News Analysis: Getting Polio Campaigns Back on Track





How in the world did something as innocuous as the sugary pink polio vaccine turn into a flash point between Islamic militants and Western “crusaders,” flaring into a confrontation so ugly that teenage girls — whose only “offense” is that they are protecting children — are gunned down in the streets?




Nine vaccine workers were killed in Pakistan last week in a terrorist campaign that brought the work of 225,000 vaccinators to a standstill. Suspicion fell immediately on factions of the Pakistani Taliban that have threatened vaccinators in the past, accusing them of being American spies.


Polio eradication officials have promised to regroup and try again. But first they must persuade the killers to stop shooting workers and even guarantee safe passage.


That has been done before, notably in Afghanistan in 2007, when Mullah Muhammad Omar, spiritual head of the Afghan Taliban, signed a letter of protection for vaccination teams. But in Pakistan, the killers may be breakaway groups following no one’s rules.


Vaccination efforts are also under threat in other Muslim regions, although not this violently yet.


In Nigeria, another polio-endemic country, the new Islamic militant group Boko Haram has publicly opposed it, although the only killings that the news media have linked to polio were those of two police officers escorting vaccine workers. Boko Haram has killed police officers on other missions, unrelated to polio vaccinations.


In Mali, extremists took over half of the country in May, declaring an Islamic state. Vaccination is not an issue yet, but Mali had polio cases as recently as mid-2011, and the virus sometimes circulates undetected.


Resistance to polio vaccine springs from a combination of fear, often in marginalized ethnic groups, and brutal historical facts that make that fear seem justified. Unless it is countered, and quickly, the backlash threatens the effort to eradicate polio in the three countries where it remains endemic: Pakistan, Afghanistan and Nigeria.


In 1988, long before donors began delivering mosquito nets, measles shots, AIDS pills, condoms, deworming drugs and other Western medical goods to the world’s most remote villages, Rotary International dedicated itself to wiping out polio, and trained teams to deliver the vaccine.


But remote villages are often ruled by chiefs or warlords who are suspicious not only of Western modernity, but of their own governments.


The Nigerian government is currently dominated by Christian Yorubas. More than a decade ago, when word came from the capital that all children must swallow pink drops to protect them against paralysis, Muslim Hausas in the far-off north could be forgiven for reacting the way the fundamentalist Americans of the John Birch Society did in the 1960s when the government in far-off Washington decreed that, for the sake of children’s teeth, all drinking water should have fluoride.


The northerners already had grievances. In 1996, the drug company Pfizer tested its new antibiotic, Trovan, during a meningitis outbreak there. Eleven children died. Although Pfizer still says it was not to blame, the trial had irregularities, and last year the company began making payments to victims.


Other rumors also spring from real events.


In Pakistan, resistance to vaccination, low over all, is concentrated in Pashtun territory along the Afghan border and in Pashtun slums in large cities. Pashtuns are the dominant tribe in Afghanistan but a minority in Pakistan among Punjabis, Sindhis, Baluchis and other ethnic groups. Many are Afghan refugees and are often poor and dismissed as medieval and lawless.


Pakistan’s government is friendly with the United States while the Pashtuns’ territory in border areas has been heavily hit by American Taliban-hunting drones, which sometimes kill whole families.


So, when the Central Intelligence Agency admitted sponsoring a hepatitis vaccination campaign as a ruse to get into a compound in Pakistan to confirm that Osama bin Laden was there, and the White House said it had contemplated wiping out the residence with a drone missile, it was not far-fetched for Taliban leaders to assume that other vaccinators worked for the drone pilots.


Even in friendly areas, the vaccine teams have protocols that look plenty suspicious. If a stranger knocked on a door in Brooklyn, asked how many children under age 5 were at home, offered to medicate them, and then scribbled in chalk on the door how many had accepted and how many refused — well, a parent might worry.


In modern medical surveys — though not necessarily on polio campaigns — teams carry GPS devices so they can find houses again. Drones use GPS coordinates.


The warlords of Waziristan made the connection specific, barring all vaccination there until Predator drones disappeared from the skies.


Dr. Bruce Aylward, a Canadian who is chief of polio eradication for the World Health Organization, expressed his frustration at the time, saying, “They know we don’t have any control over drone strikes.”


The campaign went on elsewhere in Pakistan — until last week.


The fight against polio has been hampered by rumors that the vaccine contains pork or the virus that causes AIDS, or is a plot to sterilize Muslim girls. Even the craziest-sounding rumors have roots in reality.


The AIDS rumor is a direct descendant of Edward Hooper’s 1999 book, “The River,” which posited the theory — since discredited — that H.I.V. emerged when an early polio vaccine supposedly grown in chimpanzee kidney cells contaminated with the simian immunodeficiency virus was tested in the Belgian Congo.


The sterilization claim was allegedly first made on a Nigerian radio station by a Muslim doctor upset that he had been passed over for a government job. The “proof” was supposed to be lab tests showing it contained estrogen, a birth control hormone.


The vaccine virus is grown in a broth of live cells; fetal calf cells are typical. They may be treated with a minute amount of a digestive enzyme, trypsin — one source of which is pig pancreas, which could account for the pork rumor.


In theory, a polio eradicator explained, if a good enough lab tested the vaccine used at the time the rumor started, it might have detected estrogen from the calf’s mother, but it would have been far less estrogen than is in mother’s milk, which is not accused of sterilizing anyone. The trypsin is supposed to be washed out.


In any case, polio vaccine is now bought only from Muslim countries like Indonesia, and Muslim scholars have ruled it halal — the Islamic equivalent of kosher.


Reviving the campaign will mean quelling many rumors. It may also require adding other medical “inducements,” like deworming medicine, mosquito nets or vitamin A, whose immediate benefits are usually more obvious.


But changing mind-sets will be a crucial step, said Dr. Aylward, who likened the shootings of the girls to those of the schoolchildren in Newtown, Conn.


More police involvement — what he called a “bunkerized approach” — would not solve either America’s problem or Pakistan’s, he argued. Instead, average citizens in both countries needed to rise up, reject the twisted thinking of the killers and “generate an understanding in the community that this kind of behavior is not acceptable.”


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West Antarctic Warming Faster Than Thought, Study Finds





West Antarctica has warmed much more than scientists had thought over the last half century, new research suggests, an ominous finding given that the huge ice sheet there may be vulnerable to long-term collapse, with potentially drastic effects on sea levels.




A paper released on Sunday by the journal Nature Geoscience reports that the temperature at a research station in the middle of West Antarctica has warmed by 4.4 degrees Fahrenheit since 1958. That is roughly twice as much as scientists previously thought and three times the overall rate of global warming, making central West Antarctica one of the fastest-warming regions on earth.


“The surprises keep coming,” said Andrew J. Monaghan, a scientist at the National Center for Atmospheric Research in Boulder, Colo., who took part in the study. “When you see this type of warming, I think it’s alarming.”Of course, warming in Antarctica is a relative concept. West Antarctica remains an exceedingly cold place, with average annual temperatures in the center of the ice sheet that are nearly 50 degrees Fahrenheit below freezing.


But the temperature there does sometimes rise above freezing in the summer, and the new research raises the possibility that it might begin to happen more often, potentially weakening the ice sheet through surface melting. The ice sheet is already under attack at the edges by warmer ocean water, and scientists are on alert for any fresh threat.


A potential collapse of the West Antarctic ice sheet is one of the long-term hazards that have led experts to worry about global warming. The base of the ice sheet sits below sea level, in a configuration that makes it especially vulnerable. Scientists say a breakup of the ice sheet, over a period that would presumably last at least several hundred years, could raise global sea levels by 10 feet, possibly more.


The new research is an attempt to resolve a scientific controversy that erupted several years ago about exactly how fast West Antarctica is warming. With few automated weather stations and even fewer human observers in the region, scientists have had to use statistical techniques to infer long-term climate trends from sparse data.


A nearby area called the Antarctic Peninsula, which juts north from West Antarctica and for which fairly good records are available, was already known to be warming rapidly. A 2009 paper found extensive warming in the main part of West Antarctica, but those results were challenged by a group that included climate change contrarians.


To try to get to the bottom of the question, David H. Bromwich of Ohio State University pulled together a team that focused on a single temperature record. At a lonely outpost called Byrd Station, in central West Antarctica, people and automated equipment have been keeping track of temperature and other weather variables since the late 1950s.


It is by far the longest weather record in that region, but it had intermittent gaps and other problems that had made many researchers wary of it. The Bromwich group decided to try to salvage the Byrd record.


They retrieved one of the sensors and recalibrated at the University of Wisconsin. They discovered a software error that had introduced mistakes into the record and then used computerized analyses of the atmosphere to fill the gaps.


The reconstruction will most likely undergo intensive scientific scrutiny, which Dr. Bromwich said he would welcome. “We’ve tested everything we could think of,” he said.


Assuming the research holds up, it suggests that the 2009 paper, far from overestimating warming in West Antarctica, had probably underestimated it, especially in summer.


Eric J. Steig, a University of Washington researcher who led the 2009 work, said in an interview that he considered his paper to have been supplanted by the new research. “I think their results are better than ours, and should be adopted as the best estimate,” he said. He noted that the new Byrd record matches a recent temperature reconstruction from a nearby borehole in the ice sheet, adding confidence in the findings.


Much of the warming discovered in the new paper happened in the 1980s, around the same time the planet was beginning to warm briskly. More recently, Dr. Bromwich said, the weather in West Antarctica seems to have become somewhat erratic. In the summer of 2005, the interior of West Antarctica warmed enough for the ice to undergo several days of surface melting.


Dr. Bromwich is worried that this could eventually become routine, perhaps accelerating the decay of the West Antarctic ice sheet, but the warming is not fast enough for that to happen right away. “We’re talking decades into the future, I think,” Dr. Bromwich said.


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Colts, Bengals make playoffs with wins


One year after putting together the NFL's worst record, the Indianapolis Colts are headed to the playoffs.


Joining them on Sunday were the Cincinnati Bengals.


The Colts (10-5) equaled the 2008 Miami Dolphins as the only teams to win at least 10 games after losing 14 or more the previous season. Top overall draft pick Andrew Luck completed a 7-yard touchdown pass to Reggie Wayne late in the fourth quarter for a 20-13 victory at Kansas City.


Cincinnati qualified for a second straight postseason berth for only the second time in franchise history, edging archrival Pittsburgh 13-10. The Bengals have never gone to the playoffs in successive years that did not involve a strike-shortened season.


Luck finished with 205 yards passing to break Cam Newton's year-old rookie record of 4,051 yards in a season. He also extended his rookie record for fourth-quarter comebacks to seven by leading his team downfield in the closing minutes.


"Mission accomplished. That's all I can say," Colts interim coach Bruce Arians said. "Without getting emotional again, knowing that (coach Chuck Pagano) is going to be back Monday, the work week shouldn't be as stressful."


For the Bengals (9-6), Andy Dalton hit A.J. Green with a 21-yard pass in the final moments, setting up Josh Brown's 43-yard field goal with 4 seconds remaining. The loss eliminated the Steelers from contention.


Minnesota's 23-6 win at Houston prevented the Texans from earning home-field advantage throughout the AFC playoffs. AFC South champion Houston (12-3) still can get that by winning at Indianapolis in the season finale.


Washington's 27-20 win at Philadelphia, combined with New Orleans beating Dallas 34-31 in overtime means the Redskins will win the NFC East by beat the Cowboys next week.


Green Bay clinched at least the third seed in the NFC when it routed Tennessee 55-7. The NFC North champs (11-4) still could wind up second overall in the conference and get a bye.


On Saturday night, NFC South winner Atlanta won 31-18 at Detroit to clinch home-field advantage throughout the conference playoffs.


___


Online: http://pro32.ap.org/poll and http://twitter.com/AP_NFL


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Genetic Gamble : Drugs Aim to Make Several Types of Cancer Self-Destruct


C.J. Gunther for The New York Times


Dr. Donald Bergstrom is a cancer specialist at Sanofi, one of three companies working on a drug to restore a tendency of damaged cells to self-destruct.







For the first time ever, three pharmaceutical companies are poised to test whether new drugs can work against a wide range of cancers independently of where they originated — breast, prostate, liver, lung. The drugs go after an aberration involving a cancer gene fundamental to tumor growth. Many scientists see this as the beginning of a new genetic age in cancer research.




Great uncertainties remain, but such drugs could mean new treatments for rare, neglected cancers, as well as common ones. Merck, Roche and Sanofi are racing to develop their own versions of a drug they hope will restore a mechanism that normally makes badly damaged cells self-destruct and could potentially be used against half of all cancers.


No pharmaceutical company has ever conducted a major clinical trial of a drug in patients who have many different kinds of cancer, researchers and federal regulators say. “This is a taste of the future in cancer drug development,” said Dr. Otis Webb Brawley, the chief medical and scientific officer of the American Cancer Society. “I expect the organ from which the cancer came from will be less important in the future and the molecular target more important,” he added.


And this has major implications for cancer philanthropy, experts say. Advocacy groups should shift from fund-raising for particular cancers to pushing for research aimed at many kinds of cancer at once, Dr. Brawley said. John Walter, the chief executive officer of the Leukemia and Lymphoma Society, concurred, saying that by pooling forces “our strength can be leveraged.”


At the heart of this search for new cancer drugs are patients like Joe Bellino, who was a post office clerk until his cancer made him too sick to work. Seven years ago, he went into the hospital for hernia surgery, only to learn he had liposarcoma, a rare cancer of fat cells. A large tumor was wrapped around a cord that connects the testicle to the abdomen. “I was shocked,” he said in an interview this summer.


Companies have long ignored liposarcoma, seeing no market for drugs to treat a cancer that strikes so few. But it is ideal for testing Sanofi’s drug because the tumors nearly always have the exact genetic problem the drug was meant to attack — a fusion of two large proteins. If the drug works, it should bring these raging cancers to a halt. Then Sanofi would test the drug on a broad range of cancers with a similar genetic alteration. But if the drug fails against liposarcoma, Sanofi will reluctantly admit defeat.


“For us, this is a go/no-go situation,” said Laurent Debussche, a Sanofi scientist who leads the company’s research on the drug.


The genetic alteration the drug targets has tantalized researchers for decades. Normal healthy cells have a mechanism that tells them to die if their DNA is too badly damaged to repair. Cancer cells have grotesquely damaged DNA, so ordinarily they would self-destruct. A protein known as p53 that Dr. Gary Gilliland of Merck calls the cell’s angel of death normally sets things in motion. But cancer cells disable p53, either directly, with a mutation, or indirectly, by attaching the p53 protein to another cellular protein that blocks it. The dream of cancer researchers has long been to reanimate p53 in cancer cells so they will die on their own.


The p53 story began in earnest about 20 years ago. Excitement ran so high that, in 1993, Science magazine anointed it Molecule of the Year and put it on the cover. An editorial held out the possibility of “a cure of a terrible killer in the not too distant future.”


Companies began chasing a drug to restore p53 in cells where it was disabled by mutations. But while scientists know how to block genes, they have not figured out how to add or restore them. Researchers tried gene therapy, adding good copies of the p53 gene to cancer cells. That did not work.


Then, instead of going after mutated p53 genes, they went after half of cancers that used the alternative route to disable p53, blocking it by attaching it to a protein known as MDM2. When the two proteins stick together, the p53 protein no longer functions. Maybe, researchers thought, they could find a molecule to wedge itself between the two proteins and pry them apart.


The problem was that both proteins are huge and cling tightly to each other. Drug molecules are typically tiny. How could they find one that could separate these two bruisers, like a referee at a boxing match?


In 1996, researchers at Roche noticed a small pocket between the behemoths where a tiny molecule might slip in and pry them apart. It took six years, but Roche found such a molecule and named it Nutlin because the lab was in Nutley, N.J.


But Nutlins did not work as drugs because they were not absorbed into the body.


Roche, Merck and Sanofi persevered, testing thousands of molecules.


At Sanofi, the stubborn scientist leading the way, Dr. Debussche, maintained an obsession with p53 for two decades. Finally, in 2009, his team, together with Shaomeng Wang at the University of Michigan and a biotech company, Ascenta Therapeutics, found a promising compound.


The company tested the drug by pumping it each day into the stomachs of mice with sarcoma.


Read More..

Boston Priest to Lead Vatican’s Oversight of Sexual Abuse Claims





Pope Benedict XVI on Saturday appointed as the Vatican’s new sexual crimes prosecutor a priest who handled clergy sexual abuse cases in the Roman Catholic Church in Boston at the height of the scandal and for years afterward.




The pope also pardoned his former butler, who was serving a prison term after leaking confidential documents in the Vatican’s most embarrassing security breach in decades.


The Vatican said the new prosecutor, the Rev. Robert W. Oliver, the top canon lawyer at the Archdiocese of Boston under Cardinal Sean P. O’Malley, would be the “promoter of justice” at the Congregation for the Doctrine of the Faith, the Vatican’s doctrinal office that reviews all abuse cases.


In a statement released by the Archdiocese of Boston, Father Oliver said, “It is with deep humility and gratitude that I received the news that the Holy Father is entrusting me with this service to the church.”


Father Oliver was among the canon lawyers brought in to advise Cardinal Bernard F. Law on sexual abuse cases in Boston, where the church’s abuse scandal erupted anew in 2002. He was put in charge of the office investigating charges against accused priests after the cardinal was forced to resign in 2002 amid an uproar over revelations that he had kept abusive priests working in parishes.


Father Oliver helped write the archdiocese’s new abuse prevention policy in 2003. He has been serving as the top canon lawyer for the archdiocese and as a visiting professor of canon law at Catholic University of America in Washington.


Advocates for abuse victims in the Boston archdiocese criticized his record on Saturday. Anne Barrett Doyle, co-director of Bishop Accountability, a watchdog group that maintains an archive of abuse cases and documents, said in an interview, “Reverend Oliver is a champion of accused priests, which obviously does not bode well for the job he will do as promoter of justice.”


She said that under that under Father Oliver’s guidance, the Boston archdiocese reported that between 2003 and 2005 it had cleared 32 of 71 accused priests, about 45 percent, saying it did not find “probable cause” to pursue abuse cases against them. That was a far higher clearance rate than the 10 percent reported by other dioceses nationwide, according to a report in 2005 by the United States Conference of Catholic Bishops.


She also said the new policy on abuse that Father Oliver helped write in 2003 allows accused priests to remain in the ministry without being publicly identified while allegations against them are investigated. In contrast, laypeople suspected of abuse who work or volunteer for the church are to be immediately suspended.


Father Oliver is not expected to grant any interviews, said Terrence C. Donilon, a secretary for communications for the Archdiocese of Boston. But, he said, “any attacks on Father Oliver’s distinguished track record of service to the church and his many contributions to the response to clergy sexual abuse are unfounded and just plain wrong.”


As for the archdiocese’s policy and record, Mr. Donilon also said, “We do not have any priests in active ministry who have been credibly accused of child abuse.” He added that the archdiocese immediately turns over all allegations to civil authorities and has put in place many measures to prevent abuse.


Father Oliver succeeds Msgr. Charles Scicluna, 53, who was promoted to auxiliary bishop in his native Malta in October. A friendly canon lawyer, Monsignor Scicluna found himself in the eye of the storm after being named promoter of justice in 2002.


The year before, Pope John Paul II decreed that all abuse cases be sent directly to the doctrinal office, then led by Cardinal Joseph Ratzinger, now Pope Benedict.


When the scandal erupted in Europe in 2010, with cases emerging in Ireland and the pope’s native Germany — including some that called into question how Benedict handled an abuse case when he was archbishop of Munich in 1980 — the Vatican issued new guidelines, essentially telling bishops to report abuse cases to the police where local laws required it.


The Vatican also said Saturday that Benedict had pardoned his former butler, Paolo Gabriele, 46, who had been sentenced to prison after admitting to leaking confidential documents that formed the basis of a tell-all book on alleged misdeeds, financial mismanagement, back-stabbing and infighting within the Vatican.


On Saturday, Benedict met with Mr. Gabriele in the Vatican police barracks and set him free, said the Vatican spokesman, the Rev. Federico Lombardi.


Laurie Goodstein reported from New York, and Rachel Donadio from Rome.



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Facebook releases ‘Poke’ for the iPhone to compete with Snapchat









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La.-Lafayette tops ECU in New Orleans Bowl, 43-34


NEW ORLEANS (AP) — Whether Terrance Broadway was throwing, running, or throwing on the run, he gave East Carolina fits and justified Louisiana-Lafayette coach Mark Hudspeth's decision to let his sophomore quarterback finish the season as his starter.


Broadway passed for 316 yards and ran for 108, helping Louisiana-Lafayette repeat as winners of the New Orleans Bowl with a 43-34 victory against East Carolina on Saturday.


The performance capped a 2012 campaign which opened with Broadway backing up senior Blaine Gautier, who broke a bone in his throwing hand in late September.


"Terrance comes in and just has a phenomenal season," Hudspeth said, describing the difficult decision not to give Gautier, the New Orleans Bowl MVP a year ago, his job back when he was healthy again late in the season. "We really had hit our stride and the best thing about Blaine is he understood."


Broadway had to sit out last season after transferring from Houston, and saw this year's New Orleans Bowl as his first real chance to add some kind of championship to his name after coming up short as a high school standout in Baton Rouge, La.


"My main goal was to get our team a big win in this bowl game and just to get that monkey off my back that I didn't have a ring from high school and last year," Broadway said. "I was very focused on that."


Alonzo Harris rushed for 120 yards, including touchdowns of 6 and 68 yards for the Ragin' Cajuns (9-4), who briefly squandered a three-touchdown lead before moving back in front for good on Broadway's 14-yard scoring pass to Javone Lawson late in the third quarter.


"Nothing fazes our team," said Broadway, who also ran for a 12-yard score. "Everybody on our team responds to adversity well. So when they came back on us and made a game out of it, our team is still upbeat and saying we're going to win this game."


And they did, with Brett Baer adding his second and third field goals in the fourth quarter to seal the victory.


Shane Carden passed for 278 yards and two touchdowns for East Carolina (8-5) but was intercepted in Cajuns territory by Jemarlous Moten in the fourth quarter as ECU drove for a potential tying or go-ahead score.


"They did a good job of changing, I guess, the coverage throughout the game," Carden said of ULL. "But I think our offense could execute a lot better. It was nothing really they were doing. It was a lot of us just not executing routine plays."


The Pirates' Reggie Bullock rushed for 104 yards and two touchdowns.


"The game plan was fine. We just needed the execution of the calls. We've always played hard. That was not a problem," East Carolina coach Ruffin McNeill said. "We had a chance there late in the game. ... I was proud of our guys."


Carden's touchdowns went to Justin Hardy for 19 yards and Danny Webster for 16 yards. Hardy finished with five catches for 59 yards. East Carolina's Andrew Bodenheimer had five catches for a team-high 65 yards, but could not secure a crucial fourth-down pass in the final minutes as defensive back T.J. Worthy ripped the ball away in ECU territory. That allowed the Cajuns to run the clock down to 15 seconds before setting up Baer's final field goal from 40-yards out.


Jamal Robinson had six catches for 116 yards for ULL, including a 39-yarder that was Broadway's longest completion. Lawson finished with four catches for 71 yards.


The Cajuns carried a 37-31 lead into the fourth quarter after Lawson juggled but secured the ball for a sprawling, rolling TD catch. The point-after kick failed, however, and East Carolina made it 37-34 on Warren Harvey's 26-yard field goal.


Broadway's interception on a tipped pass gave East Carolina the ball on the Cajuns 39, but Moten stepped in front of Carden's long pass over the middle to help preserve the slim lead.


Red-clad Ragin' Cajuns fans made up the bulk of a record New Orleans Bowl crowd of 48,828, and they were celebrating early.


Broadway's scoring run, his ninth rushing TD of the season, gave ULL a 7-0 lead and Harry Peoples' 10-yard scoring made it 14-0.


ECU didn't get a first down until early in the second quarter, when Carden converted on third-and-long with Jabril Solomon for a 45-yard gain. That set up Bullock's first touchdown from 5 yards out to make it 14-7.


Harris' two scores had the Cajuns seemingly in command at 28-7, but ECU responded with two touchdowns in a span of 13 seconds to make it a one-score game.


First came Hardy's leaping, outstretched grab in the back of the end zone. Then Darryl Surgent fumbled a kickoff return, giving ECU the ball on the Cajuns 16. Carden found Webster over the middle for a score on the next play.


Louisiana-Lafayette was able to regain some momentum in the final 37 seconds of the first half, driving 47 yards on five plays to set up Baer's 50-yard field goal, which was the same distance and direction as his game-winner at the end of last year's New Orleans Bowl.


The Pirates tied it in the third quarter on Harvey's 45-yard field goal and Bullock's 13-yard scoring run, capping a drive that included a converted fourth-and-3.


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Genetic Gamble : Drugs Aim to Make Several Types of Cancer Self-Destruct


C.J. Gunther for The New York Times


Dr. Donald Bergstrom is a cancer specialist at Sanofi, one of three companies working on a drug to restore a tendency of damaged cells to self-destruct.







For the first time ever, three pharmaceutical companies are poised to test whether new drugs can work against a wide range of cancers independently of where they originated — breast, prostate, liver, lung. The drugs go after an aberration involving a cancer gene fundamental to tumor growth. Many scientists see this as the beginning of a new genetic age in cancer research.




Great uncertainties remain, but such drugs could mean new treatments for rare, neglected cancers, as well as common ones. Merck, Roche and Sanofi are racing to develop their own versions of a drug they hope will restore a mechanism that normally makes badly damaged cells self-destruct and could potentially be used against half of all cancers.


No pharmaceutical company has ever conducted a major clinical trial of a drug in patients who have many different kinds of cancer, researchers and federal regulators say. “This is a taste of the future in cancer drug development,” said Dr. Otis Webb Brawley, the chief medical and scientific officer of the American Cancer Society. “I expect the organ from which the cancer came from will be less important in the future and the molecular target more important,” he added.


And this has major implications for cancer philanthropy, experts say. Advocacy groups should shift from fund-raising for particular cancers to pushing for research aimed at many kinds of cancer at once, Dr. Brawley said. John Walter, the chief executive officer of the Leukemia and Lymphoma Society, concurred, saying that by pooling forces “our strength can be leveraged.”


At the heart of this search for new cancer drugs are patients like Joe Bellino, who was a post office clerk until his cancer made him too sick to work. Seven years ago, he went into the hospital for hernia surgery, only to learn he had liposarcoma, a rare cancer of fat cells. A large tumor was wrapped around a cord that connects the testicle to the abdomen. “I was shocked,” he said in an interview this summer.


Companies have long ignored liposarcoma, seeing no market for drugs to treat a cancer that strikes so few. But it is ideal for testing Sanofi’s drug because the tumors nearly always have the exact genetic problem the drug was meant to attack — a fusion of two large proteins. If the drug works, it should bring these raging cancers to a halt. Then Sanofi would test the drug on a broad range of cancers with a similar genetic alteration. But if the drug fails against liposarcoma, Sanofi will reluctantly admit defeat.


“For us, this is a go/no-go situation,” said Laurent Debussche, a Sanofi scientist who leads the company’s research on the drug.


The genetic alteration the drug targets has tantalized researchers for decades. Normal healthy cells have a mechanism that tells them to die if their DNA is too badly damaged to repair. Cancer cells have grotesquely damaged DNA, so ordinarily they would self-destruct. A protein known as p53 that Dr. Gary Gilliland of Merck calls the cell’s angel of death normally sets things in motion. But cancer cells disable p53, either directly, with a mutation, or indirectly, by attaching the p53 protein to another cellular protein that blocks it. The dream of cancer researchers has long been to reanimate p53 in cancer cells so they will die on their own.


The p53 story began in earnest about 20 years ago. Excitement ran so high that, in 1993, Science magazine anointed it Molecule of the Year and put it on the cover. An editorial held out the possibility of “a cure of a terrible killer in the not too distant future.”


Companies began chasing a drug to restore p53 in cells where it was disabled by mutations. But while scientists know how to block genes, they have not figured out how to add or restore them. Researchers tried gene therapy, adding good copies of the p53 gene to cancer cells. That did not work.


Then, instead of going after mutated p53 genes, they went after half of cancers that used the alternative route to disable p53, blocking it by attaching it to a protein known as MDM2. When the two proteins stick together, the p53 protein no longer functions. Maybe, researchers thought, they could find a molecule to wedge itself between the two proteins and pry them apart.


The problem was that both proteins are huge and cling tightly to each other. Drug molecules are typically tiny. How could they find one that could separate these two bruisers, like a referee at a boxing match?


In 1996, researchers at Roche noticed a small pocket between the behemoths where a tiny molecule might slip in and pry them apart. It took six years, but Roche found such a molecule and named it Nutlin because the lab was in Nutley, N.J.


But Nutlins did not work as drugs because they were not absorbed into the body.


Roche, Merck and Sanofi persevered, testing thousands of molecules.


At Sanofi, the stubborn scientist leading the way, Dr. Debussche, maintained an obsession with p53 for two decades. Finally, in 2009, his team, together with Shaomeng Wang at the University of Michigan and a biotech company, Ascenta Therapeutics, found a promising compound.


The company tested the drug by pumping it each day into the stomachs of mice with sarcoma.


Read More..

The Lede Blog: Bahrain Welcomes European Delegation, Not Delegates' Calls to Free Dissidents

As The Lede reported on Wednesday, a delegation from the European Parliament visited Bahrain this week to discuss human rights, just as the kingdom jailed a rights advocate for documenting a protest on Twitter.

Bahrain’s state media presented the visit as evidence that the kingdom is committed to human rights — one report showed the delegates meeting with the head of an official human rights organization established by royal decree, another their briefing by the royal who oversees the police force “on human rights reforms that have been implemented within the interior ministry.”

What the country’s official news agency did not report, however, is that the head of the delegation, Inese Vaidere of Latvia, called for the release of all “prisoners of conscience” currently being detained for their role in the protest movement.

Ms. Vaidere’s call was joined by at least two other members of the delegation, Richard Howitt of Britain and Ana Gomes of Portugal, who issued a joint statement calling on the government to immediately release up to 800 “political prisoners” and begin direct talks with the opposition.

Ms. Gomes was barred from entering Bahrain at the airport when she attempted to visit the kingdom in April to meet with rights activists.

Throughout the three-day visit, Mr. Howitt posted a stream of updates on the delegation’s meetings with Bahraini officials and detained opposition members on his Twitter feed. He said that he questioned the treatment of human rights activists like Said Yousif al-Muhafda, who was jailed on Monday for tweeting about a protest.

Mr. Howitt also described meetings with detained rights activists, including Nabeel Rajab, the president of the Bahrain Center for Human Rights — who was jailed for “inciting” antigovernment protests in speeches and Twitter updates — and the same rights group’s founder, Abdulhadi al-Khawaja — who was sentenced to life in prison by a military court last year for his role in the 2011 protests. Claims that the men are confined in luxurious surroundings are untrue, he reported.

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TSX ends flat as RIM buckles, gold miners bounce






TORONTO (Reuters) – Canada‘s main stock index ended little changed on Friday as gold miners gained on safe-haven buying amid U.S. budget uncertainty, while BlackBerry maker Research In Motion Ltd plunged more than 20 percent.


The index’s materials sector, which includes miners, rose 0.4 percent. Even though the price of gold was near its lowest level in four months, the gold-mining sub-sector added 0.9 percent as investors fretted over stalled U.S. budget talks that could throw Canada’s largest trading partner back into recession.






“As our tiptoes are over the (U.S.) fiscal cliff and we’re looking over the abyss, the markets are upset obviously, and this is sort of putting a damper on the stocks,” said John Ing, president of Maison Placements Canada.


“But we’ve had a mixed reaction in Canada, mainly because the resources have been much better, like gold for example, which is hedging into the uncertainty (around the budget talks),” he said, noting gold miners had been under pressure for the last two weeks.


Miner Barrick Gold Corp edged up 0.2 percent to C$ 33.29. Centerra Gold Inc jumped more than 3 percent to C$ 9.10.


Gold miners are playing catch-up after underperforming throughout the year and could rise further in 2013, said Gavin Graham, president at Graham Investment Strategy.


Shares of RIM dropped 22.2 percent to C$ 10.86 on fears that a new fee structure for its high-margin services segment could put pressure on the business that has set the company apart from its competitors.


The Toronto Stock Exchange‘s S&P/TSX composite index <.gsptse> fell 3.01 points, or 0.02 percent, to end at 12,385.70. It gained 0.7 percent for the week.</.gsptse>


Efforts to avoid the looming U.S. “fiscal cliff” were thrown into disarray on Friday with finger-pointing lawmakers fleeing Washington for Christmas vacations even as the year-end deadline for action edged ever closer.


Graham said that until a deal is reached in the U.S. budget talks, investors will avoid economically sensitive Canadian stocks and those most closely tied to the U.S. economy: auto parts manufacturers, forestry companies and resource stocks generally.


“The resource sectors in Canada, which is half of the index, is going to be adversely affected, correctly or not,” he said.


“Chinese demand is likely to pick up somewhat now with the new leadership there but people will be focused on the U.S. given that it is still by far the most important export market for Canada.”


($ 1=$ 0.99 Canadian)


(Additional reporting by Claire Sibonney, Julie Gordon and Jeffrey Hodgson; Editing by Peter Galloway)


Gadgets News Headlines – Yahoo! News





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