-care system, they were also able to obtain follow-up information to see when and if adults were diagnosed with hypertension.

I exchanged emails about the study with Crump, who is vice chair for research in the Department of Family Medicine and Community Health; below is our conversation.

Why did you decide to look at this?

Low physical fitness and obesity are very common, modifiable, and have an enormous public health impact.

What is the primary lesson from this work?

We found that both overweight/obesity and low aerobic fitness at age 18 were linked with higher long-term risk of hypertension in adulthood. Importantly, low aerobic fitness was a strong risk factor for hypertension even among those with normal body mass index (BMI). These findings suggest that interventions to prevent hypertension should begin early in life and include not only weight control but also aerobic fitness, even among persons with normal BMI.

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Autoimmune Disease, Immunology, Neuroscience, Research, Stanford News

New perspective: Potential multiple sclerosis drug is actually old (and safe and cheap)

New perspective: Potential multiple sclerosis drug is actually old (and safe and cheap)

new perspectiveAbout 400,000 people in the United States are affected by multiple sclerosis (often referred to by the acronym MS), an autoimmune disorder in which rogue immune cells attack the insulating layer surrounding many nerve cells in the central nervous system.  Some 200 new cases are diagnosed every week in the U.S.

I wrote a while back about a study by Paul Bollyky, MD, PhD, showing that blocking production of a naturally made substance in the body could potentially protect against type 1 diabetes, another autoimmune disorder in which the body’s immune system attacks the pancreas’s insulin-producing cells (the only place where insulin is made). It now appears possible that the same drug Bollyky’s team used to achieve that benefit may also be beneficial in MS.

The substance in question — hyaluronan, a hefty, complex carbohydrate substance — is usually present at trace concentrations in the extracellular matrix that pervades all tissues and, among other things, helps glue those tissues’ constituent cells together. Intriguingly, hyaluronan levels spike markedly at the site of an injury. If you twist your ankle or stub your toe, the swelling you see afterwards is mainly due to hyaluronan, which is prone to soaking up water. That causes fluid buildup, aka swelling,  in the injured region — a cardinal feature of inflammation, along with heat, redness and pain.

In a new study published in Proceedings of the National Academy of Sciences, Bollyky and his colleagues show that hyaluronan also abounds in sites of autoimmune attack in MS patients’ brains after they induced a mousie version of MS in laboratory mice. They confirmed that hyaluronan likewise accumulates near the mice’s MS lesions. And they showed that blocking new hyaluronan synthesis in the mice before symptoms developed prevented many of the mice from succumbing to MS and delayed disease onset and severity in those who did get it, while — importantly — blocking hyaluronan synthesis after symptoms developed alleviated those symptoms.

Perhaps most interesting of all: The drug they used to do that is already on the market for other indications.

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Big data, Genetics, Precision health, Research

Precision health in action — The hunt for families with a high-cholesterol disorder

Precision health in action — The hunt for families with a high-cholesterol disorder

3440634940_efbb70438d_zIf I don’t know I have a genetic disease, I’m not very likely to seek treatment or change my lifestyle. This lack of knowledge, obviously, leaves me medically vulnerable.

To find people who have one such disease — familial hypercholesterolemia (FH), a condition that causes high levels of LDL cholesterol — biomedical data specialist Nigam Shah, MBBS, PhD, and cardiologist Joshua Knowles, MD, PhD, are applying the powers of big data. Their work has been called a prime example of precision health.

A recent feature by FiveThirtyEight explains their work:

They started by identifying about 120 people known to have FH (true positives) from Stanford’s network of hospitals and doctors’ offices, and some people with high LDL who don’t have the genetic disorder (true negatives). Shah then began to train a computer to spot people with FH by letting it look through those patients’ files and to identify patterns in things like cholesterol levels, age, and the medicine patients were prescribed. The researchers then deployed this algorithm to look for undiagnosed FH within Stanford’s health records.

Using medical billing and lab data, the FH Foundation — Knowles is its chief medical officer — has developed a map to highlight the frequency of FH cases in the United States. Though imprecise, the map is intriguing, showing the condition is clustered on the East Coast, with a few notable exceptions such as a dense patch in eastern Oregon.

These efforts could improve current screening methods and allow affected families to obtain treatment and make life-extending changes in their diet and exercise patterns, the article states.

Previously: Big data used to help identify patients at risk of deadly high-cholesterol disorder, Could patients’ knowledge of their DNA lead to better outcomes? and Push-button personalized treatment guidance for patients not covered by clinical-trial results
Image by x6e38

Events, Public Health, Research, Science

What matters to Stanford’s Lucy Shapiro, and why

What matters to Stanford's Lucy Shapiro, and why

Shapiro getting National Medal of ScienceFasten your seatbelt: Developmental biologist Lucy Shapiro, PhD, is driving, and we’re zooming through her achievement-packed 40-year career in less than an hour.

Speaking this week as part of the “What Matters to Me and Why” series hosted by the Stanford Office of Religious Life, Shapiro said the topic prompted her to ponder why she was so passionate about the world of molecules and cells, a world invisible to most people.

To figure it out, Shapiro said she had to think back to when she was 13, applying for high schools. After consulting with her parents, Shapiro decided to apply for one of New York City’s elite public schools that focused on art and music. Unbeknownst to her parents, however, she decided she wasn’t going to take the exam in music as planned. Instead, she checked out a book on drawing from the library, taught herself to draw and passed the entrance exam by producing a portfolio of art.

These past 40 years have just been beautiful.

“That was really a defining moment. I learned I could change the trajectory of my own life by some action,” Shapiro said.

With that lesson firmly engrained — and with some well-timed assistance from mentors — Shapiro was off. There were detours, of course. Her senior college thesis was on Dante — interesting, Shapiro said, but “it didn’t make my heart sing.”

When prompted to go back to school and take an organic chemistry course, Shapiro discovered her true love.

“It sounds corny, but it was like the sky cleared. [Chemistry] was the most beautiful thing I had ever seen. It was clear that was how my mind worked,” Shapiro said.

She went on to make discoveries about the three-dimensional development of cells, compounds called RNA polymerases and many other advances in molecular biology, along the way mentoring scores of students and budding scientists. Her awards are numerous and include the prestigious National Medal of Science.

Now, she’s particularly passionate about the threat posed by pathogens, which are rapidly out-evolving the drugs available to rein them in. In response, she has helped found two pharmaceutical companies and is an active public speaker.

During her talk she offered numerous words of wisdom, including:

  • On discoveries: “It’s just indescribable when you discover something. It can be little, it doesn’t have to be earth-shattering. It is so exciting.”
  • On spirituality: “To me, science is religion. My love and passion for the scientific world is spiritual.”
  • On her career: “These past 40 years have just been beautiful. I still can’t wait to get into the lab each morning.”

There’s more. Much more. If you ever have the opportunity to hear her speak, I highly recommend it. It will be quite a ride.

Previously: Stanford scientist Lucy Shapiro: “It never occurred to me to question the things I wanted to do”, National Medal of Science winner Lucy Shapiro: “It’s the most exciting thing in the world to be a scientist” and Stanford’s Lucy Shapiro receives National Medal of Science
Photo of Shapiro accepting the National Medal of Science in 2013, courtesy of the White House

Biomed Bites, Infectious Disease, Microbiology, Research, Videos

Improving infection recovery

Improving infection recovery

Welcome to Biomed Bites, a weekly feature that introduces readers to some of Stanford’s most innovative biomedical researchers. 

Think back on the last time you came down with something. First you were sick, acutely ill. But then, days or hours later, you were no longer ill, but also not well, stuck in the grey zone of recovery.

That’s the stage of illness that most interests David Schneider, PhD, an associate professor of microbiology and immunology, and those in his lab. As Schneider explains in the video above:

It looks like recovery is a different sort of process than getting sick. So we’re trying to take this apart first by working with fruit flies, then by working with mice and eventually by working with people.

Our goal is to be able to take someone suffering from an infection and really help them improve their recovery.

Learn more about Stanford Medicine’s Biomedical Innovation Initiative and about other faculty leaders who are driving biomedical innovation here.

Previously: Immune cell linked to surgery recovery time, Stanford scientists find, Stanford team develops a method to prevent the viral infection that causes dengue fever and Shrugging off bugs: there’s more to beating infections than just fighting them

Bioengineering, Ethics, Genetics, In the News, Research, Science

Are at-home gene splicing kits a good idea? Stanford researchers weigh in

Are at-home gene splicing kits a good idea? Stanford researchers weigh in

chemist_stick_figure_by_wrpigeekAs demonstrated by the Foldscope, the uber-affordable microscope developed by Stanford bioengineer Manu Prakash, PhD — there is real fervor for bringing easy, do-it-yourself science to the masses. But what if that at-home science allows novices to dabble in some serious stuff, like splicing genes?

One Bay Area scientist has done just that: He’s marketing a $130 gene-editing kit that could bring the popular technology CRISPR into kitchens, basements and garages nationwide.

This particular kit isn’t particularly dangerous, according to a recent article in the San Jose Mercury News:

The kit has limited applications. His altered bacteria and yeast, quite harmless, lead brief and fairly dull lives. They can’t do much except change color, fragrance or live in inhospitable places. Then they die.

But two Stanford experts — infectious disease researcher David Relman, MD, and bioethicist Hank Greely, JD — agree it could place powerful technology in the hands of people who might not use it responsibly.

“I do not think that we want an unregulated, non-overseen community of freelance practitioners of this technology,” Relman told the Mercury News.

Regulation, or control, might not be possible, though, Greely cautioned. “You’ve got guys with B.S. degrees, in a garage,” he said in the article.

Kit developer Josiah Zayner doesn’t have a garage. But one version of the kit has already sold out.

Previously: CRISPR critters and CRISPR conundrums, Foldscope inventor named one of the world’s top innovators under 35 by Technology Review and Manu under the microscope
Image by WRPIgeek

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