Especialistas falam da maior ocorrência de catástrofes naturais

Os fenômenos climáticos estão ficando mais extremos: só na tragédia da Região Serrana do Rio, o número de vítimas já é maior do que todas as mortes causadas pela chuva em 2010

Catástrofes naturais como essa que estamos vendo na Região Sudeste têm se tornado cada vez mais comuns e mais intensas. A equipe do Bom Dia Brasil em São Paulo ouviu especialistas. Há anos a gente ouve alertas de cientistas de que o clima está mudando.

Os fenômenos climáticos estão ficando mais extremos.Há uma trágica mistura de fatores que faz o número de mortos aumentar exponencialmente, ano a ano. Muitas vezes não há interesse em desocupar áreas de risco porque isso pode tirar votos de políticos profissionais.

E poder público gasta hoje treze vezes mais para recuperar áreas atingidas por desastres naturais do que para prevenir as tragédias.

Um levantamento do Ministério da Integração Nacional mostra que 473 pessoas morreram no Brasil em 2010, atingidas de alguma forma pela chuva. Só este mês, na tragédia na Região Serrana do Rio de Janeiro, o número de vítimas já passou disso. E o volume de água trazido pela chuva também está aumentando.

“Na Região Metropolitana de São Paulo até a década de 1950, nós não observávamos chuvas fortes, chuvas intensas, ou seja, chuva com volume superior a 100 milímetros por dia. Hoje nós observamos cerca de cinco casos por ano. Para se ter uma ideia, chuvas acima de 30 milímetros por dia são suficientes para causar enchentes. É esse quadro que deve se intensificar, inclusive nos próximos anos, em virtude também do aquecimento global”, acrescenta o pesquisador do Inpe, Gilvan Sampaio.

Durante todo o ano passado, o Governo Federal usou com obras de prevenção e preparação para desastres R$ 167,5 milhões, segundo a ONG Contas Abertas, que acompanha os investimentos públicos. Só para recuperar os estragos provocados pelos desastres, foram R$ 2 bilhões, um gasto quase 13 vezes maior.

Para o professor de ciência política da Fundação Getúlio Vargas (FGV), Fernando Abrucio, o poder público deveria unir forças num programa nacional de prevenção, inclusive com a parceria do setor privado para reurbanizar as áreas de risco e garantir moradia para as famílias que tiverem de deixar esses locais.

“Eu acho que três pontos são fundamentais em um governo preventivo. Primeiro: uma articulação continua entre os três níveis de governo, segundo uma articulação continua entre os três níveis de governo; segundo, uma articulação contínua os governos Executivo, Judiciário e Legislativo e Ministério Público, para que se possa ter, de fato, ações sobre os problemas. E por fim, para ter um bom governo preventivo é preciso se ter uma articulação muito forte entre estado e sociedade. O Estado sozinho não vai ser capaz de prevenir as tragédias”, observa o cientista político Fernando Abrucio.

O geólogo do Instituto de Pesquisas Tecnológicas (IPT), Eduardo Macedo, lembra que essas mudanças levam tempo para acontecer. Enquanto isso, é preciso investir pesado nos sistemas de alerta para a retirada dos moradores das áreas de risco quando houver uma ameaça.

“Hoje uma reurbanização de favelas custa, pelo menos, de R$ 50 milhões a R$ 100 milhões. Só São Paulo tem 1,6 mil favelas. Basta fazer as contas e ver que a quantidade de dinheiro é muito grande. Nós vamos levar muito tempo para resolver isso, talvez uma próxima geração veja esse problema resolvido. Só que você pode trabalhar a questão da previsão e da convivência com o problema. Ao menos, as pessoas podem conviver e perder suas casas, mas não perdem o principal, que é a vida”, afirma o geólogo do IPT, Eduardo Macedo.

O último mapeamento das áreas de risco em São Paulo foi feito há sete anos, e apontava 562 pontos perigosos na cidade, sendo 300 de alto risco. Um novo levantamento deve ser divulgado na próxima semana, um mês depois do início do verão.

Argentina está vigilante pela ameaça de dengue, gripe A (H1N1) e sarampo

Calcula-se que haja 1 milhão de infectados só de dengue na fronteira com o Brasil e o Paraguai

BUENOS AIRES - Autoridades sanitárias da Argentina reiteraram nesta quinta-feira, 13, alertas à população para prevenir contágios de dengue, doença em proliferação na fronteira com o Brasil e o Paraguai, onde calcula-se que haja 1 milhão de infectados.

Outra preocupação do governo do país vizinho é sobre o contágio de sarampo e gripe A (H1N1), depois da detecção de que viajantes procedentes de países europeus contraíram essas doenças.

A dengue é uma ameaça latente no nordeste da Argentina, zona subtropical na fronteira com o Paraguai e o Brasil, insistiu Alejandro Collia, ministro da Saúde da província de Buenos Aires, onde reside cerca de um terço dos 40 milhões de argentinos.

"É preciso usar repelente de insetos e calça comprida, principalmente no início da manhã e no entardecer, que é quando o mosquito que transmite a dengue costuma atacar", disse o político à rádio portenha Continental.

Collia estima que no Paraguai e Brasil haja 1 milhão de pessoas contaminadas pela dengue, que em 2009 infectou cerca de 50 mil argentinos e causou cerca de dez mortos. Ele ressaltou que "não se devem tomar aspirinas", porque o remédio favorece hemorragias provocadas pela doença, transmitida pelo Aedes aegypti.

O ministro advertiu que as pessoas que viajarem à Europa devem tomar precauções para evitar contágios de sarampo e gripe A (H1N1), isso porque recentemente indivíduos que retornaram da Bélgica, Inglaterra e Suécia estavam infectados.

Collia repetiu as recomendações de evitar aglomerações e manter as mãos limpas para prevenir a gripe A (H1N1), que em 2009 causou 500 mortes e 10 mil contaminações. A proliferação obrigou a suspensão das aulas em escolas e universidades de 17 das 23 províncias argentinas.

Já o sarampo "voltou a zero" na Argentina, depois que a doença retornou ao país no ano passado pelo contágio de torcedores que foram à Copa do Mundo da África do Sul. As advertências de Collia estão em sintonia com as feitas há poucos dias pelo ministro de Saúde argentino, Juan Manzur, que assegurou que "o sistema de alarme sanitário do país funciona".

Cientistas modificam frangos para que não desenvolvam gripe aviária

Alteração genética 'engana' vírus, que não consegue se reproduzir. Animais chegam a ficar doentes, mas não transmitem a gripe.

Cientistas das universidades de Cambridge e Edimburgo desenvolveram uma técnica para modificar geneticamente os frangos para que não transmitam a gripe aviária, de acordo com um estudo publicado pela revista "Science".

A gripe aviária, também conhecida como vírus H5N1, geralmente atinge as aves de criação, mas também pode afetar pessoas, causando graves problemas respiratórios e outras complicações derivadas.

"As aves são uma espécie que pode criar novas formas de gripe, que podem ser transmitidas aos humanos", explica Laurence Tiley, do departamento de Veterinária da Universidade de Cambridge.Os primeiros casos de gripe aviária em humanos foram detectados em Hong Kong, em 1997, mas desde 2004, quando ocorreu uma epidemia global, foram registrados casos por todo mundo.

A pesquisa se baseia na alteração de um novo gene que recria uma molécula chamariz, que, por sua vez, imita um elemento da gripe aviária. "O vírus é enganado para que reconheça a molécula ao invés do genoma viral, o que interfere na duplicação do ciclo do vírus", segundo o estudo.

Quando os cientistas infectam as aves geneticamente modificadas com a gripe aviária, os animais ficam doentes, mas não contagiam outras aves, sejam estas modificadas geneticamente ou não.

Impacto econômico

"A prevenção da transmissão do vírus nas aves deve reduzir economicamente o impacto desta doença, assim como o risco que implica as pessoas estarem expostas aos indivíduos infectados", assegura a especialista.

No entanto, Tiley enfatiza que a pesquisa se encontra numa fase preliminar e que as aves criadas ainda não serão destinadas ao consumo. "A modificação genética que estudamos é um primeiro passo muito significativo do caminho para desenvolver aves que sejam completamente imunes à gripe aviária", assinala Tiley.

"O resultado obtido pelo estudo é muito animador", assegura a pesquisadora Helen Sang, da Universidade de Edimburgo.

"A utilização da modificação genética para introduzir mudanças genéticas que não podem ser obtidos mediante a reprodução animal demonstra o potencial da modificação genética para melhorar o estado dos animais na indústria aviária", afirma Sang.

"Este trabalho pode ser também a base para melhorar a economia e a segurança alimentar em muitas regiões do mundo onde a gripe aviária é um problema significativo", prossegue.

Enzyme Inhibition or Removal May Prevent or Treat Ischemic Retinopathy

ScienceDaily (Jan. 13, 2011) — The inhibition or removal of an enzyme may prevent or treat ischemic retinopathy by stalling growth of unwanted vessels in the retina, Medical College of Georgia researchers say.

Dr. Mohamed Al-Shabrawey, MCG assistant professor of oral biology, anatomy and ophthalmology, found that the inhibition or removal of an enzyme may prevent or treat ischemic retinopathy by stalling growth of unwanted vessels in the retina

Ischemic retinopathy is characterized by uncontrolled formation of new blood vessels in the retina, and is seen in diseases such as diabetic retinopathy and retinopathy of prematurity. While this blood vessel formation, called neovascularization, can benefit ischemic heart disease and wound healing, it is bad in the retina, where new vessels are dysfunctional and bleed, usually ending in retinal detachment.

Retinal neovascularization is controlled by a balancing act between pigment epithelium derived factor, the "good guy," and its nemesis, vascular endothelial growth factor.

"We wanted to learn how the disruption of that balance occurs and how to prevent it," said Dr. Mohamed Al-Shabrawey, Assistant Professor of Oral Biology, Anatomy and Ophthalmology and corresponding author of the study published online in Diabetes.

Al-Shabrawey studied an inflammatory pathway that has been shown to induce expression of the bad growth factor. In that pathway, the enzyme 12-lipoxygenase converts arachidonic acid, which helps regulate neovascularization, into the product 12-hydroxyeicosatetraenoic acid, or 12-HETE. He hypothesized that 12-HETE is linked to retinal neovascularization.

The study found a significant increase in the expression of the enzyme and production of 12-HETE in humans with advanced-stage diabetic retinopathy and in animals with induced ischemic retinopathy.

Al-Shabrawey also treated retinal Müller cells in vitro with 12-HETE. He found this increased the amount of vascular endothelial growth factor and decreased pigment epithelium derived factor, disrupting the balance and leading to neovascularization.

Using this finding, Al-Shabrawey's team found that treating the animals with an enzyme inhibitor or inducing ischemic retinopathy in animals lacking the enzyme restored that balance and inhibited neovascularization.

"This led us to conclude that if we can target or inhibit this enzyme's pathway, we might be able to prevent or treat diseases of ischemic retinopathy," Al-Shabrawey said.

While this study focused on an end stage of the disease, the next step is to study how inhibiting the enzyme will affect earlier stages of vascular dysfunction.

The study was funded by the American Heart Association and an MCG intramural grant, and involved collaboration with investigators from MCG, Mansoura College of Medicine in Egypt, Northwestern University, University of Wisconsin and Wayne State University.

Scientists Sequence Gut Microbes of Premature Infant

ScienceDaily (Jan. 13, 2011) — Scientists have for the first time sequenced and reconstructed the genomes of most of the microbes in the gut of a premature newborn and documented how the microbe populations changed over time.

The microbes in the gut of a premature infant change radically from day 10 and days 16-21, as indicated by the colored bars keyed to different microbial groups. Even day to day, the relative proportions of microbes shifts, and probably continues to change as the baby encounters new environments, people and pets.

Further studies involving more infants could eventually help researchers understand the causes of various intestinal problems that afflict preemies, in particular the sometimes fatal necrotizing enterocolitis, according to researchers at the University of California, Berkeley, the University of Pittsburgh School of Medicine and Stanford University. One unresolved question is whether these illnesses are caused by pathogenic strains of bacteria or just an imbalance in the microbe populations in the gut.

The study was posted online Dec. 29 in advance of print publication in the journal Proceedings of the National Academy of Sciences.

While this is not the first time that microbes in the human intestinal tract have been sequenced as a community, this is the first comprehensive look at a time series documenting colonization of the gut of a premature newborn, and one of few completely assembled community genomic datasets, said Jill Banfield, a UC Berkeley professor of earth and planetary science and of environmental science, policy and management.

"Sequencing of microbial communities has become exceedingly common, but many researchers work with essentially unassembled data and often analyze very short contiguous DNA sequences -- genome fragments," she said. "We actually go in and work out where the assemblies failed and fix them -- what's called curating the data -- so we can build very complete genomes for most of the microbes."

From acid mines to the preemie gut

Pediatric surgeon Michael J. Morowitz, until recently at The University of Chicago Medical Center but now with Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center and an assistant professor of surgery at the University of Pittsburgh School of Medicine, first approached Banfield because of her pioneering work over the past decade sequencing microbial communities in extreme environments, such as the acid drainage from underground mines. He suggested that she tackle a unique human environment, the newborn intestinal tract. Unlike the adult gut, which may contain a couple of thousand microbial species, the newborn's intestinal tract may be colonized by only a handful, making it feasible to sequence the entire community.

His interest stemmed from work with premature infants, most of whom spend anywhere from two weeks to six months in the intensive care unit before they're deemed healthy enough to go home. Between 5 and 10 percent of these preemies develop symptoms of necrotizing enterocolitis (NEC), which requires rounds of antibiotics to halt, and perhaps a third of these babies eventually require surgery to remove parts of their intestines that have died.

"The actual impact of necrotizing enterocolitis in the ICU is even larger, because feeding routines and other care are conducted around a fear of NEC developing," Morowitz said.

Previous studies, however, have produced conflicting results about NEC's cause. Some have found pathogenic bacteria associated with NEC, while others have found no difference between the bacteria in babies with and without NEC. Banfield, Morowitz and their collaborators suspect that these results reflect the fact that researchers have looked broadly at species or families of bacteria in the gut, rather than at variants or strains. Although coexisting strains may have genes that are 99 percent identical, their genomes could be sufficiently distinct to make one bad and the other good.

"We already know that just a few genes can make one strain a pathogen and one beneficial or commensal," meaning that the microbes live amicably with their host, Banfield said. "We expect that a lot of the issues with the colonization process in the gut that leads to disease may be tracked to subtle differences in strains," she said. "So one question on the table is, 'Are these very closely related strains physiologically distinct, and in what ways'?"

The only way to get at these differences, she said, is to sequence the entire genomes of the intestinal microbiota -- not merely DNA fragments or short DNA tags, which can be used to identify the genus or even species of a microbe, but not the specific strain.

Colonizing the gut

"Although a primary target of our research is NEC, it's become very apparent that there are some fundamental unanswered questions just about the colonization process under normal circumstances," Morowitz added. "It's really important to get a handle on what the normal process is first, and then, eventually, we can look closely at babies with NEC and see if they deviate from what appears to be the normal colonization process."

Other human diseases, including asthma, diabetes and obesity, have been linked to problems with microbial colonization of the gut, and several papers have reported symptomatic improvement after "transplanting" fecal material from healthy individuals to patients with a range of intestinal disorders.

Banfield, Morowitz and their colleagues followed a single premature infant that had been delivered by cesarean and identified three distinct communities of intestinal microbes present at different times during the first month of the infant's life. The microbe populations in these communities seemed to change after alterations in medication and feeding, Morowitz said. Although it was presumably sterile at birth, the infant's gut was quickly colonized by a set of known intestinal microbes -- bacteria and Archaea, primarily, but also viruses, bacterial viruses (phage) and the naked lengths of DNA called plasmids. When the baby went off antibiotics and switched from breast feeding to intravenous feeding, the microbe populations completely changed, with minor microbial members suddenly dominating and dominant members declining.

Vincent Denef, a post-doctoral researcher in Banfield's lab who contributed to the study, noted that such real-time studies are powerful because "very rarely do we have the opportunity to observe the dynamics of a naturally occurring system, such as the infant GI tract, as it is transformed from sterile to functionally diverse."

The populations again shifted when intravenous feeding was replaced by formula. Morowitz stopped collecting feces from dirty diapers after 21 days, and the infant was sent home healthy after 9 weeks in the ICU.

Though fecal samples were taken nearly every day, a complete genome analysis was performed only for samples collected on days 10, 16, 18 and 21. For the other days, the microbial community was estimated based on DNA tags (16S rRNA) that identify microbe families and species, but not specific strains.

What distinguishes bad from good microbes?

What surprised the researchers is that the microbial population was comprised of members of at least 20 groups, many of which include harmful as well as benign organisms. These included Staphylococcus, a frequent cause of hospital infections; Pseudomonas, "the cause of an enormous amount of morbidity in ICU patients, both children and adults," Morowitz said; Serratia, a common cause of sepsis in general; and Citrobacter, which can cause meningitis in babies. Yet, the baby in this study appeared healthy throughout.

"The gut populations are highly dynamic, with large shifts through three stages over time, but we saw an overabundance of gram-negative organisms that we often associate with disease," he said. "Particularly striking was the dominance ofPseudomonas for several days, though the infant was clinically stable."

The seeming contradiction of a healthy infant with disease-causing bacteria in her gut could be explained if the strains in the infant's gut were benign, or if the balance of other microbes prevented pathogenic microbes from causing problems.

Citrobacter, for example, is one type of bacteria that is reportedly associated with NEC: one study found Citrobacter in three of four infants with NEC, but in no control infants. Yet, in the current study, sequencing of the gut microbiome on days 16, 18 and 21 revealed the presence of two strains ofCitrobacter, which fluctuated significantly in proportions on the three days. "Those big shifts could potentially have been very important for the medical state of that baby," Banfield said. "Fortunately, the baby was fine."

The researchers found that those two strains were 99 percent similar over areas of the genome that could be compared.

"Of particular interest were hot spots of rapid DNA evolution within and between genes. Those potentially could be very important and interesting," she said. "Though the twoCitrobacter genotypes are very, very similar over most of the genome, the results suggest that they could be functioning in different ways because their genomes are regulated differently."

Banfield noted that the intestinal community of the infant no doubt would continue to shift repeatedly for a year or more after birth, as the child encounters new microbes -- courtesy of family, friends and pets. These populations shift with the influx of new strains and species and potentially because the resident microbes themselves evolve by picking up new traits from the plasmids and phages living alongside them.

"This is an ecological study," she emphasized. "One of the things we are trying to do is bring into the field of medicine a high resolution, ecological approach."

Other coauthors of the study are Brian C. Thomas of UC Berkeley, Valeriy Poroykoa of the University of Chicago Pritzker School of Medicine, and David A. Relman and Elizabeth K. Costello of the Stanford University School of Medicine.

The work was funded by National Institute of Allergy and Infectious Diseases of the National Institutes of Health, the Department of Energy, the Surgical Infection Society and The March of Dimes.

New Measure Trumps High-Density Lipoprotein (HDL) Levels in Protecting Against Heart Disease

ScienceDaily (Jan. 13, 2011) — The discovery that high levels of high-density lipoprotein (HDL) cholesterol (the "good cholesterol") is associated with reduced risk of cardiovascular disease has fostered intensive research to modify HDL levels for therapeutic gain. However, recent findings have called into question the notion that pharmacologic increases in HDL cholesterol levels are necessarily beneficial to patients. Now, a new study from researchers at the University of Pennsylvania School of Medicine shows that a different metric, a measure of HDL function called cholesterol efflux capacity, is more closely associated with protection against heart disease than HDL cholesterol levels themselves.

Findings from the study could lead to new therapeutic interventions in the fight against heart disease. The new research will be published in the January 13 issue of the New England Journal of Medicine.

Atherosclerosis, a component of heart disease, occurs with a build-up along the artery wall of fatty materials such as cholesterol. Cholesterol efflux capacity, an integrated measure of HDL function, is a direct measure of the efficiency by which a person's HDL removes cholesterol from cholesterol-loaded macrophages (a type of white blood cell), the sort that accumulate in arterial plaque.

"Recent scientific findings have directed increasing interest toward the concept that measures of the function of HDL, rather than simply its level in the blood, might be more important to assessing cardiovascular risk and evaluating new HDL-targeted therapies," said Daniel J. Rader, MD, director, Preventive Cardiology at Penn. "Our study is the first to relate a measure of HDL function--its ability to remove cholesterol from macrophages--to measures of cardiovascular disease in a large number of people."

In the present study, Rader and colleagues at Penn measured cholesterol efflux capacity in 203 healthy volunteers who underwent assessment of carotid artery intima-media thickness, a measure of arthrosclerosis, 442 patients with confirmed coronary artery disease, and 351 patients without such confirmed disease.

An inverse relationship was noted between cholesterol efflux capacity and carotid intima-media thickness both before and after adjustment for the HDL cholesterol level. After an age- and gender- adjusted analysis, increasing efflux capacity conferred decreased likelihood of having coronary artery disease. This relationship remained robust after the addition of traditional cardiovascular risk factors, including HDL cholesterol levels, as covariates. Additionally, men and current smokers had decreased efflux capacity.

The researchers noted that although cholesterol efflux from macrophages represents only a small fraction of overall flow through the cholesterol pathway, it is probably the component that is most relevant to protection against heart disease.

Rader said, "The findings from this study support the concept that measurement of HDL function provides information beyond that of HDL level, and suggests the potential for wider use of this measure of HDL function in the assessment of new HDL therapies. Future studies may prove fruitful in elucidating additional HDL components that determine cholesterol efflux capacity."

This work was funded in part by grants from the National Heart, Lung, and Blood Institute, the National Center for Research Resources, and a Distinguished Clinical Scientist Award from the Doris Duke Charitable Foundation.

Overexpression of Repetitive DNA Sequences Discovered in Common Tumor Cells

ScienceDaily (Jan. 13, 2011) — Massachusetts General Hospital (MGH) Cancer Center researchers have discovered a previously unknown feature of common tumor cells -- massive overexpression of certain DNA sequences that do not code for proteins. These DNA sequences -- called satellite repeats -- have been studied for their role in chromosomal structure but previously were not suspected of having a role in cancer. The report will appear in the journal Science and is receiving early online release.

"Satellite repeats make up a large part of our genome but had been thought to be inactive," explains David Ting, MD, of the MGH Cancer Center, co-lead author of the Sciencepaper. "We found that these regions are, in fact, very active in cancer but not in normal tissue. The findings may give us a novel cancer biomarker, as well as new insights into how cancers behave."

Because previously available tools for analyzing the transcription of DNA into RNA were designed to focus on sequences that are eventually translated into proteins, they excluded segments present in multiple-repeat copies that do not produce proteins. Among these stretches of DNA are satellite repeats, repetitive sequences often found near the centers or the tips of chromosomes. Significant expression of satellite repeats had been seen previously only in embryonic tissues or embryonic stem cells.

The current study was designed to give a more comprehensive picture of the transcriptome -- the full range of RNA molecules -- of primary tumors. Using an advanced digital gene expression analysis system called single molecule next-generation sequencing, the MGH team first studied samples from a mouse model of pancreatic cancer and were surprised to find that satellite DNA was expressed at levels more than 100 times what would be expected in normal tissues. Greatly increased satellite expression was also found in mouse colon and lung tumors, and all the tested samples were epithelial cancers, the most common type of solid tumor.

Analysis of human tumor samples produced similar results, with powerful overexpression of two satellites called HSATII and ALR in the majority of cancers studied, including tumors of the pancreas, lung, prostate. Ting notes that finding increased satellite expression in lower-grade tumors suggested that overexpression begins early in tumor development, which has implications for early detection.

"Cancer diagnoses are increasingly being made on the basis of fine-needle biopsies, which yield small numbers of cells that must be correctly identified as malignant," he explains. "In a few of the analyzed samples, our team demonstrated that pancreatic cancer cells were correctly identified based on satellite RNA expression, which was appreciably higher than in nonmalignant cells. If confirmed in large prospective clinical trials, satellite RNA expression may provide a new and highly specific biomarker relevant to multiple types of epithelial cancers."

Daniel Haber, MD, PhD, director of the MGH Cancer Center and senior author of the Science paper, says, "What is most remarkable is how such a dramatic abnormality was only revealed because of new powerful sequencing technologies that allow us to study a type of RNA that was previously discarded. Our hope is that this abnormality will serve as an important biomarker in cancer diagnosis and that it will also shed light on common mechanisms by which cancer develops."

Haber is the Kurt J. Isselbacher/Peter D. Schwartz Professor of Oncology and Ting is an instructor in Medicine at Harvard Medical School. The co-lead author of the Science paper is Doron Lipson, PhD, of Helicos BioSciences Corporation, which manufactures the gene expression analysis technology used in this study. Additional co-authors are Suchismita Paul, Brian Brannigan, Sara Akhavanfard, MD, Erik J. Coffman, Gianmarco Contino, MD, Vikram Deshpande, MD, John Iafrate, MD, PhD, Miguel Rivera, MD, Nabeel Bardeesy, PhD, and Shyamala Maheswaran, PhD, MGH Cancer Center; and Stan Letovsky, PhD, Helicos BioSciences. The study was supported by grants from the Pancreatic Action Network/American Association for Cancer Research; the Warshaw Institute for Pancreatic Cancer Research at MGH, Fondacion Veronesi and the Howard Hughes Medical Institute.