On Saturday night, Pigeons Playing Ping Pong played the first show of their sold-out two-night stand at Port City Music Hall this weekend. By the time Vermont jam band Swimmer opened the show, the room was already filling up. By the time Pigeons came on it was as crowded as the Portland, Maine venue could possibly manage, the audience fully invested and singing along all night.The band responded in kind with a fantastic show including highlights like an inverted “Psycho Killer” (Talking Heads) segment sandwiched inside a “J-Town” jam and a cover of The Lion King‘s “I Just Can’t Wait To Be King” that recalled their Disney-themed 2017 New Year’s Eve performance, cleverly dubbed “DisNYE.” The entertaining covers came among fantastic renditions of Pigeons Playing Ping Pong favorites old and new like “Porcupine”, “Walk Outside”, “Henrietta”, “Su Casa”, “Whirled”, “Julia”, “Whoopie”, “Avalanche”, “Landing”, “CWA”, and “Bad For You”. The band finally finished out strong with a marvelous “Horizon” and a set-closing “Ocean Flows” before putting a bow on the performance with a “Dawn A New Day” encore.Below, you can check out a full gallery of photos from Pigeons Playing Ping Pong’s first of two Portland performances below courtesy of photographer Victor Brazen.For a full list of Pigeons Playing Ping Pong’s upcoming tour dates, head to the band’s website.Setlist: Pigeon Playing Ping Pong | Port City Music Hall | Portland, ME | 4/14/18Set 1:PorcupineWalk OutsideJ-Town > Psycho Killer* > J-Town >>Henrietta >>Su Casa >>WhirledJuliaSet 2WhoopieAvalancheLanding > Drums >Just Can’t Wait To Be KingCWA >>Bad For YouHorizonOcean FlowsE. Dawn A New DayNotes:* InvertedSold Out showPigeon Playing Ping Pong | Port City Music Hall | Portlant, ME | 4/14/18 | Photos: Victor Brazen Load remaining images
In one of the largest efforts to build a comprehensive catalog of genetic vulnerabilities in cancer, researchers from the Broad Institute of MIT and Harvard and Dana-Farber Cancer Institute have identified more than 760 genes upon which multiple types of cancer cells are strongly dependent for their growth and survival.Many of these “dependencies,” the researchers report today in the journal Cell, are specific to certain cancer types. However, about 10 percent of them are common across multiple cancers, suggesting that a relatively small number of therapies targeting these core dependencies might each hold promise for combating several tumors.To generate these findings, the research team conducted genome-wide RNA interference (RNAi) screens on 501 cell lines representing more than 20 types of cancer, silencing more than 17,000 genes individually in each line to identify genetic dependencies unique to cancerous cells.Cancer cells can harbor a broad variety of genetic errors, from small mutations to wholesale swaps of DNA between chromosomes. If an error shuts down a critical gene, a cancerous cell will compensate by adjusting other genes’ activity, frequently developing a dependence on such adaptations in order to persist.Graphic: The Broad Institute of MIT and HarvardIdentifying these dependencies provides opportunities for scientists to gain deeper insight into cancer biology and determine new therapeutic targets.“Much of what has been and continues to be done to characterize cancer has been based on genetics and sequencing. That’s given us the parts list,” said study co-senior author William Hahn, an institute member in the Broad Cancer Program, chief of the Division of Molecular and Cellular Oncology at Dana-Farber, and a leader in the Cancer Dependency Map initiative, a joint effort spanning the Broad Institute and Dana-Farber. “Mapping dependencies ascribes function to the parts and shows you how to reverse-engineer the processes that underlie cancer.”RNAi silences genes using small pieces of RNA called small interfering RNAs (siRNAs). To run a genome-wide RNAi screen, researchers expose cells to pools of siRNAs and track the cells’ behavior.“The simplest thing one can do with perturbed cells is allow them to keep growing over time and see which ones thrive,” explained study co-senior author David Root, an institute scientist and director of the Genetic Perturbation Platform at the Broad. “If cells with a certain gene silenced disappear, for example, it means that gene is essential for proliferation.”The data revealed striking patterns in cancer cells’ dependencies. Many dependencies were cancer-specific, in that silencing each affected only a subset of the cell lines. However, more than 90 percent of the cell lines had a strong dependency on at least one of a set of 76 genes, suggesting that many cancers rely on a relatively few genes and pathways.Using a set of molecular features (e.g., mutations, gene copy numbers, expression patterns) from each cell line, the team also generated biomarker-based models that helped explain the biology behind 426 of the 769 dependencies. Most of those biomarkers fell into four broad categories:Mutation(s) of a gene;Loss of a copy or reduced expression of a gene;Increased expression of a gene;Reliance on a gene functionally or structurally related to another, lost gene (a.k.a., a paralog dependence).Surprisingly, more than 80 percent of the dependencies with biomarkers were associated with changes (up or down) in a gene’s expression. Mutations, often used as the grounds for pursuing a gene as a drug target, accounted for merely 16 percent of biomarker-associated dependencies.Twenty percent of the dependencies the team discovered were associated with genes previously identified as potential drug targets.“We can’t say we’ve found everything, but we can say that the genes we’re seeing fall into a relatively small number of bins, some of which are familiar, some less so,” Hahn said. “That initial taxonomy is a great starting point for building a full map.”“Our results provide a starting point for therapeutic projects to decide where to focus their efforts,” said study co-first author Francisca Vazquez, a Cancer Dependency Map project leader. She added that while there was still much to do to validate the list, “It’s becoming increasingly easier to triangulate data and generate hypotheses as more genome-scale systematic data sets, like those from the Cancer Cell Line Encyclopedia, Genotype-Tissue Expression, and the Cancer Genome Atlas projects, become available.“Bringing of all the data together will help us generate a truly comprehensive cancer dependency map.”To eliminate false-positive results caused by seed effects — a phenomenon by which siRNAs inadvertently silence irrelevant genes — study co-first author Aviad Tsherniak led the development of a novel computational tool dubbed DEMETER.“People sometimes take a dim view of RNAi because seed effects make the data so noisy,” said Tsherniak, leader of the Broad Cancer Program’s Data Science group. “DEMETER models gene knockdown and seed effects within the data, and computationally subtracts the seed effects. It cleans up the data and helps you find true dependencies.”According to Hahn, the data argue that the time is ripe to pay more attention to the broader landscape of functional aspects of cancer, in addition to focusing on protein-coding gene mutations and variations.“I think we’re close to the end of finding genes that are mutated or focally amplified in cancer,” he said. “To me, that’s a huge opportunity, because it means we have many heretofore untapped avenues for understanding cancer.”Jesse Boehm, associate director of the Broad Cancer Program, and Todd Golub, director of the Cancer Program and chief scientific officer of the Broad Institute, were also co-senior authors on this study.Complete results from the study are available through a dedicated portal.This work was conducted as part of the Slim Initiative in Genomic Medicine for the Americas (SIGMA), a joint U.S.-Mexico project funded by the Carlos Slim Foundation. SIGMA focuses on several key diseases with particular relevance to public health in Mexico and Latin America, including type 2 diabetes and cancer. Additional funding was provided by the National Cancer Institute.
The man charged in a California kidnapping that police initially dismissed as a hoax said he acted alone, and that mental illness and a side effect from a vaccine contributed to his behavior, the FBI said in a court filing. (Thanawala, 9/2) The Sacramento Bee: Deal On State Retiree Health Care Benefits May Set Precedent If the Ohio Supreme Court upholds a decision that exempted some of a patient’s medical records from his daughters’ request, hospitals could hide critical details about the care of those who are harmed or die there, say the plaintiffs of a case heard this morning. The lawsuit arose in Canton, where Howard E. Griffith died in 2012 at Aultman Hospital. Griffith’s heart monitor somehow was ripped off and he spent 40 minutes alone before he was found unresponsive, according to court records. He died two days later in intensive care. (Crane, 9/2) Los Angeles Times: Stories Of Mexican Mothers Having Babies In U.S. Are Complex, Texas Doctors Say State Highlights: Calif. Deal With Key Unions Advances Idea Of Paying Forward For Retiree Health Benefits; Ohio High Court To Hear Medical Records Case Health care stories are reported from California, Ohio, Georgia, Pennsylvania, New Jersey, Delaware, North Carolina, Minnesota, California and Nebraska. The Columbus Post-Dispatch: Ohio Supreme Court Hears Case About Medical Records And Patient Rights Georgia Health News: Northside, Gwinnett Medical Talk Giant Merger Up until now, Northside Hospital has stayed relatively quiet in the almost frantic rush by metro Atlanta hospital systems to seek mergers or acquisitions. But Northside is now jumping into the fray, with a Wednesday announcement that it and Gwinnett Medical Center will begin talks to merge operations.(Miller, 9/2) While critics have appropriately pushed back citing the high cost, ineffectiveness, and impracticality of mass deportation, there is another consequence that has been largely overlooked, which is the grave impact that kicking millions of people out of the country would have on the health of those directly affected, on their families, on their communities, and on the overall health of our country. There are an estimated 160,000 undocumented persons in Pennsylvania and another 550,000 in New Jersey (2010 estimates) whose health could be directly placed at risk under a mass deportation policy. It is this concern about the health consequences of deportation that led the American College of Physicians, my employer, to urge physicians to speak out, individually and collectively, against mass deportation, reaffirming a position that it first adopted in 2011. ACP, based in Philadelphia, is the nations’ largest physician specialty society and second largest physician membership organization, representing 143,000 internal medicine physician and medical student members. (Doherty, 9/2) The Associated Press: Delaware Business Group Calls For Reining In State Spending The Philadelphia Inquirer: U.S. Internal Medicine Docs: Mass Deportation Would Be Bad For Country’s Health The Associated Press: Nebraska Nursing Home For Native Americans To Open Next Year MPR News: Medical Marijuana Company Delays 2 Clinic Openings The Associated Press: School Drug Counselors Charged In $46M Fraud Scheme Some were students who had tried drugs or alcohol, but didn’t have substance abuse problems. Others were young addicts in need of help. Neither group necessarily fared well under counseling programs run by a Long Beach company for Los Angeles County schools, federal prosecutors said Wednesday. Dabblers were dubbed abusers, and hard-core users didn’t always get the care they needed. (Melley, 9/2) The mother arrived at the hospital last week in need of an emergency caesarean section, saying she had crossed the border to run an errand in town, not so her baby would be born an American citizen. She assured the doctor that she arrived at the hospital just “because [she] was here.” Dr. Rolando Guerrero listened skeptically. “They always have a story,” he said after delivering her 8-pound boy, Dylan. (Hennessy-Fiske, 9/3) A Minnesota medical cannabis manufacturer won’t open its third dispensary site until patient demand catches up with supply. Minnesota Medical Solutions was set to open a Moorhead location this fall, but CEO Kyle Kingsley said it will have to wait until next spring or summer. (Feshir, 9/2) A long-awaited Nebraska nursing home on the border with South Dakota’s Pine Ridge Indian Reservation will begin accepting Native American residents early next year to ease a severe care shortage in one of the nation’s poorest regions, a project official said Wednesday. The facility is under construction on a 600-acre patch of tribal land in Whiteclay, a tiny Nebraska village on the South Dakota border that is known for selling millions of cans of beer each year to residents of the neighboring dry reservation. (Schulte, 9/2) Gov. Jerry Brown’s administration has reached a tentative deal with a key employee union that would require state engineers to contribute toward their retirement health care benefits, likely establishing a template that will be applied to other state employee unions to help reduce a growing financial liability. Under the three-year agreement, which still must be ratified by the union’s members and the Democratic-dominated Legislature, the Professional Engineers in California Government in mid-2017 would have to begin paying one-half of 1 percent of their pre-tax salaries into a fund to chip away at the fiscal millstone. (Cadelago and Ortiz, 9/2) The study said that instead of raising taxes, officials need to reduce spending growth in education, corrections, personnel and welfare, particularly Medicaid. The study also called for removing regulatory and workforce barriers to economic growth. (Chase, 9/2) The Associated Press: FBI: Defendant In California Kidnapping Blamed Vaccine This is part of the KHN Morning Briefing, a summary of health policy coverage from major news organizations. Sign up for an email subscription.