Researchers at Harvard-affiliated Brigham and Women’s Hospital and Harvard Medical School have embarked on an ambitious study of the link among genetics, lifestyle, environment, and health that organizers hope will set the stage for a new generation of personalized disease analysis and medical care.The study, called OurGenes, OurHealth, OurCommunity, eventually wants to enroll 100,000 patients in a lengthy, longitudinal study of the causes of illness that could help link genetic background to lifestyle and environmental factors.The study stands on three key parts: patients’ health backgrounds, which are provided to researchers through existing health records, family histories, and medical questionnaires; their genetic profiles, which are provided through blood samples; and their health futures, which are mapped through access to clinical data as it accumulates.Christine Seidman, the study’s co-principal investigator, the Thomas W. Smith Professor of Medicine and professor of genetics at Harvard Medical School, and director of the Brigham’s Cardiovascular Genetics Center, said she views the study as a community effort in which Brigham medical workers and patients come together to help realize the promise of advances that have been made in recent years in understanding genes.The study, which is in an initial, yearlong pilot phase, is enrolling patients at six Brigham-affiliated sites. Because of the consent, family history, and questionnaire process, she said the OurGenes staff is using the trial period to ensure that data gathering does not interfere with the clinical purpose of patient visits and also to make sure the enrollment process itself is capturing the diversity of patients.So far, Seidman said, about 100 people have enrolled in the study. The participation rate is about 70 percent of those approached and asked if they’re interested. Instead of waiting for patients to come to the hospitals or clinics, Seidman said, patients with appointments are mailed information a couple of weeks in advance of their appointments so they are aware of the study before being asked to participate. The information that is collected will be kept private.Seidman said healthy patients are as important to the study as people with medical conditions. Those with one condition can be part of a control population for studies that look at others. “If you’re perfectly healthy, you’re as valuable to us as someone with a devastating condition,” Seidman said. “We all have risk for some disease and less risk for others.”Seidman sees the study as long running, since it will take years to get the patient population enrolled, and the plan is to follow patients through time and monitor health outcomes. The study will gather information on topics as diverse as patients’ smoking history, their exercise practices, sun exposure, and even where they grew up. Examples of questions that researchers are hoping to answer include whether specific genes, in combination with certain lifestyle or environmental factors, lead to greater health risks and whether certain drugs lead to adverse reactions in patients with specific genetic profiles. Though the study was launched only in June, researchers are already expressing interest in identifying a patient population that is taking statins, the popular cholesterol-lowering drug.The accumulated health data, when combined with stored blood samples for genetic analysis, will also aid future researchers, who will be able to begin studies quickly and more efficiently than if they had to begin recruiting subjects from scratch, Seidman said.Though other studies have been conducted examining the genetic background of disease, most of those have been aimed at specific ailments, specific populations, or specific genes. OurGenes is one of the first to examine such a large, diverse population for broad health and genetic trends.
Once thought to be a problem primarily in the developed world, cancer is now a leading cause of death and disability in poorer countries. Almost two-thirds of the 7.6 million cancer deaths in the world occur in low- and middle-income countries.A paper published in the Lancet asserts that the international community must now discard the notion that cancer is a disease of the rich and instead approach it as a global health priority. This call to action paper is authored by Julio Frenk, dean of the Harvard School of Public Health (HSPH); Felicia Knaul, director of the Harvard Global Equity Initiative (HGEI) and HMS associate professor of social medicine; Paul Farmer, chair of the HMS department of global health and social medicine; and Lawrence Shulman, chief medical officer at Dana-Farber Cancer Institute (DFCI) and HMS associate professor of medicine at DFCI.Additional authors comprise 19 other leaders from the global health and cancer communities representing the Global Task Force on Expanded Access to Cancer Care and Control in Developing Countries (GTF.CCC), including honorary co-Presidents Lance Armstrong and HRH Princess Dina Mired of Jordan. GTF.CCC was launched in November of 2009 by HMS, HSPH, HGEI and DFCI.Link to Lancet abstract
The Bill & Melinda Gates Foundation announced the winners of Round 6 of its Grand Challenges Explorations initiative. Daniel G. Kavanagh, a member of the faculty at the Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, is one of 88 recipients of these $100,000 grants, which fund research to benefit global health and development.Grand Challenges Explorations funds scientists and researchers worldwide to explore ideas that can break the mold in how we solve persistent global health and development challenges.To receive funding, Kavanagh and other winners demonstrated in a two-page online application a bold idea in one of five critical global heath and development topic areas: polio eradication, HIV, sanitation, family health technologies, and mobile health. The project supported by this award — “Identification of Candidate Markers of HIV Latency” — will develop new methods to detect and characterize rare cells that are latently infected with HIV in patients on antiretroviral drug treatment.
By nestling quantum dots in an insulating egg-crate structure, researchers at the Harvard School of Engineering and Applied Sciences (SEAS) have demonstrated a robust new architecture for quantum-dot light-emitting devices (QD-LEDs).Quantum dots are very tiny crystals that glow with bright, rich colors when stimulated by an electric current. QD-LEDs are expected to find applications in television and computer screens, general light sources, and lasers.Previous work in the field had been complicated by organic molecules called ligands that dangle from the surface of the quantum dots. The ligands play an essential role in quantum dot formation, but they can cause functional problems later on.Thanks to an inventive change in technique devised by the Harvard team, the once-troublesome ligands can now be used to build a more versatile QD-LED structure. The new single-layer design, described in the October issue of the journal Advanced Materials, can withstand the use of chemical treatments to optimize the device’s performance for diverse applications.“With quantum dots, the chemical environment that’s optimal for growth is usually not the environment that’s optimal for function,” says co-principal investigator Venkatesh Narayanamurti, Benjamin Peirce Professor of Technology and Public Policy at SEAS.The quantum dots, each only 6 nanometers in diameter, are grown in a solution that glows strikingly under a black light.The solution of quantum dots can be deposited onto the surface of the electrodes using a range of techniques, but according to lead author Edward Likovich, who conducted the research as a Graduate School of Arts and Sciences doctoral candidate in applied physics at SEAS, “That’s when it gets complicated.”“The core of the dots is a perfect lattice of semiconductor material, but on the exterior it’s a lot messier,” he says. “The dots are coated with ligands, long organic chains that are necessary for precise synthesis of the dots in solution. But once you deposit the quantum dots onto the electrode surface, these same ligands make many of the typical device processing steps very difficult.”The ligands can interfere with current conduction, and attempts to modify them can cause the quantum dots to fuse together, destroying the properties that make them useful. Organic molecules can also degrade over time when exposed to UV rays.Researchers would like to be able to use those ligands to produce the quantum dots in solution, while minimizing the negative impact of the ligands on current conduction.“The QD technologies that have been developed so far are these big, thick, multilayer devices,” says co-author Rafael Jaramillo, a Ziff Environmental Fellow at the Harvard University Center for the Environment. Jaramillo works in the lab of Shriram Ramanathan, associate professor of materials science at SEAS.“Until now, those multiple layers have been essential for producing enough light, but they don’t allow much control over current conduction or flexibility in terms of chemical treatments,” says Jaramillo. “A thin, monolayer film of quantum dots is of tremendous interest in this field, because it enables so many new applications.”The new QD-LED resembles a sandwich, with a single active layer of quantum dots nestled in insulation and trapped between two ceramic electrodes. To create light, current must be funneled through the quantum dots, but the dots also have to be kept apart from one another in order to function.In an early design, the path of least resistance was between the quantum dots, so the electric current bypassed the dots and produced no light.Abandoning the traditional evaporation technique they had been using to apply insulation to the device, the researchers instead used atomic layer deposition (ALD) — a technique that involves jets of water. ALD takes advantage of the water-resistant ligands on the quantum dots, so when the aluminum oxide insulation is applied to the surface, it selectively fills the gaps between the dots, producing a flat surface on the top.The new structure allows more effective control over the flow of electrical current.“Exploiting these hydrophobic ligands allowed us to insulate the interstices between the quantum dots, essentially creating a structure that acts as an egg crate for quantum dots,” says co-author Kasey Russell, a postdoctoral fellow at SEAS. “The benefit is that we can funnel current directly through the quantum dots despite having only a single layer of them, and because we have that single layer, we can apply new chemical treatments to it, moving forward.”Through Harvard’s Office of Technology Development, Likovich and his colleagues have applied for a provisional patent on the device. Beyond the possible applications in computer and TV displays, lights, and lasers, the technology could one day be used in field-effect transistors or solar cells.The research was supported by the Harvard University Center for the Environment and the Nanoscale Science and Engineering Center at Harvard, which is funded by the National Science Foundation (NSF), and by the use of facilities at the Harvard University Center for Nanoscale Systems, a member of the NSF-supported National Nanotechnology Infrastructure Network.
One of the many student-led musical groups on campus, The Nostalgics keep a Detroit sound tradition alive as Harvard’s Motown and soul band. Recently, the group won Harvard’s battle of the bands competition. As its prize, the group played at the House of Blues in Boston at an inter-House formal involving Quincy, Leverett, Dunster, Cabot, and Currier Houses
Tunisian artist eL Seed took his spray paints out into the cold last week to create an example of “calligraffiti” in the Science Center’s plaza. The canvas featured the eponymous Arabic phrase in stylized black and gray whorls over a field of purples.The French-born artist completed the work, which he called “Taking Back the Purple,” in five hours.“For those of us who are nonartists, it is a really amazing thing to go from a blank canvas to a descriptive and deep collage of thought and color,” said Paul Beran, director of the Outreach Center at the Center for Middle Eastern Studies (CMES).EL Seed describes his work as occupying a middle ground between classical Arabic calligraphy and action painting. He first used calligraphy to help connect with his own Arab identity. Failing to find a teacher, eL Seed studied on his own. His lack of formal education in calligraphy, coupled with the intuitive, reflexive movements encouraged by spray painting, led him toward a freer approach to shape and color.But he is not satisfied with merely creating beautiful works.“You have to be a kind of ‘artivist,’ an artist and an activist at the same time,” he said. “And I believe that is the duty of art: to speak what other people do not want to speak. Say loudly what other people don’t want to say.”The conditions in the streets that help him speak so loudly sometimes dictate changes in his artistic plan. Last week, one can of gray began to change color in midspray, prompting a consult with another graffiti artist in the audience. When the wind whipped the canvas too violently to continue, eL Seed would break to speak to his audience in English, French, and Arabic. The artist took those opportunities to thaw his cold, bare, paint-covered fingers, but also to discuss the current political situation in Tunisia.“They say that artists create revolutions, but in Tunisia it was the contrary: The revolution created the artists.”EL Seed drew inspiration for his work from a visit to Tunisia in December. He was there to paint a mural in Kairouan commemorating the one-year anniversary of the Tunisian uprising. The locals supported his project but begged him not to use purple, which had been the color of former ruler Ben Ali’s regime. Sensitive to the political weight of the color, eL Seed obliged, but later reconsidered his stance.“Just as the people take back their freedom of speech, as an artist, I need to take back this color.”He sees his art as a vector for change, hoping that viewers develop a feeling of taking back what is theirs. He told many stories of popular participation in December’s project, describing citizens who had “never picked up a can” of paint joining him for up to eight days of work. Now, some of those street-art novices are painting their own murals. That artistic initiative, said eL Seed, instills a sense of pride that bodes well for the future of Tunisia.“That is the proof of a participatory democracy,” said eL Seed, “when you involve the people in a project.”While eL Seed was the only one to wield the spray can last week, he had what amounted to an artistic consultant in the crowd. Tamer Sameer, a Saudi Arabian street artist who studies at the University of Massachusetts, Boston, stepped forward to advise eL Seed how to resolve a few wind-influenced lines. Sameer took the work’s political message to heart.“He is like a guide to me,” said Sameer. “When I return to my city, I’d like to cover all the walls like this.”
The poor are disproportionately afflicted with a wide range of health problems, including heart disease, type 2 diabetes, asthma, infant mortality, and dental disease. Sleep deficiency and disorders including sleep apnea also are particularly common among minority groups and those from economically disadvantaged backgrounds, according to Harvard School of Public Health’s Michelle Williams, Stephen B. Kay Family Professor of Public Health and chair of the Department of Epidemiology. Sleep apnea causes breathing to briefly stop during sleep and can elevate risks for serious health problems, including heart failure and pregnancy complications. In an August 28, 2012 article on the Huffington Post, co-written by Harvard Medical School’s Susan Redline, Williams writes that the high prevalence of sleep apnea among the poor may be caused by exposure to air pollution, which can cause inflammation in the tissues near the throat. Read Full Story
A new rapid test for tuberculosis (TB) could substantially and cost-effectively reduce TB deaths and improve treatment in southern Africa — a region where both HIV and tuberculosis are common — according to a new study by Harvard School of Public Health (HSPH) researchers.“This test is one of the most significant developments in TB control options in many years,” said lead author Nicolas Menzies, a Ph.D. candidate in health policy working at HSPH. “Our study is the first to look at the long-term consequences of this test when incorporated into routine health programs.”The study appears online in PLOS Medicine after 5 p.m. today.Tuberculosis is an infectious disease that kills more than 1.5 million people annually — primarily in low- and middle-income countries. An estimated 9 million people developed the disease in 2010. HIV-infected patients are particularly vulnerable to TB, which is spread through airborne droplets when people with active disease cough or sneeze.Rapid and accurate diagnosis is key to preventing the spread of the disease. The World Health Organization (WHO) recently recommended the use of Xpert, an automated DNA test that can show a result within two hours, for people at high risk of multi-drug-resistant TB and/or HIV-associated TB. Many countries are already moving to adopt the test.Menzies, senior author and professor of global health at HSPH Joshua Salomon, and colleagues conducted a modeling study to investigate the potential health and economic consequences of implementing the Xpert test in Botswana, Lesotho, Namibia, South Africa, and Swaziland. They found that replacing the current diagnostic approach (which relies on identifying TB in patient’s sputum using a microscope) with one based on the Xpert test would prevent an estimated 132,000 TB cases and 182,000 TB deaths in southern Africa over 10 years, reducing by 28 percent the proportion of the population with active TB.The researchers estimated that the cost of widespread implementation of the Xpert test in southern Africa would be $460 million over the next 10 years, with the majority of these additional costs arising from increased utilization of TB and HIV treatment services. In particular, as the new test provides information on TB drug resistance, many more patients would be referred for treatment of multi-drug-resistant TB, which is expensive in this setting. The additional HIV treatment costs are a result of the success of the intervention — as individuals co-infected with TB and HIV receive better TB care, their survival improves, increasing the total number of people receiving HIV treatment.Taking into account both the additional costs and the health benefits from use of the new technology, adoption of the Xpert test in southern Africa would be a good value for the money, according to WHO standards. The researchers found that the cost per year of healthy life gained from adopting the new test ranged from $792 in Swaziland to $1,257 in Botswana. While these results suggest that scaling up Xpert can be a good health investment, the cost per healthy year gained is substantially higher in this study than in previous reports, and the economic results raise questions about affordability that will be critical for policymakers to consider.Menzies also cautioned that the study’s findings may not be applicable elsewhere, and that other countries may find more cost-effective interventions than Xpert to adopt first. “Given the fundamental influence of HIV on TB dynamics and intervention costs, care should be taken when interpreting the results of this analysis outside of settings with high HIV prevalence,” he said.Support for the study was provided in part by UNITAID and a training grant from the Harvard-affiliated Massachusetts General Hospital’s Program in Cancer Outcomes and Training.
The Harvard Initiative for Learning and Teaching (HILT) has issued a call for Spark Grant applications. Roughly five awards ranging from $5,000 to $15,000 will be given to ideas that “spark” promising teaching and learning projects from idea to reality, and positions innovations for future success. Harvard faculty, students, and staff are encouraged to apply.Although HILT welcomes any proposals that catalyze innovation around teaching and learning at Harvard, grant propsals that focus on the following are particularly encouraged:multimedia and instructional technology developmentcommunities of practice around teaching and learninghigh-impact course renewalassessment and educational researchApplications are due by July 22. Awards will be announced in early September with funding transferred shortly thereafter.Interested individuals can apply here. More information is available at: http://hilt.harvard.edu/pages/spark-grants
The Rafflesiaceae family of plants has many identities — producer of the largest flowers in the world, for one, with some specimens measuring a meter or more in diameter. They’re also known as “corpse flowers” because they give off an overwhelming odor of rotting flesh to attract pollinating insects. In their native Southeast Asia, they’re sometimes called the “jewel of Borneo” and are celebrated as a cultural touchstone and beacon for the conservation of the tropical rain forest.For scientists like Charles Davis, a professor of organismic and evolutionary biology, however, the plants have — until now — largely been known for their mysterious nature.The plants were described some 200 years ago, but botanists had been unable to answer many basic questions about them, particularly how those huge flowers develop. Using a combination of traditional methods and modern genetic testing to compare two closely related members of the family, Rafflesia and Sapria, a team of Harvard researchers — Davis, Lachezar Nikolov, a recent Ph.D. student in Davis’ lab, and Elena Kramer, the Bussey Professor of Organismic and Evolutionary Biology — is helping to provide key insights. The research, in collaboration with colleagues from Switzerland, Malaysia, and Thailand, is described in a paper published online Oct. 28 in the Proceedings of the National Academy of Sciences.“What I think is most striking is that these two plants, which look nearly identical, are built in fundamentally different ways,” Davis said. “Rafflesia have been described for almost 200 years, by some of the best morphologists, but the basic understanding of their floral organs was not known until now.”Outwardly, Davis said, Sapria and Rafflesia produce nearly identical chamber-shaped blossoms. They are characterized by similar structures — each includes a number of outer “lobes” resembling petals on flowers, with a center dominated by a domelike structure, called a diaphragm, that encloses a central disk containing the plant’s reproductive structures. One of the few outward contrasts between Rafflesia and Sapria, Davis said, is the number of lobes — Sapria has 10 or more, Rafflesia just five.A closer look, however, revealed vast differences in structures that appear very similar.Careful inspection using traditional microscopy and cutting-edge genetic methods performed first in Sapria showed that it is constructed like many flowers. The lobes on its outer ring are the plant’s sepals — the outermost part that forms a flower — while the inner lobes are petals. Perhaps most importantly, Davis said, tests showed that the diaphragm is a separate structure.In Rafflesia, meanwhile, researchers found something distinctly different that provided a breakthrough. “Like Sapria, we think the single outer lobes are sepals,” Davis said. “When we look at Rafflesia in the early stages of development, however, the petals are very different. We find that they have become fused to form the diaphragm. No one had ever looked carefully at this early stage of Rafflesia development to connect these outer lobes to sepals, and the inner lobes to the bizarre diaphragm structure.”Researchers also uncovered a novel ringlike organ, distinct from the petals and sepals, that circled the inside of both plants. This type of organ is what gives daffodils their trumpets, and passionflowers their crowns. In Rafflesia, Davis said, the structure was prominent early in the plant’s development, but never developed beyond that point. By contrast, the structure was found to be critical in Sapria, where it expands dramatically to form the inner walls of the flower’s chamber and its domelike diaphragm.The results were so surprising, Davis said, that he initially didn’t believe them.“It was hard to imagine,” he said. “These plants look very similar, yet they’re built in fundamentally different ways.”While the study sheds new light on how these plants develop, Davis said it may also help to explain how Rafflesia in particular attained such huge flowers. “Among a very large flowered group of plants, Rafflesia’s have the biggest flowers of them all!” Davis says.“Based on what we know about the development of other, related plants, we believe Sapria represents the more ancestral pattern of construction,” Davis said. “If you look at the evolution of Rafflesia, which contains the biggest flowers within the family, we see a major burst in floral size, so it may be that this re-architecture is what allowed these plants to become even larger.”