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Monday, May 13th, 2019
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| 10:10a |
Caught between criminals and cops To a resume rich in policy and security studies, work experience, and publications, Andrew Miller may now add the unlikely skill of video production. While investigating the impact of gang violence on Lagos, Nigeria, the sixth-year political science doctoral candidate came up with an innovative research tool: immersive, virtual reality (VR) videos.
"This was the first time VR was deployed in a large-scale field survey," says Miller, a PhD candidate in the MIT Department of Political Science. "Using VR video vignettes, we could immerse respondents in hypothetical scenarios, which helped elicit their real-world emotions when answering questions about these scenarios."
Miller's foray into production evolved as part of his multi-year doctoral study into the ways criminal organizations wield influence in communities.
"Deaths from criminal violence likely equal deaths from civil war, terrorism, and interstate war combined," he says, "and those responsible often operate with quasi-impunity." In the Americas, for instance, for every 100 murders, only about 25 people are convicted, Miller notes. "It's not just a problem for developing countries; even in some major American cities, people who commit murder are much more likely to get away with it than be arrested or convicted."
Miller has a master's degree in foreign service and security from Georgetown University, and has held international development and security positions with Deloitte Consulting and the Council on Foreign Relations. After spending significant time on the ground in places like Iraq, Afghanistan, Bosnia, and Kosovo, he became keenly aware of "criminal organizations operating in many of these places under the surface," and of frequent collusion between criminal groups and governments.
"You could have a government with all the resources, the trappings of legitimacy and legal frameworks, and still have small, illegal organizations that exercise a surprising degree of control in communities," he says.
In the daily lives of citizens in so many of the places he visited, the most meaningful security issues involve "problems with underground economies, real or perceived corruption of the police, and threatened and actual violence by criminals trying to control these economies," Miller says.
Concerned by this pervasive problem, which is only likely to grow in significance as urban areas expand in population, Miller set out to investigate the relationships between citizens and law enforcement. He decided to focus specifically on how and why people in communities afflicted by gang violence decide to cooperate with police. "If someone sees a shooting or hears about somebody involved in a shooting, what determines if that person shares information with the police?" Miller wondered.
Trust issues
Hoping to develop a broadly applicable theory, Miller chose two very different locales as research sites: Lagos, Nigeria, and Baltimore, Maryland. The former, home to more than 10 million people and the economic and cultural hub of West Africa, has pockets of the city beset with groups that extort shopkeepers, along the lines of Sicily's mafia. Baltimore is afflicted with gang violence around drug trafficking and one of the highest murder rates in the United States. What unites both cities, says Miller, is "a strained relationship between many residents and the police.”
Miller began in Lagos, with its densely populated markets, to explore this distrust. His research had built-in constraints: He could not run real-world simulations of violent incidents to test witness responses.
So Miller devised the notion of VR vignettes played on mobile phones to engage subjects and make it a more realistic experience for them. Hiring a Lagos production team and actors, he filmed a series of staged fights, with more than a dozen variations changing the circumstances of the fight or police response. Shown these different videos, 1,025 people completed surveys about their willingness to share information with the police.
After 11 months in Nigeria, Miller has begun to glean insights from his fieldwork. Among them: The central constraint to reporting incidents to police is "a deep-seated perceived retaliation risk from gangs, which are regarded with both antipathy and fear," says Miller. (One possible remedy to this hurdle that he identified through his research: expanding access to anonymous police tip lines — not currently available in Lagos.)
His survey data also revealed that even if citizens witness police using excessive force, violating the rights of suspects, they still believe sharing information is important.
"It was surprising to me that, even in cases where police are widely perceived as corrupt, citizens hold an enduring faith in their ability to bring law and order, as long as it doesn't jeopardize personal safety," he says. "People show amazing resilience in the face of their problems."
Baltimore and beyond
Miller has now turned his focus to completing the Baltimore phase of research. He's donning his production hat once again — this time for video segments of local news stories designed for an online survey. Both the work in Lagos and Baltimore will feature in his thesis on cooperation between citizens and the police in communities with gangs.
Although Miller has given himself little time off, he managed to slip away to northern Italy recently and was able to indulge in his favorite pastimes of travel and food.
While he once pursued a future in development and humanitarian assistance, he has fully committed to a life in academia. "I really love digging into issues deeply, and I enjoy teaching, especially the undergraduates at MIT," he says. He also cites the fruitful support and friendships he found in the political science department "that proved instrumental at all stages of the research process, from developing ideas to writing up the results."
A faculty position in a comparable environment that enables him to continue this work would be ideal, says Miller. "It's important that my work both contributes to academic theory and is relevant to people's lives," he says. "People in the communities where I have been working have emphasized to me that research like this needs to be done, so I hope it will be useful." | | 2:59p |
Measuring chromosome imbalance could clarify cancer prognosis Most human cells have 23 pairs of chromosomes. Any deviation from this number can be fatal for cells, and several genetic disorders, such as Down syndrome, are caused by abnormal numbers of chromosomes.
For decades, biologists have also known that cancer cells often have too few or too many copies of some chromosomes, a state known as aneuploidy. In a new study of prostate cancer, researchers have found that higher levels of aneuploidy lead to much greater lethality risk among patients.
The findings suggest a possible way to more accurately predict patients’ prognosis, and could be used to alert doctors which patients might need to be treated more aggressively, says Angelika Amon, the Kathleen and Curtis Marble Professor in Cancer Research in the Department of Biology and a member of the Koch Institute for Integrative Cancer Research.
“To me, the exciting opportunity here is the ability to inform treatment, because prostate cancer is such a prevalent cancer,” says Amon, who co-led this study with Lorelei Mucci, an associate professor of epidemiology at the Harvard T.H. Chan School of Public Health.
Konrad Stopsack, a research associate at Memorial Sloan Kettering Cancer Center, is the lead author of the paper, which appears in the Proceedings of the National Academy of Sciences the week of May 13. Charles Whittaker, a Koch Institute research scientist; Travis Gerke, a member of the Moffitt Cancer Center; Massimo Loda, chair of pathology and laboratory medicine at New York Presbyterian/Weill Cornell Medicine; and Philip Kantoff, chair of medicine at Memorial Sloan Kettering; are also authors of the study.
Better predictions
Aneuploidy occurs when cells make errors sorting their chromosomes during cell division. When aneuploidy occurs in embryonic cells, it is almost always fatal to the organism. For human embryos, extra copies of any chromosome are lethal, with the exceptions of chromosome 21, which produces Down syndrome; chromosomes 13 and 18, which lead to developmental disorders known as Patau and Edwards syndromes; and the X and Y sex chromosomes. Extra copies of the sex chromosomes can cause various disorders but are not usually lethal.
Most cancers also show very high prevalence of aneuploidy, which poses a paradox: Why does aneuploidy impair normal cells’ ability to survive, while aneuploid tumor cells are able to grow uncontrollably? There is evidence that aneuploidy makes cancer cells more aggressive, but it has been difficult to definitively demonstrate that link because in most types of cancer nearly all tumors are aneuploid, making it difficult to perform comparisons.
Prostate cancer is an ideal model to explore the link between aneuploidy and cancer aggressiveness, Amon says, because, unlike most other solid tumors, many prostate cancers (25 percent) are not aneuploid or have only a few altered chromosomes. This allows researchers to more easily assess the impact of aneuploidy on cancer progression.
What made the study possible was a collection of prostate tumor samples from the Health Professionals Follow-up Study and Physicians’ Health Study, run by the Harvard T.H. Chan School of Public Health over the course of more than 30 years. The researchers had genetic sequencing information for these samples, as well as data on whether and when their prostate cancer had spread to other organs and whether they had died from the disease.
Led by Stopsack, the researchers came up with a way to calculate the degree of aneuploidy of each sample, by comparing the genetic sequences of those samples with aneuploidy data from prostate genomes in The Cancer Genome Atlas. They could then correlate aneuploidy with patient outcomes, and they found that patients with a higher degree of aneuploidy were five times more likely to die from the disease. This was true even after accounting for differences in Gleason score, a measure of how much the patient’s cells resemble cancer cells or normal cells under a microscope, which is currently used by doctors to determine severity of disease.
The findings suggest that measuring aneuploidy could offer additional information for doctors who are deciding how to treat patients with prostate cancer, Amon says.
“Prostate cancer is terribly overdiagnosed and terribly overtreated,” she says. “So many people have radical prostatectomies, which has significant impact on people’s lives. On the other hand, thousands of men die from prostate cancer every year. Assessing aneuploidy could be an additional way of helping to inform risk stratification and treatment, especially among people who have tumors with high Gleason scores and are therefore at higher risk of dying from their cancer.”
“When you’re looking for prognostic factors, you want to find something that goes beyond known factors like Gleason score and PSA [prostate-specific antigen],” says Bruce Trock, a professor of urology at Johns Hopkins School of Medicine, who was not involved in the research. “If this kind of test could be done right after a prostatectomy, it could give physicians information to help them decide what might be the best treatment course.”
Amon is now working with researchers from the Harvard T.H. Chan School of Public Health to explore whether aneuploidy can be reliably measured from small biopsy samples.
Aneuploidy and cancer aggressiveness
The researchers found that the chromosomes that are most commonly aneuploid in prostate tumors are chromosomes 7 and 8. They are now trying to identify specific genes located on those chromosomes that might help cancer cells to survive and spread, and they are also studying why some prostate cancers have higher levels of aneuploidy than others.
“This research highlights the strengths of interdisciplinary, team science approaches to tackle outstanding questions in prostate cancer,” Mucci says. “We plan to translate these findings clinically in prostate biopsy specimens and experimentally to understand why aneuploidy occurs in prostate tumors.”
Another type of cancer where most patients have low levels of aneuploidy is thyroid cancer, so Amon now hopes to study whether thyroid cancer patients with higher levels of aneuploidy also have higher death rates.
“A very small proportion of thyroid tumors is highly aggressive and lethal, and I’m starting to wonder whether those are the ones that have some aneuploidy,” she says.
The research was funded by the Koch Institute Dana Farber/Harvard Cancer Center Bridge Project and by the National Institutes of Health, including the Koch Institute Support (core) Grant. | | 11:59p |
How a declining environment affects populations Stable ecosystems occasionally experience events that cause widespread death — for example, bacteria in the human gut may be wiped out by antibiotics, or ocean life may be depleted by overfishing. A new study from MIT physicists reveals how these events affect dynamics between different species within a community.
In their studies, performed in bacteria, the researchers found that a species with a small population size under normal conditions can increase in abundance as conditions deteriorate. These findings are consistent with a theoretical model that had been previously developed but has been difficult to test in larger organisms.
“For a single species within a complex community, an increase in mortality doesn’t necessarily mean that the net effect is that you’re going to be harmed. It could be that although the mortality itself is not good for you, the fact that your competitor species are also experiencing an increase in mortality, and they may be more sensitive to it than you are, means that you could do better,” says Jeff Gore, an MIT associate professor of physics and the senior author of the study.
The findings in bacteria may also be applicable to larger organisms in real-world populations, which are much more difficult to study because it is usually impossible to control the conditions of the experiment the way researchers can with bacteria growing in a test tube.
“We think that this may be happening in complex communities in natural environments, but it’s hard to do the experiments that are necessary to really nail it down. Whereas in the context of the lab, we can make very clear measurements where you see this effect in a very obvious way,” Gore says.
Clare Abreu, an MIT graduate student, is the lead author of the study, which appeared in Nature Communications on May 9. Vilhelm Andersen Woltz, an MIT undergraduate, and Jonathan Friedman, a former MIT postdoc, are also authors of the paper.
Competition for resources
Microbial communities, such as those found in soil, oceans, or the human gut, usually contain thousands of different species. Gore’s lab is interested in studying the factors that determine which species are present in a given environment, and how the composition of those populations affect their functions, whether that’s cycling carbon in the ocean or helping each other resist antibiotic treatment in the gut.
By performing controlled experiments in the lab, Gore hopes to learn how different species interact with each other, and to test hypotheses that predict how populations respond to their environment. In 2013, he discovered early signs that warn of population collapse, in yeast, and he has also studied how different species of bacteria can protect each other against antibiotics.
“We’re using experimentally tractable, simple communities to try to determine the principles that determine which species can coexist, and how that changes in different environments,” Gore says.
To explore whether these experimental results might be applicable to larger communities, last year Gore and his colleagues published a paper in which they showed that interactions between pairs of species that compete for resources can be used to predict, with about 90 percent accuracy, the outcome when three of the species compete with each other.
In the new study, Gore and Abreu decided to see if they could use pairwise interactions to predict how trios of competing species would respond as environmental conditions deteriorate. To simulate this in the lab, the researchers used the process of dilution — that is, discarding a large percentage (ranging from 90 percent to 99.999999 percent) of the population at the end of each day and transferring the remainder to fresh resources. This could be analogous to real-world conditions such as overfishing or loss of habitat.
“We’re trying to get at the general question of how an increase in mortality might change the composition of a community,” Gore says.
The researchers studied combinations of five species of soil bacteria. In their experiments, in which they tested pairs of species at a time, they found a specific pattern that fit the predictions made by a classical model of species interactions, known as the Lotka-Volterra model.
According to this model, declining environmental conditions should favor faster growers. The researchers found that this was the case: Even in conditions where a slower grower originally dominated the population, as the dilution rate was increased, the populations shifted until eventually the faster grower either became the larger fraction of the population or took over completely. The final outcome depends on how strong each competitor is, as well as their relative abundance in the starting population.
The researchers also found that the results of the pairwise competitions could accurately predict what would happen when three species grew together in an environment with deteriorating conditions.
“This is an exciting advance in our understanding of microbial ecology,” says Sean Gibbons, an assistant professor at the Institute for Systems Biology, who was not involved in the research. “The observation that nonspecific mortality rates can alter competitive outcomes is surprising, although more work needs to be done to understand whether or not dilution is having a more nuanced effect on environmental conditions.”
Population models
The Lotka-Volterra model analyzed in this study was originally developed for interactions between larger organisms. Such models are easier to test in microbial populations because it is much easier to control experimental conditions for bacteria than for, say, deer living in a forest.
“There’s no particular reason to believe that the models are more applicable to microbes than they are to macroorganisms. It’s just that with microbes, we can study hundreds of these communities at a time, and turn the experimental knobs and make clear measurements,” Gore says. “With microorganisms, we can arrive at a clear understanding of when is it that these models are working and when is it that they’re not.”
Gore and his students are now studying how specific environmental changes, including changes in temperature and resources, can alter the composition of microbial communities. They are also working on experimentally manipulating populations that include more than two bacterial species.
The research was funded, in part, by the National Institutes of Health. |
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