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Wednesday, November 16th, 2016
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| 12:00a |
Data-driven diabetes management Diabetes is a growing epidemic in the United States. Now the seventh leading cause of death, the condition plagues more than an estimated 29 million Americans, according to the Centers for Disease Control and Prevention — and that number continues to rise.
But there’s another troubling issue: Research suggests many people with diabetes aren’t provided adequate resources to follow prescribed dose regimens, so they become “nonadherant,” which leads to serious health issues — and increased health care costs. A 2016 study in the American Journal of Managed Care found that patients with diabetes who are nonadherent spend about $2,700 more in medical costs per year than those who are adherent.
Now MIT spinout Common Sensing aims to solve the nation’s diabetes-management issues by going digital. The startup’s smart insulin-pen cap logs insulin intake data on an app and in the cloud, to help patients better manage their regimen. Moreover, the cap gives doctors a detailed view into patients’ insulin habits and how they affect blood-glucose levels, for more targeted care.
Invented by co-founders James White ’10, SM ’12 and Richard Whalley ’10, the Gocap is now going through clinical studies to test its viability. Most recently, Common Sensing, headquartered in Cambridge, Massachusetts, has partnered with the Joslin Diabetes Center in Boston, where it will collect data on 125 patients using the cap over the next year.
When Gocap finally hits the market, it will be provided to insurers, pharmaceutical companies, and provider and clinician networks, and be free for end users. “We really want these to be available, free of charge, to people that need them,” White says.
More confident dosing
Most diabetes patients use disposable insulin pens, which are adjusted for dosage and can be used numerous times before they’re empty. Each comes with a plastic cap that covers the injection needle.
When a patient uses a new pen, they replace the plastic cap with a Gocap, which uses an optical measurement method to measure the insulin volume in the pen. Each time the cap is removed and then replaced, it records the volume remaining and the time of the dose, which is displayed on a digital screen. Gocap also measures the temperature of the insulin, which can deteriorate at high temperatures. “We can alert people to the fact that they may be storing insulin too hot, which could seriously affect how they use it and how much effect it has on their body,” White says.
Gocap also has a digital component, where most of the tracking and analysis takes place. After each use, the device logs data from the pen via Bluetooth to a mobile app, and sends it to the cloud. On the app, patients can input information about glucose levels from their glucometer, their insulin type, and their meals.
In the cloud, patients can share the data with doctors or family members, who can track it in real time and provide interventions “at critical moments when people are dropping off medications,” White says. “If, say, my son or daughter sees I’ve dropped off from taking my insulin, they can give me a call and ask if I’m having difficulty using it.”
A doctor can use the data to tweak insulin dosage. People with diabetes usually get check-ups once every three to six months, where they provide a record of their glucose readings. The doctor may note high glucose readings over, say, a two-week period, and determine a patient needs more insulin. But that could have been due to missed doses, unbeknownst to the doctor or patient, which happens often, White says. With Gocap, the doctor can see those spikes are due to missed injections, meaning the doses are correct and prescribing more insulin could in fact be dangerous.
Additionally, the Gocap lets doctors watch insulin’s interaction with a person’s diet. They can then make targeted recommendations about, say, increasing dosage before eating certain meals. “Doctors may be afraid to do that otherwise, because if you take too much, you could end up in a coma or go to the hospital,” White says. “But if they can see exactly what’s going on, that gives them the confidence to recommend the correct amount of insulin.”
Making a win-win product
During their MIT years, White, a mechanical engineering student, and Whalley, a chemistry student, lived together in the Burton Connor building, and both harbored an interest in life sciences and medical technology. After they graduated, they moved into an apartment together while White finished his master’s degree and Whalley worked as a consultant for the biotech industry.
During that time, Whalley became aware of the lack of data in diabetes management, and White was working on new injection methods in the lab of Department of Mechanical Engineering Professor Ian Hunter, where he learned about insulin-adherence issues. When the MIT Media Lab’s 2012 Health and Wellness Innovation hackathon rolled around, the duo built a Gocap prototype — a bulky mess of wires — in their apartment’s kitchen. With that prototype, they launched Common Sensing, in Industry Lab, a co-working space in Cambridge.
Early on, the startup reached out to mentors at MIT, including the Entrepreneurs in Residence at the Martin Trust Center for MIT Entrepreneurship and the MIT Venture Mentoring Service. Among other things, White says, mentors taught them how to ask the right questions. For instance, in the medical device industry, he says, there are many stakeholders with different incentives — the medical device makers, the end users, the insurance providers, the doctors, the hospitals, the pharmaceutical companies, and potentially the government. “The most important question we asked through this process is, ‘How do we make this a product where all those stakeholders can win?’” White says.
To answer that question, Common Sensing has run Gocap through numerous studies, involving, in total, more than 200 diabetes patients. In the last 18 months, the startup has also provided the device to pharmaceutical companies and doctors to gather feedback.
These studies have led to a few redesigns of the product, including changes involving what information to put on the device’s screen, and what needs to be sent to the cloud. “For every design decision, there is a wealth of user experience research to back it up,” White says.
Planned future studies, White says, will investigate the cost of various interventions strategies for users who’ve dropped off their insulin regimen, such as free text messaging or, for pennies more, a phone-based service. “These are the kinds of moments I’m most excited about,” White says. “Because then you can identify who is having the most issues and coach them, which empowers the user to be healthier, saves money for insurance companies, and makes sure pharmaceutical products are being used properly. It’s a win-win for everyone.” | | 12:59p |
Pluto’s icy, slushy heart Beneath Pluto’s “heart” lies a cold, slushy ocean of water ice, according to data from NASA’s New Horizons mission. In a paper published today in the journal Nature, the New Horizons team, including researchers from MIT, reports that the dwarf planet’s most prominent surface feature — a heart-shaped region named Tombaugh Regio — may harbor a bulging, viscous, liquid ocean just below its surface.
The existence of a subsurface ocean may solve a longstanding puzzle: For decades, astronomers have observed that Tombaugh Regio, which is Pluto’s brightest region, aligns almost exactly opposite from the dwarf planet’s moon, Charon, in a locked orientation that has lacked a convincing explanation.
A thick, heavy ocean, the new data suggest, may have served as a “gravitational anomaly,” or weight, which would factor heavily in Pluto and Charon’s gravitational tug-of-war. Over millions of years, the planet would have spun around, aligning its subsurface ocean and the heart-shaped region above it, almost exactly opposite along the line connecting Pluto and Charon.
“Pluto is hard to fathom on so many different levels,” says New Horizons co-investigator Richard Binzel, professor of earth, atmospheric and planetary sciences at MIT. Binzel is also a joint professor of aerospace engineering and a faculty affiliate with the MIT Kavli Institute. “People had considered whether you could get a subsurface layer of water somewhere on Pluto. What’s surprising is that we would have any information from a flyby that would give a compelling argument as to why there might be a subsurface ocean there. Pluto just continues to surprise us.”
Features from a flyby
On Jan. 19, 2006, New Horizons, a spacecraft about the size of a baby grand piano, launched from Cape Canaveral, Florida, on a nine-year journey to the solar system’s distant dwarf planet. On July 14, 2015, the probe approached Pluto and spent the next three months observing its surface before completing the flyby and continuing on to the Kuiper belt.
During its flyby of Pluto, New Horizons collected measurements of surface features, including the dimensions of Pluto’s bright, heart-shaped region. In particular, the spacecraft focused on a circular region in its left “ventricle,” named Sputnik Planitia, which is thought to be a giant impact basin. From the probe’s measurements, Binzel and his colleagues determined the size and depth of Sputnik Planitia.
“It’s similar in proportional size to the largest basins on Mercury and Mars,” Binzel says.
The researchers determined that the heart-shaped region, and Sputnik Planitia in particular, is aligned almost exactly opposite from Charon.
“The New Horizons data say it’s not only opposite Charon, but it’s really close to being almost exactly opposite,” Binzel says. “So we asked, what’s the chance of that randomly happening? And it’s less than 5 percent that it would be so perfectly opposite. And then the question becomes, what was it that caused this alignment?”
A viscous ocean
The massive basin also appears extremely bright relative to the rest of the planet, and the reason, the New Horizons data suggest, is that it is filled with frozen nitrogen ice.
Previously, Binzel and the New Horizons team had found evidence that this liquid nitrogen may be constantly refreshing, or convecting, as a result of a weak spot at the bottom of the basin. This weak spot may let heat rise through Pluto’s interior to continuously convect the ice, bubbling it over “like boiling oatmeal,” Binzel says.
To the New Horizons team, a weak spot in Sputnik Planitia’s basin suggests that the planet’s crust, particularly in this region, must be quite thin. If a massive impactor indeed created the basin, it may have also triggered any material beneath the surface to push the thin crust outward, causing a “positive gravitational anomaly,” or a thick, heavy mass, that would have helped to align the region relative to Charon.
But what sort of material would create enough of a gravitational weight to reorient the planet relative to its moon? To answer this, the team turned to a geophysical model of Pluto’s interior, working in measurements from the New Horizons spacecraft.
“Pluto is small enough that it’s just about almost cooled off but still has a little heat, and it’s about 2 percent the heat budget of the Earth, in terms of how much energy is coming out,” Binzel says. “So we calculated Pluto’s size with its interior heat flow, and found that underneath Sputnik Planitia, at those temperatures and pressures, you could have a zone of water-ice that could be at least viscous. It’s not a liquid, flowing ocean, but maybe slushy. And we found this explanation was the only way to put the puzzle together that seems to make any sense.”
Lindy Elkins-Tanton, director of the School of Earth and Space Exploration at Arizona State University, says the team’s results for Pluto may have implications for planetary bodies further out in the solar system.
“A few researchers have thought Pluto could retain enough heat to still be warm, but it’s been a minority opinion — most people thought Pluto must be cold by now! So an ocean is a very welcome and extremely interesting result,” says Elkins-Tanton, who did not contribute to the paper. “The surprises of Pluto raise the possibility that other Kuiper Belt objects may also still be warm. These results immediately put large Kuiper belt objects on the list of places that could harbor life. What a great surprise!”
An icy heart
In addition to being aligned with Charon, Pluto’s heart lies almost exactly at the equator — a location which Binzel’s graduate student and co-author Alissa Earle has found may have helped the region keep its alignment with Charon locked firmly in place.
In a separate paper that was published online in September in the journal Icarus, Earle modeled Pluto’s surface temperatures over millions of years and found that while the poles experience wild swings in temperature, with long frigid winters and equally long, hot summers, the equator has more moderate temperatures. That’s because it cycles through daytime and nighttime fairly regularly, every three days.
Earle found that if bright ice builds up at the poles, it simply melts away when summer returns. But if that same ice forms near the equator, it never gets warm enough to melt away.
“What makes the equator unique is, if you put a bright spot there, because it never gets too hot or cold, then the bright spot will always stay cold,” Earle says. “If ice accumulates at the equator, it can hang onto it.”
Earle modeled the region’s temperatures over millions of years, looking at the tilt of Pluto’s axis, its orientation to the sun, and its daily rotation. From all this, she found that Sputnik Planitia’s ice sheet likely has persisted for millions of years. The long-lived deposit of ice on Pluto’s “heart” may have also played a role in orienting the planet toward its moon.
“This basin probably has been there a long time and had this bright ice spot for a very long time,” Earl says. “And that may have helped to get it rotated to where it is today.”
This research was funded, in part, by NASA. | | 2:02p |
New capsule achieves long-term drug delivery Researchers at MIT and Brigham and Women’s Hospital have developed a new drug capsule that remains in the stomach for up to two weeks after being swallowed, gradually releasing its drug payload. This type of drug delivery could replace inconvenient regimens that require repeated doses, which would help to overcome one of the major obstacles to treating and potentially eliminating diseases such as malaria.
In a study described in the Nov. 16 issue of Science Translational Medicine, the researchers used this approach to deliver a drug called ivermectin, which they believe could aid in malaria elimination efforts. However, this approach could be applicable to many other diseases, says Robert Langer, the David H. Koch Institute Professor at MIT and a member of MIT’s Koch Institute for Integrative Cancer Research.
“Until now, oral drugs would almost never last for more than a day,” Langer says. “This really opens the door to ultra-long-lasting oral systems, which could have an effect on all kinds of diseases, such as Alzheimer’s or mental health disorders. There are a lot of exciting things this could someday enable.”
Langer and Giovanni Traverso, a research affiliate at the Koch Institute and a gastroenterologist and biomedical engineer at Brigham and Women’s Hospital, are the senior authors of the paper. The paper’s lead authors are former MIT postdoc Andrew Bellinger, MIT postdoc Mousa Jafari, and former MIT postdocs Tyler Grant and Shiyi Zhang. The team also includes researchers from Harvard University, Imperial College London, and the Institute for Disease Modeling in Bellevue, Washington.
The research has led to the launching of Lyndra, a Cambridge-based company that is developing the technology with a focus on diseases for which patients would benefit the most from sustained drug delivery, including neuropsychiatric disorders, HIV, diabetes, and epilepsy.
Long-term delivery
Drugs taken orally tend to work for a limited time because they pass rapidly through the body and are exposed to harsh environments in the stomach and intestines. Langer’s lab has been working for several years to overcome this challenge, with an initial focus on malaria and ivermectin, which kills any mosquito that bites a person who is taking the drug. This can greatly reduce the transmission of malaria and other mosquito-borne illnesses.
The team envisions that long-term delivery of ivermectin could help with malaria elimination campaigns based on mass drug administration — the treatment of an entire population, whether infected or not, in an area where a disease is common. In this scenario, ivermectin would be paired with the antimalaria drug artemisinin.
“Getting patients to take medicine day after day after day is really challenging,” says Bellinger, now a cardiologist at Brigham and Women’s Hospital and chief scientific officer at Lyndra. “If the medicine could be effective for a long period of time, you could radically improve the efficacy of your mass drug administration campaigns.”
To achieve ultra-long-term delivery, drugs need to be packaged in a capsule that is stable enough to survive the harsh environment of the stomach and can release its contents over time. Once the drug is released, the capsule must break down and pass safely through the digestive tract.
Working with those criteria in mind, the team designed a star-shaped structure with six arms that can be folded inward and encased in a smooth capsule. Drug molecules are loaded into the arms, which are made of a rigid polymer called polycaprolactone. Each arm is attached to a rubber-like core by a linker that is designed to eventually break down.
After the capsule is swallowed, acid in the stomach dissolves the outer layer of the capsule, allowing the six arms to unfold. Once the star expands, it is large enough to stay in the stomach and resist the forces that would normally push an object further down the digestive tract. However, it is not large enough to cause any harmful blockage of the digestive tract.
“When the star opens up inside the stomach, it stays inside the stomach for the duration that you need,” says Grant, now a product development engineer at Lyndra.
In tests in pigs, the researchers confirmed that the drug is gradually released over two weeks. The linkers that join the arms to the core then dissolve, allowing the arms to break off. The pieces are small enough that they can pass harmlessly through the digestive tract.
“This is a platform into which you can incorporate any drug,” Jafari says. “This can be used with any drug that requires frequent dosing. We can replace that dosing with a single administration.”
This type of delivery could also help doctors to run better clinical trials by making it easier for patients to take the drugs, Zhang says. “It may help doctors and the pharma industry to better evaluate the efficacy of certain drugs, because currently a lot of patients in clinical trials have serious medication adherence problems that will mislead the clinical studies,” he says.
Amplified effects
The new study includes mathematical modeling done by researchers at Imperial College London and the Institute for Disease Modeling to predict the potential impact of this approach. The models suggest that if this technology were used to deliver ivermectin along with antimalaria treatments to 70 percent of a population in a mass drug administration campaign, disease transmission could be reduced the same amount as if 90 percent were treated with antimalaria treatments alone.
“What we showed is that we stand to significantly amplify the effect of those campaigns,” Traverso says. “The introduction of this kind of system could have a substantial impact on the fight against malaria and transform clinical care in general by ensuring patients receive their medication.”
Peter Agre, director of the Johns Hopkins Malaria Research Institute, who was not involved in the research, described the new approach as a “remarkable” advance that could improve treatment of malaria and any other disease that requires long-term treatment.
“If you could reduce the frequency of dosing, and one treatment would continue to release medicine until the course is completed, that would be very beneficial,” Agre says.
Researchers led by Traverso are working on developing similar capsules to deliver drugs against other tropical diseases, as well as HIV and tuberculosis.
The research was funded by the Bill and Melinda Gates Foundation, the National Institutes of Health, and the Max Planck Research Award. | | 4:00p |
Seeking to inform India’s climate policy choices The MIT Energy Initiative is sharing reports from the United Nations Climate Change Conference in Marrakech, Morocco, where MIT community members are observing the climate negotiations and speaking at auxiliary events.
At a side event of COP22, the 2016 United Nations Climate Change Conference in Marrakech, Morocco, researchers and nongovernmental leaders from around the world discussed policy research that can support implementation of the 2015 Paris Agreement to limit global temperature rise. Among the nine panelists was a sole graduate student: MIT’s Arun Singh.
On the panel, “New Directions in Climate Change Research and Implications for Policy,” Singh and fellow representatives of the COP22 Research and Independent Nongovernmental Organizations (RINGO) constituency gave brief overviews of their research in various areas, from agro-industrial development policies to green social work.
Singh shared his research on clean development pathways for India, which applies an energy-economic model he is developing with advisors Valerie Karplus and Niven Winchester. The model simulates policy and technology choices India could make to fulfill its intended, nationally determined contributions under the Paris Agreement — and how each of those choices could impact emissions, energy use, and the country’s economy.
“For example,” says Singh, “how would India’s ambitious solar targets compare with, say, a price on carbon to achieve similar levels of emissions reductions? Who wins and loses under alternate policy choices? Those are the types of questions we’re looking to answer.”
In the global effort to address climate change, India’s role as a major player is indisputable. The country is the third largest emitter of global greenhouse gas emissions, behind China and the U.S., yet nearly 19 percent of India’s population, most of which lives in rural areas, still lacks reliable access to electricity — and the population is still growing rapidly.
“India is in a situation where it has to balance tradeoffs between increasing energy output and ensuring that additional generation does not add significantly to the country’s carbon emissions,” Singh explains. To make these tradeoffs, policymakers and regulators would benefit from having access to quantitative analysis of policy impacts, which Singh and his team hope to provide.
“Arun’s work stands out because it combines modeling of policies at the country level with an assessment of financial and operational barriers to clean energy investment at the micro level,” says Karplus, an assistant professor of global economics and management at the MIT Sloan School of Management, who is also a faculty affiliate of the MIT Energy Initiative and the Joint Program on the Science and Policy of Global Change. “We hope to work with policymakers in India to identify strategies that are cost effective and politically workable. To do that, we need to analyze proposals in terms of both the cost and the distribution of impacts.”
For Singh, researching solutions to climate and energy issues is personal: Having grown up in Ayodhya, India, he experienced the challenges firsthand. “Frequent power cuts were a norm while I was growing up. In peak summer months, we would not get power for eight to 10 hours a day. And this was still in a town,” he says.
Following his undergraduate studies at India Institute of Technology Roorkee, Singh became more interested in understanding energy and environmental policymaking, while working at a petroleum refinery. Then, as a research associate at the Abdul Latif Jameel Poverty Action Lab (J-PAL) South Asia office in Mumbai, he worked on environmental regulation reform projects in India, including a pilot emissions trading scheme for industrial particulate matter emissions, conducted with India’s Ministry of Environment and Forests. At J-PAL, he also carried out an impact evaluation of public disclosure of industrial air pollution ratings, for which he analyzed emissions data from more than 5,000 firms and worked closely with his team and with regulators to secure approval for a new disclosure program.
As he made field visits to some of the most polluted industrial clusters in India, he learned how nuanced the issues can be. “In India it is common to hold strong positions favoring or opposing development. But that’s not helpful, as it’s not an either-or question,” he says. “Smart policies can be designed that encourage growth while limiting the impact on natural environment and climate. And India already has several forward-looking policies in place.”
His work motivated him to come to MIT, where he arrived with a desire to focus on climate and energy policy research for developing countries, but he was not yet sure exactly where his studies would take him.
He started in 2015 as a graduate student in the Technology and Policy Program — which is now part of the Institute for Data Systems and Society — working with Karplus to study policies and regulation in the electricity sector in India, with funding from the MIT Energy Initiative. Then, an opportunity arose to help Karplus and Winchester develop the energy-economic model he now works on as a fellow of the Tata Center for Technology and Design and research assistant in the MIT Joint Program.
When Karplus learned of a call for researchers to present at COP22 with the RINGO constituency, she alerted Singh, who applied and was selected to present.
In Marrakech, Singh shared preliminary findings from his model, which offer initial insights into how carbon pricing and renewable energy support policies compare in terms of their impact on carbon dioxide emissions, the energy system, and the economy. To finalize his research, he plans to expand the model’s specifications to reflect policy priorities and physical constraints, especially on details in technology choices. He is also investigating the political and economic factors that drive these choices, and viable design options for increasing the political feasibility of cost-effective policies to reduce carbon dioxide emissions.
While at COP22, Singh also had the opportunity to interview developers, investors, and aid organizations that are involved in the expansion of renewable energy in Morocco, supporting Karplus as she contributes to an upcoming book on the commercialization of renewable energy in several African countries.
“I am so pleased and proud that Arun had the opportunity to represent our group in Marrakech. By interacting with diverse stakeholders at the COP, Arun has been able to share his research on India with the world, and compare and contrast its insights with experiences in other countries,” Karplus says.
At MIT, Singh co-leads a student group, Energy for Human Development (e4Dev), with fellow graduate student Turner Cotterman, bringing together members of the MIT community to advance understanding of issues facing the developing world, with guest lectures from notable experts, outreach programs, and educational opportunities. He plans to share his COP22 experience with the group.
Singh’s first experience with UN climate negotiations has been “overwhelming,” he says, from the efforts that go into organizing the COP to how the complex negotiation process functions.
“It’s very encouraging to see enthusiastic participation of all countries and the near unanimous recognition of climate change as a problem requiring strong collective efforts,” he says. “There’s no room for skepticism or delaying action.”
Singh looks forward to continuing to play a role in informing energy and climate solutions for India with his research, as part of the MIT community dedicated to making a better world. |
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