Duke Research Blog

Following the people and events that make up the research community at Duke.

Category: Medicine (Page 1 of 17)

Lemur Research Gets a Gut Check

Baby Coquerel’s sifaka

Clinging to her mom, this baby Coquerel’s sifaka represents the only lemur species at the Duke Lemur Center known to fall prey to cryptosporidium, a microscopic parasite that causes diarrhea that can last for a week or more. The illness wipes out much of the animals’ gut microbiome, researchers report, but fecal transplants can help them recover. Photo by David Haring, Duke Lemur Center.

DURHAM, N.C. — “Stool sample collector” is not a glamorous way to introduce oneself at a party. But in the course of their research, gut microbiologists Erin McKenney and Lydia Greene have spent a lot of time waiting for animals to relieve themselves.

They estimate they have hundreds of vials of the stuff, from a dozen primate species including lemurs, baboons and gorillas, sitting in freezers on the Duke University campus.

The researchers aren’t interested in the poop per se, but in the trillions of bacteria inhabiting the gastrointestinal tract, where the bugs help break down food, produce vitamins and prevent infection.

A few years ago, McKenney and Greene started collecting stool samples at the Duke Lemur Center to see how the microbial makeup of lemurs’ guts varies from birth to weaning, and as their diets change over the seasons. And what happens when they get sick?

Illustration of Cryptosporidium, a widespread intestinal parasite that causes diarrhea in people, pets, livestock and wildlife worldwide. Courtesy of the U.S. Centers for Disease Control.

Illustration of Cryptosporidium, a widespread intestinal parasite that causes diarrhea in people, pets, livestock and wildlife worldwide. Courtesy of the U.S. Centers for Disease Control.

Between 2013 and 2016, ten of the lemurs they were studying contracted cryptosporidium, or “crypto” for short, a waterborne parasite that causes diarrhea in people, pets, livestock and wildlife worldwide.

All of the infected animals were Coquerel’s sifakas — the only lemur species out of roughly 20 at the Duke Lemur Center known to fall prey to the parasite — and most of them were under five years old when they fell ill.

Animals that tested positive were moved into separate holding areas away from other animals and visitors. Keepers wore protective suits, gloves, face masks and booties while working in the animals’ enclosures to prevent infection.

All of the animals eventually recovered. Along the way, six of the affected animals were treated with antibiotics, and three were also fed a slurry of saline and feces from a healthy relative.

McKenney and Greene collected stool samples before, during and after infection for up to two months. They used a technique called 16S ribosomal RNA sequencing to identify the types of bacteria in the samples based on their genes, and compared the results with those of 35 unaffected individuals.

In a healthy gut microbiome, “good” bacteria in the gut compete with “bad” microbes for space and nutrients, and secrete substances that inhibit their growth.

The guts of sick and recovering sifakas are host to a very different assortment of microbes than those of unaffected animals, the researchers found.

Not surprisingly, both crypto infection, and antibiotic treatment, wiped out much of the animals’ gut flora — particularly the bacterial groups Bifidobacterium, Akkermansia, Succinivibrio and Lachnospiraceae.

Even after the infections cleared, most animals took another several weeks to stabilize and return to normal levels of gut biodiversity, with younger animals taking longer to recover.

The only animals that made a full comeback within the study period were those that received a fecal transplant, suggesting that the treatment can help restore gut bacterial diversity and speed recovery.

The patterns of gut recolonization following crypto infection mirrored those seen from birth to weaning, said McKenney, now a postdoctoral researcher at North Carolina State University.

The researchers hope their findings will help control and prevent crypto outbreaks in captive primates. Because lemurs are more closely related to humans than lab mice are, the research could also help scientists understand how the gut microbiome protects humans from similar infections and facilitates recovery.

“Thanks to bioinformatics and advances in sequencing, the microbiome gives us a window into the health of these animals that we’ve never had before,” said Greene, a graduate student in ecology at Duke.

They published their findings June 15, 2017, in the journal Microbial Ecology in Health and Disease.

Duke evolutionary anthropology professors Christine Drea and Anne Yoder were senior authors on this study. This research was supported by the National Science Foundation (1455848) and the Duke Lemur Center Directors Fund.

CITATION:  “Down for the Count: Cryptosporidium Infection Depletes Gut Microbiota in Coquerel’s Sifakas,” Erin McKenney, Lydia Greene, Christine Drea and Anne Yoder. Microbial Ecology in Health and Disease, June 15, 2017. http://dx.doi.org/10.1080/16512235.2017.1335165

Post by Robin Smith, science writer, Office of News & Communications

If the Cancer Doesn’t Kill You, the Drug Prices Might

The medical community is growing alarmed about a creeping malady that can diminish the quality of life for patients in treatment and even shorten their lives.

It’s found everywhere in the United States, but not to the same degree in other developed countries. They’re calling it “Financial Toxicity.”

Yousuf Zafar is an oncologist and health policy researcher.

A cancer diagnosis more than doubles an American’s chance of declaring bankruptcy, Duke medical oncologist  Yousuf Zafar, MD, MHS,  told an audience of nursing faculty and students at a May 10 luncheon lecture sponsored by the Duke Center for Community and Population Health Improvement. And that bankruptcy, in turn, has been shown to decrease survival rates.

In addition to treating cancer patients, Zafar studies access to care and the cost of care at the Duke Cancer Institute, the Sanford School of Public Policy, and the Margolis Center for Health Policy.

Zafar told personal stories of two patients who waved off treatments because of the financial hardship they feared.

Gleevec (Imatinib) is an oral chemotherapy made by Novartis.

One of them had a job with health insurance, but no prescription drug coverage, which put him on the hook for $4,000 in medications to treat his rectal cancer for just a few weeks. Had either the patient or Dr. Zafar brought the topic up, the costs might have been avoided, but they never talked about money, he said.

The other patient passed up another round of treatment for his pancreatic cancer, for fear of the bills his family would be saddled with when he died.

Chemotherapy for cancer would typically cost $100/month in the 1970s, Zafar said. But today that figure can be “ten, or tens, of thousands per month.” (Inflation would make that 1970 dollar about $6, not $600.)

“Pricing in the European Union and the rest of the world is a completely different picture,” he said.  In the US, pricing “simply reflects what the market will bear.”

Another source of the steep climb is the advent of biologic drugs, which are expensive to develop, use and store, but offer more targeted therapy for individual patients. One of the most successful of these is Gleevec (Imatinib) an oral chemotherapy that became 158 percent more expensive from 2007 to 2014, Zafar said.

If you do a Google search for Gleevec, the first thing you find is a Novartis page with the headline “Understand Your Out-Of-Pocket Costs For Gleevec” that includes a link to financial assistance resources.

In the face of outrageous costs and questionable benefits, a treatment team in many cases can help patients find other means of support or alternative treatments to achieve the same end with less financial damage. But they have to have the conversation, Zafar said. He’d like to see Duke’s Cancer Center become the first in the country to be totally transparent about costs, but he acknowledged that it may be a difficult quest.

To help enable those conversations, Zafar developed a mobile app called Pathlight to help patients make more informed decisions and plan better for the financial burden of treatment. For some of the technology used in the project, Zafar has partnered with a software company called Vivor, which has found innovative ways to help patients navigate to financial assistance programs. That part of the project is supported by the NIH’s National Cancer Institute.

Even for people not in treatment, drugs have become more costly. Healthcare premiums rose 182 percent from 1999 to 2013, with workers paying an increasing share of the cost of their own employee health plans.

Is this any way to run a health system?

“I don’t have all the answers – I don’t think anybody does,” Zafar said. “But I think we need to move toward a single-payer system.”

Post by Karl Leif Bates

 

Closing the Funding Gap for Minority Scientists

DURHAM, N.C. — The barriers to minority students in science, technology, engineering and math (STEM) don’t go away once they’ve finished school and landed a job, studies show. But one nationwide initiative aims to level the playing field once they get there.

With support from a 3-year, $500,0000 grant from the National Science Foundation, assistant professors and postdoctoral fellows who come from underrepresented minorities are encouraged to apply by May 5 for a free grant writing workshop to be held June 22-24 in Washington, D.C..

It’s no secret that STEM has a diversity problem. In 2015, African-Americans and Latinos made up 29 percent of the U.S. workforce, but only 11 percent of scientists and engineers.

A study published in the journal Science in 2011 revealed that minority scientists also were less likely to win grants from the National Institutes of Health, the largest source of research funding to universities.

Based on an analysis of 83,000 grant applications from 2000 to 2006, the study authors found that applications from black researchers were 13 percent less likely to succeed than applications from their white peers. Applications from Asian and Hispanic scientists were 5 and 3 percent less likely to be awarded, respectively.

Even when the study authors made sure they were comparing applicants with similar educational backgrounds, training, employers and publication records, the funding gap persisted — particularly for African-Americans.

Competition for federal research dollars is already tough. But white scientists won 29 percent of the time, and black scientists succeeded only 16 percent of the time.

Pennsylvania State University chemistry professor Squire Booker is co-principal investigator of a $500,000 initiative funded by the National Science Foundation to help underrepresented minority scientists write winning research grants.

“That report sent a shock wave through the scientific community,” said Squire Booker, a Howard Hughes Medical Institute investigator and chemistry professor at Pennsylvania State University. Speaking last week in the Nanaline H. Duke building on Duke’s Research Drive, Booker outlined a mentoring initiative that aims to close the gap.

In 2013, Booker and colleagues on the Minority Affairs Committee of the American Society for Biochemistry and Molecular Biology decided to host a workshop to demystify the grant application process and help minority scientists write winning grants.

Grant success is key to making it in academia. Even at universities that don’t make funding a formal requirement for tenure and promotion, research is expensive. Outside funding is often required to keep a lab going, and research productivity — generating data and publishing results — is critical.

To insure underrepresented minorities have every chance to compete for increasingly tight federal research dollars, Booker and colleagues developed the Interactive Mentoring Activities for Grantsmanship Enhancement program, known as IMAGE. Program officers from NIH and NSF offer tips on navigating the funding process, crafting a successful proposal, decoding reviews and revising and resubmitting. The organizers also stage a mock review panel, and participants receive real-time, constructive feedback on potential research proposals.

Participants include researchers in biology, biophysics, biochemistry and molecular biology. More than half of the program’s 130 alumni have been awarded NSF or NIH grants since the workshop series started in 2013.

Booker anticipates this year’s program will include more postdoctoral fellows. “Now we’re trying to expand the program to intervene at an earlier stage,” Booker said.

To apply for the 2017 workshop visit http://www.asbmb.org/grantwriting/.  The application deadline is May 5.

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Post by Robin Smith

Bass Connections and GHANDI – Understanding Disability from a Global Perspective

Duke prides itself on being a research institution that is not only intellectually curious, but also extremely interdisciplinary. Through Duke’s Bass Connections initiative, students and faculty come together in project teams that tackle complex issues using multiple disciplines and approaches. The program held its annual fair last week to showcase its work and to get new students connected with these exciting projects.

How does it work?

Graduate students, undergraduates, and faculty members apply for a research project in any of these five areas: Brain and Society, Information Society & Culture, Global Health, Education & Development, and Energy. Once accepted, group members work on a year-long research project, that often includes a field work component. One project in particular that combines many disciplines and interests to address an issue of global importance GANDHI, a Global Health project that studies disability from multiple cultural perspectives.

What is GANDHI?

GANDHI team members meet with Dr. Rune Simeonsson at UNC to discuss the WHO ICF-CY (International Classification of Functioning – Children and Youth), a document he helped co-write that provides a framework for diagnosing and addressing disability.

The Global Alliance on Disease and Health Innovation (GANDHI) was created in 2016 to support disabled individuals by providing them with the community reintegration tools necessary to live a healthy, comfortable life. Yukhai Lin, a Duke undergrad and GANDHI team member, shared that many hospital systems are not good at helping those the disabled reintegrate themselves in their community, and often forget about their patients after they are released. The research team recognized this flaw, and began a thorough data collection process to understand the reason for this lack of care. In the fall of 2016, team members took a seminar course, “Living with Disability Around the Globe”, in which they were paired with global partners in ten different countries to examine disability from a more specific context. In this interdisciplinary class, team members not only strengthened their knowledge of disability and its implications on global societies, but they were also able to develop strong research skills, for they ultimately synthesized their findings by creating a thorough comparison of disability in each of the countries studied.

The team also attended a conference in New Orleans to network with organizations that were conducting similar research. Lin said she interviewed doctors from The Netherlands, as well as leaders of influential health organizations to holistically understand the issues that come with helping the disabled. The team hopes to present their findings at a forum this spring, and, like many other Bass Connection projects, will continue throughout the 2017-2018 academic year. They encourage all to apply, and hope to broaden the scope of their research by adding countries in Southeast Asia and creating new opportunities for fieldwork. Some eager students have already showed interest in going to China to interview families with disabled members, says Lin.

Other Bass Connections projects at the fair spread across all disciplines, ranging from the development of effective chemotherapy drugs to the study of urban development in cities across the globe. But, what all projects share in common is a strong emphasis on research that is hands-on, collaborative, and relevant to society.

 

Post by Lola Sanchez-Carrion

Using the Statistics of Disorder to Unravel Real-World Chaos

What do election polls, hospital records, and the Syrian conflict have in common? How can a hospital use a patient’s vital signs to calculate their risk of cardiac arrest in real time?

Duke statistical science professor Rebecca Steorts

Duke statistical science professor Rebecca Steorts

Statistician Rebecca Steorts is developing advanced data analysis methods to answer these questions and other pressing real-world problems. Her research has taken her from computer science to biostatistics and hospital care to human rights.

One major focus of Steorts’ research has been estimating death counts in the Syrian civil war. She is working with her research group at Duke and the Human Rights Data Analysis Group (https://hrdag.org/) on combining databases of death records into a single master list of deaths in the conflict, a task known as record linkage.

“The key problem of record linkage is this: you have this duplicated information, how do you remove it?” explained Steorts. For example, journalists from different organizations might independently record the same death in their databases. Those duplicates have to be removed before an accurate death toll can be determined.

At first glance, this might seem like an easy task. But typographic errors, missing information, and inconsistent record-keeping make hunting for duplicates a complex and time consuming problem; a simple algorithm would require days to sort through all the records. So Steorts and her collaborators designed software to sift through the different databases using powerful machine learning techniques. In 2015, she was named one of MIT Technology Review’s 35 Innovators Under 35 for her work on the Syrian conflict. She credits a number of colleagues and students for their contributions to the project, including Anshumali Shrivastava (Rice University), Megan Price (HRDAG), Brenda Betancourt and Abbas Zaid (Duke University), Jeff Miller (Harvard Biostatistics, formerly Duke University), Hanna Wallach (Microsoft Research), and Giacomo Zanella (University of Bocconi and Visitor of Duke University in 2016).

Steorts’ work towards estimating death counts in the Syrian conflict is still ongoing, but human rights isn’t the only field that she plans to study. “I think of my work as very interdisciplinary,” she said. “For me, it’s all about the applications.”

Recently, Steorts, colleague Ben Goldstein, and students Reuben McCreanor and Angie Shen have been applying statistical methods to medical data from the Duke healthcare system. Her ultimate goal is to find techniques that can be used for many different applications and data sets.

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Guest post by Angela Deng, North Carolina School of Science and Math, Class of 2017

Starting Your Own Business in Social Entrepreneurship? Lessons from Four Founders

Interested in starting your own jazz festival? Or creating hydrogen-rich water to boost your circulation and improve muscle recovery?

These are the accomplishments of Cicely Mitchell and Gail Levy, who were among four inspiring leaders at the evening panel discussion in the Fuqua School of Business this past Wednesday. Excited students and faculty gathered in the Kirby Reading room to learn about the leaders’ unique perspectives as founders of non-profit and for-profit solutions to various social impact and sustainability issues.

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Students and faculty gathered for dinner and networking before the panel discussion.

Organized by the Duke Innovation & Entrepreneurship Initiative and the Center for the Advancement of Social Entrepreneurship (CASE), the panel served to enlighten the audience about the challenges the women have faced and the lessons they learned in starting and scaling their social ventures. Panel moderator Erin Worsham, the Executive Director of CASE, opened the discussion with a few statistics.

In the non-profit sector, women make up 75% of the workforce, but in leadership positions, this ratio drops to 45%. As of 2013 in the for-profit sector, only 2.7% of venture capital investments went to fund companies with a female CEO. While black women own 1.5 million businesses in the U.S., they receive only 0.2% of venture funding. Undoubtedly, Worsham concluded, there is a lot of work to do in terms of women getting funded and represented as leaders.

Erin Worsham opened up the panel with statistics about women in the workforce. Worsham is the Executive Director of the award-winning CASE based at Duke University’s Fuqua School of Business

To commence the discussion, Worsham asked the panelists to speak about the gender discrimination they faced while starting their own companies. Gail Levy, founder of H Factor Water, a health-focused company producing hydrogen-infused water in environmentally friendly packaging, answered with a time she was challenged to a drinking match in order to close a deal. “The lesson I learned is to not go and drink your way into making a deal,” Levy joked. “But more importantly, you need to have grit and tenacity. Let our presence be known, because eventually we will be heard.”

Gail

Gail Levy was the founder of the White House Millennium Green Committee under the Clinton Administration in 1999. She is passionate about advocating for women worldwide and is also the founder of H Factor Water.

Founder of The Art of Cool, a Durham nonprofit promoting music education to Durham-area youth, Cecily Mitchell remarked that she would be charged significantly more money than a male counterpart to work with the same artist.

Cicely Mitchell is co-founder of The Art of Cool, a Durham nonprofit promoting music education to Durham-area youth

Cicely Mitchell is co-founder of The Art of Cool, a Durham nonprofit promoting music education to Durham-area youth

Rebecca Ballard, lawyer and founder of Maven Women, a sustainability-focused fashion company dedicated to making professional wear for women, noted that “we live in a visual world, but we need to start looking at a person’s character rather than solely focusing on how they look.” Based on her experience with her medical real estate development company ACCESS Medical Development, angel investor Stephanie Wilson expanded on the comment, adding that the best thing to do about the prejudice against women is to know that it’s there and fight for it.

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Rebecca Ballard told the audience, “The most challenging thing about being a working woman is that appearance is considered ‘relevant.’” She started her career as a public interest lawyer and was previously the Executive Director of Social Impact 360.

I asked the founders to share their experiences in building a successful customer base. Wilson noted that to institute her company, she “determined who was the top real estate agent in our area and sought them out. I discussed my idea with them and asked for their advice on segueing into the market.” She suggested sending handwritten thank you notes to build relationships with your customers.

Stephanie Wilson founded ACCESS Medical Development and is also the co-founder of MillennialsMovingMillions.org.

Stephanie Wilson founded ACCESS Medical Development and is also the co-founder of MillennialsMovingMillions.org.

Mitchell added that The Art of Cool held the first few concerts for relatives and friends, and later partnered up with other small entrepreneurs. “Make sure what you do connects with people enough that they want to go and tell other people about what you’re doing,” she advised.

Cecily Mitchell talked about her experience with The Art of Cool. She handles the booking, contracts, networking, pitching for sponsorships and assisting in writing grants for the company.

Maven Woman founder Rebecca Ballard commented on the importance getting support from women in other sustainable industries, since “you are all driven by the same mission in the social entrepreneurship space.”

Rebecca

Rebecca Ballard is the founder of Maven Women, a sustainability-focused fashion company dedicated on making professional wear for women.

Worsham’s final question for the panel asked for any last pieces of advice. Ballard concluded the conversation with a reason why she started her company: “Social entrepreneurship exists because the status quo is not okay. There are externalities happening and people being treated badly; the status quo doesn’t have to be the way it is.”

From left to right:

Posing with the panelists! From left to right: Anika Radiya-Dixit (author), Gail Levy, Cecily Mitchell, Rebecca Ballard, and Stephanie Wilson.

By Anika Radiya-Dixit

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