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HIV Can Be Treated, But Stigma Kills

Three decades ago, receiving an HIV diagnosis was comparable to being handed a death sentence. But today, this is no longer the case.

Advances in HIV research have led to treatments that can make the virus undetectable and untransmittable in less than six months, a fact that goes overlooked by many. Treatments today can make HIV entirely manageable for individuals.

However, thousands of Americans are still dying of HIV-related causes each year, regardless of the fact that HIV treatments are accessible and effective. So where is the disconnect coming from?

On the 30th anniversary of World AIDS Day, The Center for Sexual and Gender Diversity at Duke University hosted a series of events surrounding around this year’s international theme: “Know Your Status.”

One of these events was a panel discussion featuring three prominent HIV/AIDS treatment advocates on campus, Dr. Mehri McKellar, Dr. Carolyn McAllaster, and Dr. Kent Weinhold, who answered questions regarding local policy and current research at Duke.

From left to right: Kent Weinhold, Carolyn McAllaster, Mehri McKellar and moderator Jesse Mangold in Duke’s Center for Sexual and Gender Diversity

The reason HIV continues to spread and kill, Dr. McKellar explained, is less about accessibility, and more about stigma. Research has shown that stigma shame leads to poor health outcomes in HIV patients, and unfortunately, stigma shame is a huge problem in communities across the US.

Especially in the South, she said, there is very little funding for initiatives to reduce stigma surrounding HIV/AIDS, and people are suffering as a result.

In 2016, the CDC reported that the South was responsible for 52 percent of all new HIV diagnoses and 47 percent of all HIV-related deaths in the US.

If people living with HIV don’t feel supported by their community and comfortable in their environment, it makes it very difficult for them to obtain proper treatment. Dr. McKellar’s patients have told her that they don’t feel comfortable getting their medications locally because they know the local pharmacist, and they’re ashamed to be picking up HIV medications from a familiar face.

 

HIV/AIDS Diagnoses and Deaths in the US 1981-2007 (photo from the CDC)

In North Carolina, the law previously required HIV-positive individuals to disclose their status and use a condom with sexual partners, even if they had received treatment and could no longer transmit the virus. Violating this law resulted in prosecution and a prison sentence for many individuals, which only enforced the negative stigma surrounding HIV. Earlier this year, Dr. McAllaster helped efforts to create and pass a new version of the law, which will make life a lot easier for people living with HIV in North Carolina.

So what is Duke doing to help the cause? Well, In 2005, Duke opened the Center for AIDS Research (also known as CFAR), which is now directed by Dr. Kent Weinhold. In the last decade, they have focused their efforts mainly on improving the efficacy of the HIV vaccine. The search for a successful vaccine has been long and frustrating for CFAR and the Duke Human Vaccine Institute, but Dr. Weinhold is optimistic that they will be able to reach the realistic goal of 60 percent effectiveness in the future, although he shied away from predicting any sort of timeline for this outcome.

Pre-exposure prophylaxis or PrEP (photo from NIAID)

Duke also opened a PrEP Clinic in 2016 to provide preventative treatment for individuals who might be at risk of getting HIV. PrEP stands for pre-exposure prophylaxis, and it is a medication that is taken before exposure to HIV to prevent transmission of the virus. Put into widespread use, this treatment is another way to reduce negative HIV stigma.

The problem persists, however, that the people who most need PrEP aren’t getting it. The group that has the highest incidence of HIV is males who are young, black and gay. But the group most commonly receiving PrEP is older, white, gay men. Primary care doctors, especially in the South, often won’t prescribe PrEP either. Not because they can’t, but because they don’t support it, or don’t know enough about it.

And herein lies the problem, the panelists said: Discrimination and bias are often the results of inadequate education. The more educated people are about the truth of living with HIV, and the effectiveness of current treatments, the more empathetic they will be towards HIV-positive individuals.

There’s no reason for the toxic shame that exists nationwide, and attitudes need to change. It’s important for us to realize that in today’s world, HIV can be treated, but stigma kills.

Post by Anne Littlewood

Medicine, Research and HIV

Duke senior Jesse Mangold has had an interest in the intersection of medicine and research since high school. While he took electives in a program called “Science, Medicine, and Research,” it wasn’t until the summer after his first year at Duke that he got to participate in research.

As a member of the inaugural class of Huang fellows, Mangold worked in the lab of Duke assistant professor Christina Meade on the compounding effect of HIV and marijuana use on cognitive abilities like memory and learning.

The following summer, Mangold traveled to Honduras with a group of students to help with collecting data and also meeting the overwhelming need for eye care. Mangold and the other students traveled to schools, administered visual exams, and provided free glasses to the children who needed them. Additionally, the students contributed to a growing research project, and for their part, put together an award-winning poster.

Mangold’s (top right) work in Honduras helped provide countless children with the eye care they so sorely needed.

Returning to school as a junior, Mangold wanted to focus on his greatest research interest: the molecular mechanisms of human immunodeficiency virus (HIV). Mangold found a home in the Permar lab, which investigates mechanisms of mother-to-child transmission of viruses including HIV, Zika, and Cytomegalovirus (CMV).

From co-authoring a book chapter to learning laboratory techniques, he was given “the opportunity to fail, but that was important, because I would learn and come back the next week and fail a little bit less,” Mangold said.

In the absence of any treatment, mothers who are HIV positive transmit the virus to their infants only 30 to 40 percent of the time, suggesting a component of the maternal immune system that provides at least partial protection against transmission.

The immune system functions through the activity of antibodies, or proteins that bind to specific receptors on a microbe and neutralize the threat they pose. The key to an effective HIV vaccine is identifying the most common receptors on the envelope of the virus and engineering a vaccine that can interact with any one of these receptors.

This human T cell (blue) is under attack by HIV (yellow), the virus that causes AIDS. Credit: Seth Pincus, Elizabeth Fischer and Austin Athman, National Institute of Allergy and Infectious Diseases, National Institutes of Health

This human T cell (blue) is under attack by HIV (yellow), the virus that causes AIDS. Credit: Seth Pincus, Elizabeth Fischer and Austin Athman, National Institute of Allergy and Infectious Diseases, National Institutes of Health

Mangold is working with Duke postdoctoral associate Ashley Nelson, Ph.D., to understand the immune response conferred on the infants of HIV positive mothers. To do this, they are using a rhesus macaque model. In order to most closely resemble the disease path as it would progress in humans, they are using a virus called SHIV, which is engineered to have the internal structure of simian immunodeficiency virus (SIV) and the viral envelope of HIV; SHIV can thus serve to naturally infect the macaques but provide insight into antibody response that can be generalized to humans.

The study involves infecting 12 female monkeys with the virus, waiting 12 weeks for the infection to proceed, and treating the monkeys with antiretroviral therapy (ART), which is currently the most effective treatment for HIV. Following the treatment, the level of virus in the blood, or viral load, will drop to undetectable levels. After an additional 12 weeks of treatment and three doses of either a candidate HIV vaccine or a placebo, treatment will be stopped. This design is meant to mirror the gold-standard of treatment for women who are HIV-positive and pregnant.

At this point, because the treatment and vaccine are imperfect, some virus will have survived and will “rebound,” or replicate fast and repopulate the blood. The key to this research is to sequence the virus at this stage, to identify the characteristics of the surviving virus that withstood the best available treatment. This surviving virus is also what is passed from mothers on antiretroviral therapy to their infants, so understanding its properties is vital for preventing mother-to-child transmission.

As a Huang fellow, Mangold had the opportunity to present his research on the compounding effect of HIV and marijuana on cognitive function.

Mangold’s role is looking into the difference in viral diversity before treatment commences and after rebound. This research will prove fundamental in engineering better and more effective treatments.

In addition to working with HIV, Mangold will be working on a project looking into a virus that doesn’t receive the same level of attention as HIV: Cytomegalovirus. CMV is the leading congenital cause of hearing loss, and mother-to-child transmission plays an important role in the transmission of this devastating virus.

Mangold and his mentor, pediatric resident Tiziana Coppola, M.D., are authoring a paper that reviews existing literature on CMV to look for a link between the prevalence of CMV in women of child-bearing age and whether this prevalence is predictive of the number of children suffer CMV-related hearing loss. With this study, Mangold and Coppola are hoping to identify if there is a component of the maternal immune system that confers some immunity to the child, which can then be targeted for vaccine development.

After graduation, Mangold will continue his research in the Permar lab during a gap year while applying to MD/PhD programs. He hopes to continue studying at the intersection of medicine and research in the HIV vaccine field.

Post by undergraduate blogger Sarah Haurin

Post by undergraduate blogger Sarah Haurin

 

Outsmarting HIV With Vaccine Antigens Made to Order

AIDS vaccine researchers may be one step closer to outwitting HIV, thanks to designer antibodies and antigens made to order at Duke.

HIV was identified as the cause of AIDS in 1983. Despite decades of progress in understanding the virus, an effective vaccine remains elusive.

The lack of success is partly due to HIV’s uncanny ability to evade the immune system.

IMG_0674

Duke graduate student Mark Hallen and his advisor, Duke computer science and chemistry professor Bruce Donald. Hallen was awarded a 2015 Liebmann Fellowship for graduate studies.

Now, a team of researchers including Duke computer scientist Bruce Donald and graduate student Mark Hallen have published a 3-D close-up of a designer protein that, if injected into patients, could help the immune system make better antibodies against the virus — a step forward in the 30-year HIV vaccine race.

Led by structural biologist Peter Kwong at the Vaccine Research Center in Bethesda, Maryland, the team’s findings appeared online June 22 in the journal Nature Structural & Molecular Biology.

More than 35 million people worldwide are living with HIV, and about two million more people are infected each year.

Antiretroviral drugs can prevent the virus from reproducing in the body once someone is infected, but only a vaccine can stop it from spreading from one person to the next.

Vaccines work by triggering the immune system to make specialized proteins called antibodies, which prime the body to fight foreign substances. But in the case of HIV, not all antibodies work equally well.

One reason is that HIV is always mutating in the body.

3D print of HIV. Thousands of times smaller than the width of a human hair, the virus is covered with proteins (purple) that enable it to enter and infect human cells. Photo by Daniel Mietchen via Wikimedia Commons.

3D print of HIV. In real life the virus is thousands of times smaller than the width of a human hair. HIV is covered with proteins (purple) that enable it to enter and infect human cells. Photo by Daniel Mietchen via Wikimedia Commons.

HIV incorporates its genetic material into the DNA of its host, hijacking the cell’s replication machinery and forcing it to make more copies of the virus. Each round of replication generates small genetic “mistakes,” resulting in slightly different copies that the host’s antibodies may no longer recognize.

Even before the body makes an antibody that works against one strain, the virus mutates again and makes a new one.

“It’s a race against a moving target,” said Hallen, who was also an undergraduate at Duke majoring in chemistry and mathematics.

In the early 1990s, researchers discovered that a tiny fraction of people infected with HIV are able to produce antibodies that protect against many different strains at once.

These “broadly neutralizing antibodies” fasten to the virus’s surface like a key in a lock and prevent it from invading other cells.

But HIV can evade detection by these powerful antibodies, as the part of its outer coat that is vulnerable to their attack is constantly changing shape.

To overcome this problem, first the researchers needed a close-up look at the region of interest — a spike-shaped virus protein known as Env — in its most vulnerable state.

A 3-D closeup of a key virus protein frozen in a shape the researchers say could serve as a template for a vaccine. Image courtesy of Bruce Donald.

A 3-D closeup of a key virus protein frozen in a shape the researchers say could serve as a template for a vaccine. Image courtesy of Bruce Donald.

With this 3-D blueprint in hand, Hallen and former Duke PhD Ivelin Georgiev developed a scoring system and rated dozens of antibodies according to how well they bound to it. They confirmed that the specific conformation of the Env protein they identified was visible to effective antibodies but not ineffective ones.

The team then identified amino acid sequence changes that would freeze the protein in the desired shape.

Once locked in place, the researchers say, the protein could be injected into patients and used to coax their immune systems into preferentially churning out only the most effective antibodies.

“The idea is to ‘tie’ the protein so that it can’t transition to some other conformation and elicit ineffective antibodies as soon as the effective antibodies bind,” Donald said.

Support for this research included grants from the US National Institutes of Health, the US National Institutes of General Medical Sciences, the US National Institute of Heart, Lung and Blood, the US National Science Foundation and the Bill and Melinda Gates Foundation.

CITATION: “Crystal Structure, Conformational Fixation and Entry-Related Interactions of Mature Ligand-Free HIV-1 Env’,” Kwon, Y. et al. Nature Structural & Molecular Biology, June 22, 2015. DOI: 10.1038/nsmb.3051.

RobinSmith_hed100

 

Robin Smith joined the Office of News and Communications in 2014 after more than ten years as a researcher and writing teacher at Duke. She covers the life and physical sciences across campus.

 

 

Vulci 3000: Technology in Archaeology

This is Anna’s second post from a dig site in Italy this summer. Read the first one here.

Duke PhD Candidate Antonio LoPiano on Site

Once home to Etruscan and Roman cities, the ruins found at Vulci date to earlier than the 8th century B.C.E.

As archaeologists dig up the remains of these ancient civilizations, they are better able to understand how humans from the past lived their daily lives. The problem is, they can only excavate each site once.

No matter how careful the diggers are, artifacts and pieces of history can be destroyed in the process. Furthermore, excavations take a large amount of time, money and strenuous labor to complete. As a result, it’s important to carefully choose the location.

Map of the Vulci Landscape Created Using GIS Technology

In response to these challenges Dr. Maurizio Forte decided to supplement the excavation of ancient Vulci sites by using innovative non-invasive technologies. 

Considering that it once housed entire cities, Vulci is an extremely large site. To optimize excavation time, money, and resources, Dr. Forte used technologies to predict the most important urban areas of the site. Forte and his team also used remote sensing which allowed them to interpret the site prior to digging. 

Georadar Imaging
Duke Post Doc Nevio Danelon Gathering Data for Photogrammetry

Having decided where on the site to look, the team was then able to digitally recreate both the landscape as well as the excavation trench in 3D. This allowed them to preserve the site in its entirety and uncover the history that lay below. Maps of the landscape are created using Web-GIS (Geographic Information Systems). These are then combined with 3D models created using photogrammetry to develop a realistic model of the site.

Forte decided to make the excavation entirely paperless. All “paperwork”  on site is done on tablets. There is also an onsite lab that analyzes all of the archaeological discoveries and archives them into a digital inventory.

This unique combination of archaeology and technology allows Forte and his team to study, interpret and analyze the ancient Etruscan and Roman cities beneath the ground of the site in a way that has never been done before. He is able to create exact models of historic artifacts, chapels and even entire cities that could otherwise be lost for good.

3D Model Created Using Photogrammetry

Forte also thinks it is important to share what is uncovered with the public. One way he is doing this is through integrating the excavation with virtual reality applications.

I’m actually on site with Forte and the team now. One of my responsibilities is to take photos with the Insta360x which is compatible with the OculusGo, allowing people to experience what it’s like to be in the trench with virtual reality. The end goal is to create interactive applications that could be used by museums or individuals. 

Ultimately, this revolutionary approach to archaeology brings to light new perspectives on historical sites and utilizes innovative technology to better understand discoveries made in excavations.

By: Anna Gotskind ’22

We Can’t Regrow Limbs Like Deadpool, But This Creature Can

Try as we might, humans can’t regrow limbs. But losing your left leg isn’t such a problem for axolotls.

Image result for axolotl

Last Wednesday, Dr. Jessica Whited gave a fascinating talk about the importance of studying these strange little salamanders. Axolotls are capable of regenerating lost limbs so well that once a limb has fully grown back, you can’t tell the difference. No scars, no deformities. This genetic phenomenon serves as a powerful model for uncovering what mechanisms might be required for stimulating regeneration in humans.

The limb regeneration process goes through a few stages. Within hours after amputation, a wound epidermis forms around the injury. Next, a blastema grows – a big clump of cells that will be the basis for future growth. After that, a new limb just kind of sprouts out as you might imagine.

Image result for axolotl limb regeneration

So what gives the axolotl this seemingly magical ability? In attempt to answer that question, Whited’s lab looked at how the process starts – specifically at the creation of the blastema, something mammals do not form post-injury. They found that a single amputation causes an activation of progenitor cells throughout the axolotl’s body. Cells in the heart, liver, spinal cord, and contralateral limb all reenter circulation. Essentially an activation signal is sent throughout the whole body, indicating a systemic response to the injury rather than a local one.

Another question Whited sought to answer was if the same limb could regenerate multiple times. She had her student Donald Bryant carry out an experiment on a group of axolotls. Bryant would repeatedly amputate the same limb, letting it fully regrow for ten weeks between amputations. The results of the experiment show that after five amputations only 60 percent of the limb would regenerate. This percentage decreased with the number of amputations. So while axolotls may seem like they have super powers, they aren’t exactly invincible. They decline in their regenerative capabilities after repeated amputation.

Protein EYA2 PDB 3GEB.png

A key finding in this experiment was that repeated amputation led to a decrease in the EYA2 gene (Eyes Absent 2). This particular gene was deemed necessary for the blastema cells to progress through different growth checkpoints. It is required during the cell cycle “to execute decisions about whether the cells will continue to proliferate or not.” So while we don’t exactly know why, we do know that EYA2 plays an important role in the axolotl’s regenerative powers.

Although Whited and her team were able to uncover some important findings, several questions still linger. How is the activation of EYA2 induced following amputation? Why is repeated amputation linked to less EYA2 genes? If cells are poised to anticipate injury / DNA damage, why is it that repeated amputation leads to less regeneration?

Image result for deadpool baby hand

Humans and other mammals are not quite as lucky as the axolotl. Amputation is a relevant and serious issue, yet no biological solution has been devised. Thankfully, the research conducted around axolotl regenerative properties could provide us with knowledge on natural cellular reprogramming. Maybe one day we’ll be able to regrow limbs just like Deadpool.

Will Sheehan
Post by Will Sheehan

Gene-Editing Human Embryos: What, How, Why?

Every seat full. Students perched on the aisle stairs and lining the back walls.

What topic could possibly pull so many away from their final exams? Not “How to Stop Procrastinating” nor “How to Pass Life After Failing Your Exams” but rather “Gene-Editing Human Embryos: Unpacking the Current Controversy” on the Duke campus.

Since Chinese researcher He Jiankui announced at the Second International Summit on Human Genome Editing in Hong Kong that he made the world’s first genetically engineered babies, a debate on the ethical implications has raged on social media.

On December 6, the University Program in Genetics and Genomics and the Molecular Genetics and Microbiology department co-hosted a panel responding to He’s claims. Charles A. Gersbach from the Biomedical Engineering department lead the discussion of what exactly happened and then joined the panel which also contained Misha Angrist, a senior fellow in the Science & Society initiative;  Heidi Cope, a genetic counselor; Giny Fouda, an assistant professor in pediatrics; and Vandana Shashi, a genetic counselor.

Dr. He Jiankui announced he had used CRISPR to edit genes in twin embryos that were then born at full term.

But what exactly has He potentially done to these twin girls? Can they fly? Breathe underwater? Photosynthesize? Not exactly. He said he deleted a gene called CCR5 to increase their HIV resistance. Two percent of Northern Europeans naturally have a mutation that removes the CCR5 gene from their DNA and as a result do not display any traits other than increased HIV resistance.

Many researchers have explored blocking CCR5 activity as a potential HIV treatment. Using CRISPR-Cas9, a genetic engineering technology that can cut and paste specific sequences in the DNA, He targeted CCR5 during in vitro fertilization. According to his tests, he successfully removed both copies of the CCR5 gene in one of the girls. However, in the other girl, the CCR5 remained normal on one chromosome and on the other, CRISPR had deleted more than intended.  The effects of that additional deletion are unknown. 
Both the girls are mosaics, meaning the genetic change occurred in some of their cells and not in others, leading to still more uncertainties.

Researchers have conducted genetic engineering experiments on both somatic cells and human embryo cells that were never brought to term. (Somatic cells constitute all parts of the body other than the eggs and sperm.) But because He altered the twin girls as embryos and then they grew to full term, their children could inherit these changes. This alters their family line, not just a single individual, increasing the ethical implications.

According to Shashi, He’s experiment becomes difficult to justify. Additionally, embryos have not consented to these changes in their genetics, unlike a patient undergoing genetic therapy.

Many doctors, scientists, and journalists have also questioned He’s lack of transparency because he hid this work until his grand announcement, which caused China to arrest him. In addition, as Cope explained, “it is not typically the PI who does the informed consent process” as He did with these parents.

While He defends his work by saying that the girls’ father carries HIV and wished to increase the girls’ safety, the twins were not actually at great risk for HIV. Their father’s medical history does not increase their chances of contracting the virus, and the overall risk for HIV in China is low. As Fouda emphasized in the panel, “there was no justification for this experiment.” While He discussed the potential for genetic engineering to help society, for these two individuals, no medical need existed, and that increases the ethical dilemma.

A final concern of researchers is the current inability to ensure technical competency and accuracy. As seen by the additional deletion in one of the girls,  CRISPR-Cas9 still makes errors. Thus using it to alter not only a human being but all of that individual’s progeny would demand a much higher standard, something close to a life-or-death scenario.

But, the panelists also noted, if it hadn’t been He, it would have been somebody else. Perhaps somebody else may have done it more ethically with more transparency and a more traditional consent process, Angrist said.

While He’s claims have yet to be proven, the fact that they could reasonably be true has many concerned. The World Health Organization has announced that they will begin greater oversight of genetic engineering of the human germline.

On campus over the last weeks, I’ve heard mixed reviews on He’s work with some joking about future superhero babies while others have reacted with fear. The technology does live among us; however, the world is working on writing the guidebook and unrolling the yellow tape.

Post by Lydia Goff

Meet New Blogger Anne Littlewood – Working on Biology and Puppies

My name is Anne Littlewood and I am a sophomore here at Duke. I grew up in San Francisco, spent a brief moment living on the island of Kauai, and finished high school in Pebble Beach, California. I am studying the intersection of biology and psychology here at Duke, in an effort to understand how biological mechanisms inform our interactions with the environment.

Snuggles in Puppy Kindergarten!

Outside the classroom, I can be found frequenting Duke’s beloved Puppy Kindergarten, where I work as a volunteer. Recently, I’ve become an Associate Editor for Duke’s literary magazine, The Archive. I love writing creatively, and it’s been so great to find a community of my literature- loving peers. I’m also participating in a Bass Connections project this year, and working on a team to evaluate the outcomes of different conservation interventions through the synthesis of an evidence gap map for World Wildlife fund.

Me and Cricket on Carmel Beach

Most of all I love to spend time outdoors, whether it’s exploring the mountains of North Carolina on a backpacking trip, lying in my hammock at Eno Quarry, or walking through the gardens each day on my way to class. I’m a huge animal lover, and I’m way too obsessed with my dog, a 12-pound cavalier King Charles spaniel named Cricket.

I’ve always been into science, but I think I really fell in love with Biology my freshman year of high school, when my all time favorite teacher, Mr. Cinti helped me extract my DNA one afternoon, just for fun. Writing is my passion, and I’m excited to explore my skills in a variety of genres this year. This blog is my first ever attempt at journalism/ science writing, and I’m excited to give it a try!

What Happens When Data Scientists Crunch Through Three Centuries of Robinson Crusoe?

Reading 1,400-plus editions of “Robinson Crusoe” in one summer is impossible. So one team of students tried to train computers to do it for them.

Reading 1,400-plus editions of “Robinson Crusoe” in one summer is impossible. So one team of students tried to train computers to do it for them.

Since Daniel Defoe’s shipwreck tale “Robinson Crusoe” was first published nearly 300 years ago, thousands of editions and spinoff versions have been published, in hundreds of languages.

A research team led by Grant Glass, a Ph.D. student in English and comparative literature at the University of North Carolina at Chapel Hill, wanted to know how the story changed as it went through various editions, imitations and translations, and to see which parts stood the test of time.

Reading through them all at a pace of one a day would take years. Instead, the researchers are training computers to do it for them.

This summer, Glass’ team in the Data+ summer research program used computer algorithms and machine learning techniques to sift through 1,482 full-text versions of Robinson Crusoe, compiled from online archives.

“A lot of times we think of a book as set in stone,” Glass said. “But a project like this shows you it’s messy. There’s a lot of variance to it.”

“When you pick up a book it’s important to know what copy it is, because that can affect the way you think about the story,” Glass said.

Just getting the texts into a form that a computer could process proved half the battle, said undergraduate team member Orgil Batzaya, a Duke double major in math and computer science.

The books were already scanned and posted online, so the students used software to download the scans from the internet, via a process called “scraping.” But processing the scanned pages of old printed books, some of which had smudges, specks or worn type, and converting them to a machine-readable format proved trickier than they thought.

The software struggled to decode the strange spellings (“deliver’d,” “wish’d,” “perswasions,” “shore” versus “shoar”), different typefaces between editions, and other quirks.

Special characters unique to 18th century fonts, such as the curious f-shaped version of the letter “s,” make even humans read “diftance” and “poffible” with a mental lisp.

Their first attempts came up with gobbledygook. “The resulting optical character recognition was completely unusable,” said team member and Duke senior Gabriel Guedes.

At a Data+ poster session in August, Guedes, Batzaya and history and computer science double major Lucian Li presented their initial results: a collection of colorful scatter plots, maps, flowcharts and line graphs.

Guedes pointed to clusters of dots on a network graph. “Here, the red editions are American, the blue editions are from the U.K.,” Guedes said. “The network graph recognizes the similarity between all these editions and clumps them together.”

Once they turned the scanned pages into machine-readable texts, the team fed them into a machine learning algorithm that measures the similarity between documents.

The algorithm takes in chunks of texts — sentences, paragraphs, even entire novels — and converts them to high-dimensional vectors.

Creating this numeric representation of each book, Guedes said, made it possible to perform mathematical operations on them. They added up the vectors for each book to find their sum, calculated the mean, and looked to see which edition was closest to the “average” edition. It turned out to be a version of Robinson Crusoe published in Glasgow in 1875.

They also analyzed the importance of specific plot points in determining a given edition’s closeness to the “average” edition: what about the moment when Crusoe spots a footprint in the sand and realizes that he’s not alone? Or the time when Crusoe and Friday, after leaving the island, battle hungry wolves in the Pyrenees?

The team’s results might be jarring to those unaccustomed to seeing 300 years of publishing reduced to a bar chart. But by using computers to compare thousands of books at a time, “digital humanities” scholars say it’s possible to trace large-scale patterns and trends that humans poring over individual books can’t.

“This is really something only a computer can do,” Guedes said, pointing to a time-lapse map showing how the Crusoe story spread across the globe, built from data on the place and date of publication for 15,000 editions.

“It’s a form of ‘distant reading’,” Guedes said. “You use this massive amount of information to help draw conclusions about publication history, the movement of ideas, and knowledge in general across time.”

This project was organized in collaboration with Charlotte Sussman (English) and Astrid Giugni (English, ISS). Check out the team’s results at https://orgilbatzaya.github.io/pirating-texts-site/

Data+ is sponsored by Bass Connections, the Information Initiative at Duke, the Social Science Research Institute, the departments of Mathematics and Statistical Science and MEDx. This project team was also supported by the Duke Office of Information Technology.

Other Duke sponsors include DTECH, Duke Health, Sanford School of Public Policy, Nicholas School of the Environment, Development and Alumni Affairs, Energy Initiative, Franklin Humanities Institute, Duke Forge, Duke Clinical Research, Office for Information Technology and the Office of the Provost, as well as the departments of Electrical & Computer Engineering, Computer Science, Biomedical Engineering, Biostatistics & Bioinformatics and Biology.

Government funding comes from the National Science Foundation.

Outside funding comes from Lenovo, Power for All and SAS.

Community partnerships, data and interesting problems come from the Durham Police and Sheriff’s Department, Glenn Elementary PTA, and the City of Durham.

Videos by Paschalia Nsato and Julian Santos; writing by Robin Smith

Oral Histories of the Gulag

Gulag Voices: Oral Histories of Soviet Detention and Exile (2011), edited by Jehanne M. Gheith and Katherine R. Jolluck, brings interviews with Gulag survivors to English-speaking audiences. In an interview with Gheith, she reflected on how she began her research on the Soviet forced labor camps called Gulags, ethical complications and different kinds of research opportunities for students.

Dr. Jehanne M. Gheith, Associate Professor of Russian Culture at Duke University and Licensed Clinical Social Worker for Duke Hospice

In the early 1990s, Gheith taught a Gulag memoir to Duke students and realized that while students are aware of the Holocaust, their knowledge on Gulags is limited. After the dissolution of the Soviet Union in the 1990’s, it was possible for Gheith to interview Gulag survivors. She and her co-editor, Katherine Jolluck, connected ten years later when Jolluck was a professor at Stanford. Jolluck had published Exile and Identity: Polish Women in the Soviet Union During World War II, a book about Polish women in the Gulag, the two embarked on a collaborative partnership. Taking the interviews  Gheith had conducted, she and  Jolluck added archival sections and reviewed the interviews.

Memoirs and scholarly works differ from collections of interviews. Gheith felt it was important to conduct a project where she and others could hear the stories of survivors. An influential source that she consulted was the The Gulag Archipelago 1981-1956 (1973) by Nobel Literature Prize winner Aleksandr Solzhenitsyn. The Gulag Archipelago covers three volumes of Solzhenitsyn’s personal experience in the Russian Gulags and his critiques on the Stalin regime.

To find interview subjects for the oral project, Gheith contacted the Russian civil rights organization Memorial. She also interviewed people outside of Memorial using what she described as a “snowball sample.” To piece together the fragmented memories of survivors, Gheith listened and transcribed the stories in the order they were remembered with connecting passages of text. Though time can lead to the misrepresentation of facts, Gheith said, “the facts may be wrong, but you can get to emotional truths.” People may incorrectly recall small details due to numerous factors – nevertheless, through Memorial,  Gheith and Jolluck were able to verify key records of camp survivors, showing the years they were in the camps and the kinds of work they did there.

There were ethical complications Gheith had to surmount – participants could be reluctant to speak about their experiences and expressed surprise that audiences were interested in their memories. Some interviewees were fearful of the Gulag re-occurring and needed to be connected to support resources upon being asked about their encounters.

Gheith also needed to be vigilant about the context and history surrounding Gulags. Because Gulag survivors may have been forced to sign false confessions in the labor camps, Gheith had approval from the Institutional Review Board  to secure verbal agreements on tape in lieu of consent forms.

For students conducting interviews, Gheith suggested reading an oral history, communicating with experts and beginning with a smaller project. Additionally, she had two key points: 1) it is crucial to gain approval from the Institutional Review Board to work with human subjects and 2) if conducting research in a foreign language, the choice between a translator or transcriber should be carefully made, as a translator may shift the relationship dynamic.

In the future, Gheith will be connecting her clinical work to Russian literature and culture. She believes that for students interested in medicine, the arts and humanities have a significant connection to scientific research. Storytelling is also a key part of law and policy, and as students begin to conduct studies in these fields, they are likely to find that the ability to weave a narrative is an indispensable skill. Gheith said she would be happy to talk about the connections between story and medicine with any interested students.

By Ameya Sanyal

Smoking Weed: the Good, Bad and Ugly

DURHAM, N.C. — Research suggests that the earlier someone is exposed to weed, the worse it is for them.

Very early on in our life, we develop basic motor and sensory functions. In adolescence, our teenage years, we start developing more complex functions — cognitive, social and emotional functions. These developments differ based on one’s experience growing up — their family, their school, their relationships — and are fundamental to our growth as healthy human beings.

This process has shown to be impaired when marijuana is introduced, according to Dr. Diana Dow-Edwards of SUNY Downstate Medical Center.

Sure, a lot of people may think marijuana isn’t so bad…but think again. At an Oct. 11 seminar at Duke’s Center on Addiction & Behavior Change, Dow-Edwards enlightened those who attended with correlations between smoking the reefer and things like IQ, psychosis and memory.

(https://media.makeameme.org/created/Littering-and-SMOKIN.jpg)

Dow-Edwards is currently a professor of physiology and pharmacology and clearly knows her stuff. She was throwing complicated graphs and large studies at us, all backing up her primary claim: the “dose-response relationship.” Basically the more you smoke (“dose”), the more of a biological effect it will have on you (“response”).

Looking at pot users after adolescence showed that occasionally smoking did not cause a big change in IQ, and frequently smoking affected IQ a little. However, looking at adults who smoked during adolescence correlated to a huge drop of around 7 IQ points for infrequent smokers and 10 points for frequent smokers. Here we see how both age and frequency play a role in weed’s effect on cognition. So if you are going to make the choice to light up, maybe wait until your executive functions mature around 24 years old.

Smoking weed earlier in life also showed a strong correlation with an earlier onset of psychosis, a very serious mental disorder in which you start to lose sense of reality. Definitely not good. I’m not trynna get diagnosed with psychosis any time soon!

One perhaps encouraging study for you smokers out there was that marijuana really had no effect on long-term memory. Non-smokers were better at verbal learning than heavy smokers…until after a three week abstinence break, where the heavy smokers’ memories recovered to match the control groups’. So while smoking weed when you have a test coming up maybe isn’t the best idea, there’s not necessarily a need to fear in the long run.

(Hanson et al, 2010)

A similar study showed that signs of depression and anxiety also normalized after 28 days of not smoking. Don’t get too hyped though, because even after the abstinence period, there was still “persistent impulsivity and reduced reward responses,” as well as a drop in attention accuracy.

A common belief about weed is that it is not addicting, but it actually is. What happens is that after repetitively smoking, feeling high no longer equates to feeling better than normal, but rather being sober equates to feeling worse than normal. This can lead to irritability, reduced appetite, and sleeplessness. Up to 1/2 of teens who smoke pot daily become dependent, and in broader terms, 9 percent of people who just experiment become dependent.

In summary, “marijuana interferes with normal brain development and maturation.” While it’s not going to kill you, it does effect your cognitive functions. Plus, you are at a higher risk for mental disorders like psychosis and future dependence. So choose wisely, my friends.

By Will Sheehan

Will Sheehan

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