Helping companies navigate Covid-19

In his new book “The New (Ab)Normal: Reshaping Business and Supply Chain Strategy Beyond Covid-19,” published today, MIT Professor Yossi Sheffi explains how companies grappled with the chaos of the Covid-19 pandemic and how they can survive and thrive as the crisis subsides. Sheffi pays particular attention to supply chains’ role in helping companies manage and recover from the pandemic.

“Much has been written about the pandemic, but the book takes a different perspective by showing how the virus emphasizes our interconnectedness and how supply chains are the connective tissue that is vital to the health of a vibrant society,” says Sheffi, the director of the MIT Center for Transportation and Logistics.

The book begins with an account of the struggle to mend the global economic fabric as the coronavirus ripped more holes in it. By viewing the crisis through a risk-management lens derived from Sheffi’s previous books, “The Resilient Enterprise” and “The Power of Resilience,” the author shows how companies create corporate immune systems to recognize and manage large-scale disruptions quickly.

Having set the scene, Sheffi describes the emergence of a “new normal” where phenomena such as business safe zones that protect customers and workers from the contagion and the rise of telecommuting redefine daily life. The new normal reshapes supply chains as well. For example, the acceleration of technology trends during the crisis could profoundly influence the future performance of supply chains, argues Sheffi.

He also explores broader changes wrought by Covid-19. An example is how the pandemic affirms supply chains’ critically important societal role. Civilization depends on supply chains to convert the planet’s bounty into needed products and deliver those products to 7.8 billion human beings at an affordable price. Sheffi shows that contrary to many media headlines, supply chains performed heroically during the pandemic and maintained supplies of critical products such as food. Yet, he acknowledges that there were failures and offers prescriptions for avoiding future breakdowns in health-care supplies.

The book ends with a look at the post-pandemic future — and the outlook is not necessarily gloomy. For instance, technological advances inspired by the crisis could level the playing field between small and large companies. Nimble small businesses can use a growing array of off-the-shelf cloud computing and mobile apps to narrow the competitive gap between themselves and larger rivals.

An essential lesson from the crisis is that flexibility and agility are critical to managing the pandemic’s disruptions and the pivot towards a changed future.

Supply chains will be at the core of the recovery. As “The New (Ab)Normal” highlights, supply chains served humanity during this global crisis and will continue to do so when the pandemic subsides, and beyond.

“One of my key objectives in writing the book is to help executives adapt their business models and supply chains to a world transformed by Covid-19,” says Sheffi.

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How contact tracing happens at MIT

Contact tracing is an essential tool for fighting the Covid-19 pandemic: If someone tests positive for the virus, health care workers move quickly to determine who else the infected individual had close contact with, and to set up measures to keep the virus from potentially spreading further. Yet while contact tracing has been a much-repeated phrase during the pandemic, people in the MIT community and beyond may wonder: How does the system actually work on the Institute’s campus?

As it happens, MIT runs its own swift-moving contact tracing program through MIT Medical, the campus’ health center — which delivers test results and exposure information to individuals affected by positive cases, and helps them chart their next steps as they quarantine.

“It allows for us to help the community very quickly, get notifications out, and give support to individuals,” says Shawn Ferullo, associate medical director and chief of student health at MIT Medical. Ferullo, Nurse Practitioner Jacqueline Sherry, and Nurse Practice Manager Maura Rowley have been leading MIT’s contact tracing program.

In handling this process during the Covid-19 pandemic, MIT Medical’s team members are drawing on years of contact tracing experience, applied to limit the spread of chicken pox, measles, mumps, tuberculosis, and other infectious diseases. Sherry, who specializes in occupational medicine and infectious diseases, has also developed a long-running relationship with the Cambridge, Massachusetts Department of Public Health, which ultimately oversees regulations and procedures for the city.

That know-how has helped MIT Medical set up a contact tracing program for Covid-19 with high priority on immediate action.

“Contact tracing work is today’s work today,” Ferullo notes. “This isn’t, ‘Oh, it’s 5:00 p.m., we’ll get to it tomorrow.’ The work day doesn’t end until the work is completed.”

Action after positive tests

So far 39 members of the MIT community have tested positive for Covid-19, based on the tests administered by MIT since August. The Institute tests MIT students, faculty, and staff at regular intervals on campus. Community members can also get tested if they are experiencing Covid-like symptoms.

The MIT tests are collected at one of MIT Medical’s testing sites and are processed at the Broad Institute. Depending on the reason for the test, community members receive test results via either the Covid Pass app (where they also enter their daily health attestations and get reminders for routine campus testing); or MIT Medical’s electronic medical record patient portal, if the test was performed as part of a clinical care visit.

When a positive result occurs, a small number of MIT Medical personnel are notified, and one of them quickly contacts the individual in question by phone. If the patient does not pick up, a non-specific message is left via voicemail — and, in some cases, email — urging them to contact MIT Medical right away.

“Step number one is always notifying the person who has the result, so they’re aware right away and know they should isolate,” Ferullo says. “We [want to] catch them before they go in to work, or before they go to class. Some of that call is support for that individual too.” When people test positive, he adds, they usually ask: “‘What does this mean? How did I get this?’ There’s a little bit of helping them digest the result, [asking if they] live with family members, and how can we help them. That call happens right away.”

People testing positive must then enter into a period of isolation for a minimum of 10 days, rigorously limiting contact with other people.

At the same time, MIT Medical’s contact tracing team also works with the individual who has tested positive, to trace their recent activities and identify any close contact with other community members. That information sparks a second round of phone calls: The MIT Medical team then talks to the people (if there are any) who may have been exposed to the virus by the Covid-positive individual.

If that level of contact was significant enough, the exposed individuals also have to enter into a 14-day quarantine. For these people — who do not know if they have contracted the virus — MIT Medical recommends that they have a Covid-19 test approximately five to seven days from the time of contact, when about 99 percent of people carrying the virus will test positive. Even if that day 7 test is negative, though, people still must observe quarantine for 14 days, by state regulations.

When people must quarantine due to exposure to a positive-testing individual, MIT Medical staff will give them direction to help figure out the logistics, just as the staff will work with people who have tested positive.

“We talk them through what it means for them, and offer them that same support, all the appropriate guidance,” Ferullo says.

MIT Medical strictly follows all privacy regulations: When communicating with people who may have been exposed, they do not disclose the name of the individual who tested positive. Through all of this, speed is essential.

“We had someone who tested at 10:30 in the morning, we got their positive result from Broad at 5:30 in the evening, and by 6:30 all the contacts were done and all the notifications of other individuals were done,” Ferullo says. The faster people can begin quarantining, the lower the transmission rate in the community, in all likelihood.

Additionally, once the positive individual has been notified and their contacts have been established, the contact tracing team reviews the spaces on campus that had been used by the positive individual in the previous 48 hours.

“We recognize that contact tracing is first and foremost about the notification of the individual, identifying any people with whom they have had close contact, and then considering the space that had been used,” Ferullo says.

Through close partnership with campus partners in MIT Emergency Management; the Environment, Health, and Safety Office; Custodial Services; and MIT Facilities, the contact tracing team establishes details about spaces that require a rapid, efficient cleaning, as per the Institute’s Covid protocols. The identity of the positive individual is again kept private during this process, while the needs assessment is shared and the cleaning is done.

Continued support

MIT Medical has built layers into their contact tracing team, and has trained more staff to be activated to help to handle contact tracing, should the MIT case load increase. So far, only the core team has been called into action. But all of them are ready if needed.

Contact tracing can be labor-intensive: When people test positive, the contact tracing team will follow up with those individuals the next day by phone, and do the same for people who have had close contact with them.

“We do that so we can continue to offer them support, recognizing that oftentimes people will hang up and then think of questions they couldn’t think of in the moment,” Ferullo says. “I feel we can do it in a way that we can really support our community members. You don’t want people to hang up that phone and then think, ‘Now what?’”

So far, Ferullo notes, “The biggest challenge sometimes is reaching individuals, if they don’t answer their phone or have voicemail set up.” In those cases, staff will send emails to community members, asking them to answer their phones if MIT Medical calls. Due to privacy regulations, MIT Medical does not disclose substantive information in emails.

At the same time, Ferullo praises the attitude the MIT community has taken during the pandemic, noting how much efforts to contain the virus are helped by strict adherence to safety protocols.

“I will say, when you’re doing contact tracing, you realize the power of physical distancing and mask policies,” Ferullo says. “The best [cases] are when people have zero close contact, because they did all the right things. … I think what we see is how those policies quickly feed into controlling spread of the virus.”

Ultimately, he notes, MIT Medical’s goal is to serve people, and their complex needs, at a time when the Covid-19 pandemic has already complicated daily life.

“Every case is different,” Ferullo says. “Because every person is different, every life is different. Who has young kids at home? Who cares for their elderly parents who live with them? Who needs to be in a lab? Who lives in a dorm room by themselves? So each case has a flavor of the same, but they’re all very different. We see our role as not just notifying and manging, but supporting and helping navigate, too. I think we’re trying to do all those things at the same time for the community.”

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Pablo Jarillo-Herrero wins 2020 Spanish Royal Physics Society Medal

Pablo Jarillo-Herrero, the Cecil and Ida Green Professor of Physics, was honored with the highest scientific recognition of the Spanish Royal Physics Society (RSEF) for his pioneering experimental work on “twistronics,” a promising technique for adjusting the electronic properties of graphene by rotating adjacent layers of the material.  

The RSEF medal recognizes Jarillo-Herrero’s “exceptional and groundbreaking work on twisted heterostructures (graphene on hBN and twisted bilayer graphene) and, specifically, his discovery of correlated insulating behavior and unconventional superconductivity in magic-angle graphene superlattices,” according to the RSEF release. “These remarkable discoveries have constituted the beginning of a completely new field: strongly correlated physics in 2D Moiré superlattices.”

He will receive a commemorative medal and a cash award of 15,000 euros (about $17,700) in an upcoming ceremony to be led by RSEF President José Adolfo de Azcárraga. Financially supported by the BBVA Foundation, the annual RSEF Physics Prizes are awarded to Spanish nationals or to scientists of any nationality working in Spain.  

"It is always humbling to receive an award, and in this case I'm particularly happy because the recognition comes from distinguished fellow Spanish colleagues,” says Jarillo-Herrero. “I hope this will serve as inspiration to many young people to pursue their interests in science."

Jarillo-Herrero's research interests lie in the area of experimental condensed matter physics, in particular quantum electronic transport and optoelectronics in novel two-dimensional materials, with special emphasis on investigating their superconducting, magnetic, and topological properties.

The Jarillo-Herrero Group explores quantum transport in novel condensed matter systems such as graphene and topological insulators. The group has expanded research into the electronic properties of two-dimensional graphene, an effective electrical conductor, into what has been dubbed “twistronics.”

Such research studies show how to "tune" the electronic properties of two-dimensional materials by changing, or "twisting," the angle of rotation between two adjacent crystalline layers of graphene. This is a major finding in quantum materials research. By creating and measuring bilayer graphene of multiple twist angles, Jarillo-Herrero's group in 2018 discovered “the magic angle” — two layers positioned at 1.1 degrees — that produced unpredicted electronic behaviors. At this "magic angle," and at low temperatures, electrons in twisted bilayer graphene were seen to slow down tremendously, and that’s where Jarillo-Herrero’s group discovered new areas such as novel insulating and superconducting states.

The new field of twistronics is expected to influence multiple areas of science and technology, including  the design of new superconductors, and the development of novel quantum devices for advanced quantum sensing, photonics, and computing applications. 

A native of Valencia, Spain, Jarillo-Herrero received his licenciatura in physics from the University of Valencia, Spain, his MS degree from the University of California at San Diego, and his PhD at the Delft University of Technology in the Netherlands. He was a NanoResearch Initiative Fellow at Columbia University, and then joined MIT as an assistant professor of physics in 2008, where he received tenure in 2015, and was promoted to full professor of physics in 2018.

His awards include an Alfred P. Sloan Fellowship; a David and Lucile Packard Fellowship; a DoE Early Career Award; a Presidential Early Career Award for Scientists and Engineers; an ONR Young Investigator Award; a Moore Foundation Experimental Physics in Quantum Systems Investigator Award; The Physics World 2018 Breakthrough of the Year; the 2020 Oliver E. Buckley Condensed Matter Physics Prize; and the 2020 Wolf Prize in Physics. In 2018, Jarillo-Herrero was elected a fellow of the American Physical Society.   

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Cancer researchers collaborate, target DNA damage repair pathways for cancer therapy

Cancer therapies that target specific molecular defects arising from mutations in tumor cells are currently the focus of much anticancer drug development. However, due to the absence of good targets and to the genetic variation in tumors, platinum-based chemotherapies are still the mainstay in the treatment of many cancers, including those that have a mutated version of the tumor suppressor gene p53. P53 is mutated in a majority of cancers, which enables tumor cells to develop resistance to platinum-based chemotherapies. But these defects can still be exploited to selectively target tumor cells by targeting a second gene to take down the tumor cell, leveraging a phenomenon known as synthetic lethality.

Focused on understanding and targeting cell signaling in cancer, the laboratory of Michael Yaffe, the David H. Koch Professor Science and director of the MIT Center for Precision Cancer Medicine, seeks to identify pathways that are synthetic lethal with each other, and to develop therapeutic strategies that capitalize on that relationship. His group has already identified MK2 as a key signaling pathway in cancer and a partner to p53 in a synthetic lethal combination.

Now, working with a team of fellow researchers at MIT’s Koch Institute for Integrative Cancer Research, Yaffe’s lab added a new target, the gene XPA, to the combination. Appearing in Nature Communications, the work demonstrates the potential of “augmented synthetic lethality,” where depletion of a third gene product enhances a combination of targets already known to show synthetic lethality. Their work not only demonstrates the effectiveness of teaming up cancer targets, but also of the collaborative teamwork for which the Koch Institute is known.

P53 serves two functions: first, to give cells time to repair DNA damage by pausing cell division, and second, to induce cell death if DNA damage is too severe. Platinum-based chemotherapies work by inducing enough DNA damage to initiate the cell’s self-destruct mechanism. In their previous work, the Yaffe lab found that when cancer cells lose p53, they can re-wire their signaling circuitry to recruit MK2 as a backup pathway. However, MK2 only restores the ability to orchestrate DNA damage repair, but not to initiate cell death.

The Yaffe group reasoned that targeting MK2, which is only recruited when p53 function is absent, would be a unique way to create a synthetic lethality that specifically kills p53-defective tumors, by blocking their ability to coordinate DNA repair after chemotherapy. Indeed, the Yaffe Lab was able to show in pre-clinical models of non-small cell lung cancer tumors with mutations in p53, that silencing MK2 in combination with chemotherapy treatment caused the tumors to shrink significantly.

Although promising, MK2 has proven difficult to drug. Attempts to create target-specific, clinically viable small-molecule MK2 inhibitors have so far been unsuccessful. Researchers led by co-lead author Yi Wen Kong, then a postdoc in the Yaffe lab, have been exploring the use of RNA interference (siRNA) to stop expression of the MK2 gene, but siRNA’s tendency to degrade rapidly in the body presents new challenges.

Enter the potential of nanomaterials, and a team of nanotechnology experts in the laboratory of Paula Hammond, the David H. Koch Professor of Engineering, head of the MIT Department of Chemical Engineering, and the Yaffe group’s upstairs neighbor. There, Kong found a willing collaborator in then-postdoc Erik Dreaden, whose team had developed a delivery vehicle known as a nanoplex to protect siRNA until it gets to a cancer cell. In studies of non-small cell lung cancer models where mice were given the MK2-targeting nanocomplexes and standard chemotherapy, the combination clearly enhanced tumor cell response to chemotherapy. However, the overall increase in survival was significant, but relatively modest.

Meanwhile, Kong had identified XPA, a key protein involved in another DNA repair pathway called NER, as a potential addition to the MK2-p53 synthetic lethal combination. As with MK2, efforts to target XPA using traditional small-molecule drugs have not yet proven successful, and RNA interference emerged as the team’s tool of choice. The flexible and highly controllable nature of the Hammond group’s nanomaterials assembly technologies allowed Dreaden to incorporate siRNAs against both XPA and MK2 into the nanocomplexes.

Kong and Dreaden tested these dual-targeted nanocomplexes against established tumors in an immunocompetent, aggressive lung cancer model developed in collaboration between the laboratories of professor of biology Michael Hemann and Koch Institute Director Tyler Jacks. They let the tumors grow even larger before treatment than they had in their previous study, thus raising the bar for therapeutic intervention.

Tumors in mice treated with the dual-targeted nanocomplexes and chemotherapy were reduced by up to 20-fold over chemotherapy alone, and similarly improved over single-target nanocomplexes and chemotherapy. Mice treated with this regimen survived three times longer than with chemotherapy alone, and much longer than mice receiving nanocomplexes targeting MK2 or XPA alone.

Overall, these data demonstrate that identification and therapeutic targeting of augmented synthetic lethal relationships — in this case between p53, MK2 and XPA — can produce a safe and highly effective cancer therapy by re-wiring multiple DNA damage response pathways, the systemic inhibition of which may otherwise be toxic.

The nanocomplexes are modular and can be adapted to carry other siRNA combinations or for use against other cancers in which this augmented synthetic lethality combination is relevant. Beyond application in lung cancer, the researchers — including Kong, who is now a research scientist at the Koch Institute, and Dreaden, who is now an assistant professor at Georgia Tech and Emory School of Medicine — are working to test this strategy for use against ovarian and other cancers.

Additional collaborations and contributions were made to this project by the laboratories of Koch Institute members Stephen Lippard and Omer Yilmaz, the Eisen and Chang Career Development Professor. 

This work was supported in part by a Mazumdar-Shaw International Oncology Fellowship, a postdoctoral fellowship from the S. Leslie Misrock (1949) Frontier Fund for Cancer Nanotechnology, and by the Charles and Marjorie Holloway Foundation, the Ovarian Cancer Research Foundation, and the Breast Cancer Alliance.

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SMART researchers receive Intra-CREATE grant for personalized medicine and cell therapy

Researchers from Critical Analytics for Manufacturing Personalized-Medicine (CAMP), an interdisciplinary research group at Singapore-MIT Alliance for Research and Technology (SMART), MIT’s research enterprise in Singapore, have been awarded Intra-CREATE grants from the National Research Foundation (NRF) Singapore to help support research on retinal biometrics for glaucoma progression and neural cell implantation therapy for spinal cord injuries. The grants are part of the NRF’s initiative to bring together researchers from Campus for Research Excellence And Technological Enterprise (CREATE) partner institutions, in order to achieve greater impact from collaborative research efforts.

SMART CAMP was formed in 2019 to focus on ways to produce living cells as medicine delivered to humans to treat a range of illnesses and medical conditions, including tissue degenerative diseases, cancer, and autoimmune disorders.

“Singapore’s well-established biopharmaceutical ecosystem brings with it a thriving research ecosystem that is supported by skilled talents and strong manufacturing capabilities. We are excited to collaborate with our partners in Singapore, bringing together an interdisciplinary group of experts from MIT and Singapore, for new research areas at SMART. In addition to our existing research on our three flagship projects, we hope to develop breakthroughs in manufacturing other cell therapy platforms that will enable better medical treatments and outcomes for society,” says Krystyn Van Vliet, co-lead principal investigator at SMART CAMP, professor of materials science and engineering, and associate provost at MIT.

Understanding glaucoma progression for better-targeted treatments

Hosted by SMART CAMP, the first research project, Retinal Analytics via Machine learning aiding Physics (RAMP), brings together an interdisciplinary group of ophthalmologists, data scientists, and optical scientists from SMART, Singapore Eye Research Institute (SERI), Agency for Science, Technology and Research (A*STAR), Duke-NUS Medical School, MIT, and National University of Singapore (NUS). The team will seek to establish first principles-founded and statistically confident models of glaucoma progression in patients. Through retinal biomechanics, the models will enable rapid and reliable forecast of the rate and trajectory of glaucoma progression, leading to better-targeted treatments.

Glaucoma, an eye condition often caused by stress-induced damage over time at the optic nerve head, accounts for 5.1 million of the estimated 38 million blind in the world and 40 percent of blindness in Singapore. Currently, health practitioners face challenges forecasting glaucoma progression and its treatment strategies due to the lack of research and technology that accurately establish the relationship between its properties, such as the elasticity of the retina and optic nerve heads, blood flow, intraocular pressure and, ultimately, damage to the optic nerve head.

The research is co-led by George Barbastathis, principal investigator at SMART CAMP and professor of mechanical engineering at MIT, and Aung Tin, executive director at SERI and professor at the Department of Ophthalmology at NUS. The team includes CAMP principal investigators Nicholas Fang, also a professor of mechanical engineering at MIT; Lisa Tucker-Kellogg, assistant professor with the Cancer and Stem Biology program at Duke-NUS; and Hanry Yu, professor of physiology with the Yong Loo Lin School of Medicine, NUS and CAMP’s co-lead principal investigator.

“We look forward to leveraging the ideas fostered in SMART CAMP to build data analytics and optical imaging capabilities for this pressing medical challenge of glaucoma prediction,” says Barbastathis.

Cell transplantation to treat irreparable spinal cord injury

Engineering Scaffold-Mediated Neural Cell Therapy for Spinal Cord Injury Treatment (ScaNCellS), the second research project, gathers an interdisciplinary group of engineers, cell biologists, and clinician scientists from SMART, Nanyang Technological University (NTU), NUS, IMCB A*STAR, A*STAR, French National Centre for Scientific Research (CNRS), the University of Cambridge, and MIT. The team will seek to design a combined scaffold and neural cell implantation therapy for spinal cord injury treatment that is safe, efficacious, and reproducible, paving the way forward for similar neural cell therapies for other neurological disorders. The project, an intersection of engineering and health, will achieve its goals through an enhanced biological understanding of the regeneration process of nerve tissue and optimized engineering methods to prepare cells and biomaterials for treatment.

Spinal cord injury (SCI), affecting between 250,00 and 500,000 people yearly, is expected to incur higher societal costs as compared to other common conditions such as dementia, multiple sclerosis, and cerebral palsy. SCI can lead to temporary or permanent changes in spinal cord function, including numbness or paralysis. Currently, even with the best possible treatment, the injury generally results in some incurable impairment.

The research is co-led by Chew Sing Yian, principal investigator at SMART CAMP and associate professor of the School of Chemical and Biomedical Engineering and Lee Kong Chian School of Medicine at NTU, and Laurent David, professor at University of Lyon (France) and leader of the Polymers for Life Sciences group at CNRS Polymer Engineering Laboratory. The team includes CAMP principal investigators Ai Ye from Singapore University of Technology and Design; Jongyoon Han and Zhao Xuanhe, both professors at MIT; as well as Shi-Yan Ng and Jonathan Loh from Institute of Molecular and Cell Biology, A*STAR.

Chew says, “Our earlier SMART and NTU scientific collaborations on progenitor cells in the central nervous system are now being extended to cell therapy translation. This helps us address SCI in a new way, and connect to the methods of quality analysis for cells developed in SMART CAMP.”

“Cell therapy, one of the fastest-growing areas of research, will provide patients with access to more options that will prevent and treat illnesses, some of which are currently incurable. Glaucoma and spinal cord injuries affect many. Our research will seek to plug current gaps and deliver valuable impact to cell therapy research and medical treatments for both conditions. With a good foundation to work on, we will be able to pave the way for future exciting research for further breakthroughs that will benefit the health-care industry and society,” says Hanry Yu, co-lead principal investigator at SMART CAMP, professor of physiology with the Yong Loo Lin School of Medicine, NUS, and group leader of the Institute of Bioengineering and Nanotechnology at A*STAR.

The grants for both projects will commence on  Oct. 1, with RAMP expected to run until Sept. 30, 2022, and ScaNCellS expected to run until Sept. 30, 2023.

SMART was. established by the MIT in partnership with the NRF in 2007. SMART is the first entity in the CREATE developed by NRF. SMART serves as an intellectual and innovation hub for research interactions between MIT and Singapore, undertaking cutting-edge research projects in areas of interest to both Singapore and MIT. SMART currently comprises an Innovation Centre and five interdisciplinary research groups (IRGs): Antimicrobial Resistance, CAMP, Disruptive and Sustainable Technologies for Agricultural Precision, Future Urban Mobility, and Low Energy Electronic Systems.

CAMP is a SMART IRG launched in June 2019. It focuses on better ways to produce living cells as medicine, or cellular therapies, to provide more patients access to promising and approved therapies. The investigators at CAMP address two key bottlenecks facing the production of a range of potential cell therapies: critical quality attributes (CQA) and process analytic technologies (PAT). Leveraging deep collaborations within Singapore and MIT in the United States, CAMP invents and demonstrates CQA/PAT capabilities from stem to immune cells. Its work addresses ailments ranging from cancer to tissue degeneration, targeting adherent and suspended cells, with and without genetic engineering.

CAMP is the R&D core of a comprehensive national effort on cell therapy manufacturing in Singapore.

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Anticipating heart failure with machine learning

Every year, roughly one out of eight U.S. deaths is caused at least in part by heart failure. One of acute heart failure’s most common warning signs is excess fluid in the lungs, a condition known as “pulmonary edema.” 

A patient’s exact level of excess fluid often dictates the doctor’s course of action, but making such determinations is difficult and requires clinicians to rely on subtle features in X-rays that sometimes lead to inconsistent diagnoses and treatment plans.

To better handle that kind of nuance, a group led by researchers at MIT’s Computer Science and Artificial Intelligence Lab (CSAIL) has developed a machine learning model that can look at an X-ray to quantify how severe the edema is, on a four-level scale ranging from 0 (healthy) to 3 (very, very bad). The system determined the right level more than half of the time, and correctly diagnosed level 3 cases 90 percent of the time.

Working with Beth Israel Deaconess Medical Center (BIDMC) and Philips, the team plans to integrate the model into BIDMC’s emergency-room workflow this fall.

“This project is meant to augment doctors’ workflow by providing additional information that can be used to inform their diagnoses as well as enable retrospective analyses,” says PhD student Ruizhi Liao, who was the co-lead author of a related paper with fellow PhD student Geeticka Chauhan and MIT professors Polina Golland and Peter Szolovits. 

The team says that better edema diagnosis would help doctors manage not only acute heart issues, but other conditions like sepsis and kidney failure that are strongly associated with edema. 

As part of a separate journal article, Liao and colleagues also took an existing public dataset of X-ray images and developed new annotations of severity labels that were agreed upon by a team of four radiologists. Liao’s hope is that these consensus labels can serve as a universal standard to benchmark future machine learning development.

An important aspect of the system is that it was trained not just on more than 300,000 X-ray images, but also on the corresponding text of reports about the X-rays that were written by radiologists. The team was pleasantly surprised that their system found such success using these reports, most of which didn’t have labels explaining the exact severity level of the edema.

“By learning the association between images and their corresponding reports, the method has the potential for a new way of automatic report generation from the detection of image-driven findings,” says Tanveer Syeda-Mahmood, a researcher not involved in the project who serves as chief scientist for IBM’s Medical Sieve Radiology Grand Challenge. “Of course, further experiments would have to be done for this to be broadly applicable to other findings and their fine-grained descriptors.”

Chauhan’s efforts focused on helping the system make sense of the text of the reports, which could often be as short as a sentence or two. Different radiologists write with varying tones and use a range of terminology, so the researchers had to develop a set of linguistic rules and substitutions to ensure that data could be analyzed consistently across reports. This was in addition to the technical challenge of designing a model that can jointly train the image and text representations in a meaningful manner.

“Our model can turn both images and text into compact numerical abstractions from which an interpretation can be derived,” says Chauhan. “We trained it to minimize the difference between the representations of the X-ray images and the text of the radiology reports, using the reports to improve the image interpretation.”

On top of that, the team’s system was also able to “explain” itself, by showing which parts of the reports and areas of X-ray images correspond to the model prediction. Chauhan is hopeful that future work in this area will provide more detailed lower-level image-text correlations, so that clinicians can build a taxonomy of images, reports, disease labels and relevant correlated regions. 

“These correlations will be valuable for improving search through a large database of X-ray images and reports, to make retrospective analysis even more effective,” Chauhan says.

Chauhan, Golland, Liao and Szolovits co-wrote the paper with MIT Assistant Professor Jacob Andreas, Professor William Wells of Brigham and Women’s Hospital, Xin Wang of Philips, and Seth Berkowitz and Steven Horng of BIDMC. The paper will be presented Oct. 5 (virtually) at the International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI). 

The work was supported in part by the MIT Deshpande Center for Technological Innovation, the MIT Lincoln Lab, the National Institutes of Health, Philips, Takeda, and the Wistron Corporation.

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Antarctic sea ice may not cap carbon emissions as much as previously thought

The Southern Ocean surrounding Antarctica is a region where many of the world’s carbon-rich deep waters can rise back up to the surface. Scientists have thought that the vast swaths of sea ice around Antarctica can act as a lid for upwelling carbon, preventing the gas from breaking through the ocean’s surface and returning to the atmosphere.

However, researchers at MIT have now identified a counteracting effect that suggests Antarctic sea ice may not be as powerful a control on the global carbon cycle as scientists had suspected.

In a study published in the August issue of the journal Global Biogeochemical Cycles, the team has found that indeed, sea ice in the Southern Ocean can act as a physical barrier for upwelling carbon. But it can also act as a shade, blocking sunlight from reaching the surface ocean. Sunlight is essential for phytosynthesis, the process by which phytoplankton and other ocean microbes take up carbon from the atmosphere to grow.

The researchers found that when sea ice blocks sunlight, biological activity — and the amount of carbon that microbes can sequester from the atmosphere — decreases significantly. And surprisingly, this shading effect is almost equal and opposite to that of sea ice’s capping effect. Taken together, both effects essentially cancel each other out. 

“In terms of future climate change, the expected loss of sea ice around Antarctica may therefore not increase the carbon concentration in the atmosphere,” says lead author Mukund Gupta, who carried out the research as a graduate student in MIT’s Department of Earth, Atmospheric and Planetary Sciences (EAPS).

He emphasizes that sea ice does have other effects on the global climate, foremost through its albedo, or ability to reflect solar radiation.

“When the Earth warms up, it loses sea ice and absorbs more of this solar radiation, so in that sense, the loss of sea ice can accelerate climate change,” Gupta says. “What we can say here is, sea ice changes may not have such a strong effect on carbon outgassing around Antarctica through this capping and shading effect.”

Gupta’s coauthors are EAPS Professor Michael “Mick” Follows, and EAPS research scientist Jonathan Lauderdale.

The role of ice

Each winter, wide swaths of the Southern Ocean freeze over, forming vast sheets of sea ice that extend out from Antarctica for millions of square miles. The role of Antarctic sea ice in regulating the climate and the carbon cycle has been much debated, though the prevailing theory has been that sea ice can act as a lid to keep carbon in the ocean from escaping to the atmosphere.

“This theory is mostly thought of in the context of ice ages, when the Earth was much colder and the atmospheric carbon was lower,” Gupta says. “One of the theories explaining this low carbon concentration argues that because it was colder, a thick sea ice cover extended further into the ocean, blocking carbon exchanges with the atmosphere and effectively trapping it in the deep ocean.”

Gupta and his colleagues wondered whether an effect other than capping may also be in play. In general, the researchers have sought to understand how various features and processes in the ocean interact with ocean biology such as phytoplankton. They assumed that there might be less biological activity as a result of sea ice blocking microbes’ vital sunlight — but how strong would this shading effect be?

Equal and opposite

To answer that question, the researchers used the MITgcm, a global circulation model that simulates the many physical, chemical, and biological processes involved in the circulation of the atmosphere and ocean. With MITgcm, they simulated a vertical slice of the ocean spanning 3,000 kilometers wide and about 4,000 meters deep, and with conditions similar to today’s Southern Ocean. They then ran the model multiple times, each time with a different concentration of sea ice.

“At 100 percent concentration, there are no leaks in the ice, and it’s really compacted together, versus very low concentrations representing loose and sparse ice floes moving around,” Gupta explains.

They set each simulation to one of three scenarios: one where only the capping effect is active, and sea ice is only influencing the carbon cycle by preventing carbon from leaking back out to the atmosphere; another where only the shading effect is active, and sea ice is only blocking sunlight from penetrating the ocean; and the last in which both capping and shading effects are in play.

For every simulation, the researchers observed how the conditions they set affected the overall carbon flux, or amount of carbon that escaped from the ocean to the atmosphere.

They found that capping and shading had opposite effects on the carbon cycle, reducing the amount of carbon to the atmosphere in the former case and increasing it in the latter, by equal amounts. In the scenarios where both effects were considered, one canceled the other out almost entirely, across a wide range of sea ice concentrations, leading to no significant change in the carbon flux. Only when sea ice was at its highest concentration did capping have the edge, with a decrease in carbon escaping to the atmosphere.

The results suggest that Antarctic sea ice may effectively trap carbon in the ocean, but only when that ice cover is very expansive and thick. Otherwise, it seems that sea ice’s shading effect on the underlying organisms may counteract its capping effect.

“If one just considered the physics and the pure capping, or carbon barrier idea, that would be an incomplete way of thinking about it,” Gupta says. “This shows that we need to understand more of the biology under sea ice and how it underlies this effect.”

This research was supported in part by the U.S. National Science Foundation.

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