Antibiotics in infancy may cause obesity in adults :

Antibiotics given to infants may have life-long consequences, a study of mice suggests.

Low doses of antibiotics given to pregnant mice and to their newborns led baby mice to become obese as adults,researchers report August 14 in Cell. The effect was not due to the drugs themselves but to the disruption of the rodents’ gut microbiome, the community of microbes living in the mice’s intestines.
“We’re using antibiotics as if there were no cost,” says microbiologist Martin Blaser of New York University, who led the study. “The costs are not immediate but may be long-term.”

Evidence-based medicine actually isn’t :

In medical practice, the concept of evidence shares a lot with Saint Augustine’s understanding of time.

He understood time perfectly well, of course, until somebody asked him to explain it. Medical evidence is similar. Everybody thinks they know what evidencemeans, but defining what counts as evidence is about as easy as negotiating peace in the Middle East. As a result, demands for “evidence-based medicine” pose some serious practical problems. In fact, the label “evidence based” applied to medicine has been confused, abused and misused so much lately that some experts suggest that the evidence-based medicine movement is in a state of crisis.

As evidence for that sweeping generalization, I cite a recent paper by Trisha Greenhalgh (a physician and health care professor) and collaborators, titled “Evidence-based medicine: a movement in crisis?” The question mark notwithstanding, Greenhalgh and colleagues document several aspects of evidence-based medicine that clearly illustrate critical problems with its implementation.

For one thing, the “evidence based” brand has been coopted by special interests (such as companies that make medicines) to further their commercial interests. Companies often define both the disease and its evidence-based treatment:female sexual arousal disorder (treat with sildenafil); male baldness (treat with finasteride); low bone density (treat with alendronate). It’s almost like what counts as a disease (or a disease “risk factor”) depends on whether there is evidence for a drug to “treat” it.

“Evidence-based medicine has drifted in recent years from investigating and managing established disease to detecting and intervening in non-diseases,” Greenhalgh and colleagues wrote in BMJ in June.

Furthermore, the “evidence” favoring various treatments typically comes from trials in which companies decide which drugs to test, at what doses, on how many people. Often the experimental statistical “evidence” in such studies establishes a benefit for a drug that is of little practical value; the supposed benefit, while perhaps real in a mathematical sense, is so slight as to be meaningless for real patients. In other cases, perfectly sound evidence regarding a particular disease is rendered irrelevant in patients afflicted with more than one disorder (patients who are commonly seen in medical practice, but typically excluded from the trials that produced the evidence).

On top of all that, Greenhalgh and colleagues point out, the sheer volume of medical evidence makes assessing it all intelligently essentially impossible. Even the guidelines summarizing the evidence are too voluminous to be useful to doctors.

“The number of [evidence based] clinical guidelines is now both unmanageable and unfathomable,” Greenhalgh and coauthors note. In one 24-hour period in 2005, for instance, a hospital in the United Kingdom admitted 18 patients with 44 diagnoses. The relevant U.K. national guidelines for those patients totaled 3,679 pages. Estimated reading time: 122 hours.

Of course, Greenhalgh and colleagues aren’t arguing against the need for evidence. Rather they are saying the evidence needs to be better, better explained, and more useful to practicing physicians. For one thing, evidence-based medicine should focus more on individual patients, taking their personal differences and needs into account. Evidence-based guidelines should allow for expert judgment to be applied to specific cases, not just blind adherence to algorithmic rules based on statistical averages.

Progress in this regard will require higher publishing standards in medical journals. “Journals editors … should raise the bar for authors to improve the usability of evidence, and especially to require that research findings are presented in a way that informs individualized conversations,” Greenhalgh and collaborators insist.

One further (and particularly pernicious) publication problem involves the evidence that doesn’t get published at all. It might seem like evidence to say that two published studies show that a drug works. But that evidence wouldn’t be so compelling if you knew that three unpublished studies found the drug to be worthless.

Sadly, there is no doubt that much medical research does in fact go unpublished — or perhaps is inappropriately altered or selectively presented in some way to make it publishable. Greenhalgh and colleagues cite one report finding that of 38 studies finding a positive outcome for antidepressants, 37 were published. Of 36 studies with negative results, only 14 were published.

Many other studies have reported evidence that papers with positive (or statistically significant) findings are more likely to get published. One 2008 study, for instance, analyzed 16 papers investigating publication bias in randomized clinical trials and found clear indications of selective publication. Not only were some negative trial results never published, but also even in published papers some non-statistically significant findings were omitted. As a result, the “evidence” in published papers is often skewed, favoring positive results.

“There is strong evidence of an association between significant results and publication,” Kerry Dwan and collaborators wrote in PLOS ONE. “Studies that report positive or significant results are more likely to be published and outcomes that are statistically significant have higher odds of being fully reported.”

In any event, these biases are mere symptoms of the many lamentable maladies afflicting medical evidence in the published literature. Much of the evidence that evidence-based medicine assumes is baloney, based on malfeasance, misunderstandings and faulty methodology. Apparently what we need is evidence-based evidence.

Experimental drugs and vaccines poised to take on Ebola :

As the Ebola virus outbreak continues to run amok in West Africa, scientists are looking ahead to the possibly pivotal use of experimental drugs and vaccines against the disease. It will take months to test, produce and deploy the therapies. But researchers hold out hope that these products — even incompletely vetted — might help to turn the tide against an illness that has defied public health efforts to bring it under control.

The treatments’ use could engender enough hope to encourage people with symptoms — and their close contacts — to come to hospitals, which researchers say would limit the spread of the lethal virus. Having experimental drugs and especially vaccines in hand could also help in recruiting and maintaining adequate levels of hospital staff, who are at high risk of catching the virus.

Using still-experimental drugs has downsides: Even if the treatments help some patients, it will be hard to determine their true effectiveness.  And failed treatments could exacerbate the despair and distrust already hampering public health efforts.

Still, public health officials and bioethics experts say the situation in West Africa is dire enough to warrant putting candidate therapies into use after minimal human safety testing. As of August 19, more than 2,200 people have been infected and more than 1,200 have died, the World Health Organization reports. Earlier this month, WHO declared the outbreak an international public health emergency that is not under control.

The outbreak has hit a thickly populated part of West Africa and spread among the contiguous countries Liberia, Guinea and Sierra Leone. None have encountered Ebola before, and the region has been racked by poverty, civil wars, corrupt government and upheaval. All of the countries have deficient health systems that have suffered even more during the outbreak as some workers abandon their posts.

Health care workers coming into contact with Ebola patients must wear full biohazard gear.

BENJAMIN PARK/CDC

Daniel Bausch, an infectious disease physician at Tulane University in New Orleans, relates an incident in Kenema, Sierra Leone. Dressed in biohazard gear, he and a WHO doctor entered the hospital there in July and were stunned to find only two workers amid 55 patients. The nurses were gone. Some were demanding higher wages for hazardous work, but many had simply left after seeing their colleagues become sick, he says. Patients were in beds and on the floor, the hospital contaminated.

“You get into a negative cycle in which it becomes a riskier environment for the nurses who do choose to keep working,” he says. “That happened in Kenema.” Even as basic public health measures slowed the outbreak in some other parts of Sierra Leone, it spun out of control in the region served by the Kenema hospital, he says.

Turning to drugs

In an opening salvo against the Ebola virus, six people have received a test drug called ZMapp, made by Mapp Pharmaceuticals of San Diego. But supplies of that compound are exhausted and making more will take months. So WHO and the U.S. Department of Health and Human Services have pulled together experts to pore over research on other candidate drugs and vaccines. The goal is to decide which products to put into rapid safety tests, says Bausch, who is among those advising WHO. In the best-case scenario, WHO officials say, some of these test drugs could reach the field later this year — after safety testing in human volunteers. All have so far been tested only in monkeys and other animals. While ZMapp uses antibodies, other approaches combine that strategy with other antiviral agents or use RNA interference to thwart the virus.

Having a drug, even an imperfect one, would have an impact beyond the individuals receiving it, Bausch says. A drug could change the mindset of people who have been in contact with patients but who are not themselves sick. Many hesitate to get tested because hospitals have no way to treat Ebola, he says. Refusal to get tested extends disease transmission if these contacts turn out to harbor the virus and develop an infection. Word of a drug could induce people to come in for testing. “Getting them out of circulation,” he says, “could end the outbreak.”

While giving experimental drugs such as ZMapp to patients has passed muster with bioethicists, the use of such drug candidates would still leave scientists with a poor understanding of how effective they are. About half of Ebola patients in West Africa survive without treatment, says physician Kevin Donovan of Georgetown University, making it difficult to distinguish whether a survivor who received a trial drug benefited from it.

Vaccines could play a role as well. WHO Assistant Director-General Marie-Paule Kieny said at an August 12 news briefing that safety testing of two experimental Ebola vaccines could start in late September. One comes from Canada’s National Microbiology Laboratory in Winnipeg, which announced last week that it will make available 800 to 1,000 doses of a vaccine that tested well in monkeys. Another vaccine is being readied by U.S. federal labs and GlaxoSmithKline. WHO will oversee who gets any test vaccines, with distribution unlikely until 2015.

Doctors, nurses and other clinical staff will be at the front of the line for such shots, says William Schaffner, an infectious disease physician at Vanderbilt University in Nashville, Tenn. “A lot of transmission occurs during the course of health care,” he says. Having a vaccine could encourage health care workers to stay on the job.

Unregulated travel by boat and other means in West Africa makes it difficult to contain transmission of the Ebola virus.

CDC

Nearly 10 percent of deaths in this outbreak have occurred in health care workers, says Kieny, adding that laboratory workers and those burying bodies would get high priority for vaccination as well.

But a lightly tested vaccine would come with caveats. It is unknown whether a single dose will protect fully, Schaffner says, so vaccinated health care workers will have to keep their guard up. They will need to continue to don biohazard suits and take other extraordinary precautions. If a vaccinated person comes down with Ebola, he says, it would hurt vaccine credibility.

Giving an experimental vaccine to relatives or other contacts of patients would seem like the next logical step, Bausch says, but could be difficult and might not yield much information about the vaccine. Those living amid the Ebola outbreak might well distrust the idea of getting a shot they may not need, and might not welcome later visits to their homes to draw blood to test for immune responses, Bausch says. “There’s an incredible stigma” attached to having Ebola in West Africa, he says. Even survivors “don’t admit they had it.”

That could complicate work on another treatment approach, called a “convalescent serum.” It would be derived from the blood of an infected person who had fended off the virus and developed antibodies against it. That research is still in its early stages, he says.

Worst one yet

Two dozen Ebola outbreaks have hit Africa since 1976. The current one has caused far more casualties than any other, WHO says, even though public health authorities have taken the same approach used previously: identifying and isolating infected people, tracing contacts of ill people for 21 days and having health care workers wear spacesuit-looking biohazard gear when monitoring the sick or handling dead bodies.

While the endgame for this Ebola outbreak remains as unclear as the animal that passed the virus to people (SN Online: 8/11/14), better understood is how the outbreak spun out of control, despite the efforts of Doctors Without Borders and other groups on the ground in Africa. “Resources were spread pretty thin early on,” says Thomas Geisbert, a virologist at the University of Texas Medical Branch at Galveston.

The extensive surveillance of contacts that had contained transmission in past outbreaks wasn’t achievable in West Africa, and rumors and misinformation have plagued work there. Episodes of lawlessness have complicated matters. Last weekend looters stormed a Liberian hospital and took mattresses and other infected supplies, risking further virus transmission.

Keiji Fukuda, WHO assistant director-general for health security, says WHO is targeting resources in the region where the three countries come together, including the Kenema area. “This is a consistent big hot spot,” he says. “It’s important to put this out.”

Nigeria also has 12 cases of Ebola, all stemming from an infected individual who flew there from Liberia. The sick people are being isolated, and more than 200 of their contacts are being monitored. Scientists hope the Nigeria mini-outbreak can be quelled. “But the jury is still out,” Bausch says.

Robots start flat, then pop into shape and crawl :

A new crawling robot has taken a page from origami design.

The machine’s paper-and-plastic  body can spring from flat to 3-D just like a pop-up book, researchers report in the Aug. 8 Science. And the action is automatic.

Engineers have built gizmos that can do some self-folding, but they also required hands-on help from humans. By embedding heaters in the robot’s hinges, Harvard microrobotics engineer Sam Felton and colleagues created a device that shifts shape on its own, using preprogrammed temperature changes.

A tiny onboard computer tells the heaters which hinges to warm first. The hinges are made of a polymer that contracts when heated, pulling the robot’s parts together. When the hinges cool, they lock into a folded position. Then two motors jiggle the bot’s legs, making the machine shimmy along in a slow crawl.

Self-folding devices like the robot could save room on spacecraft, or could even transform into portable shelters.

                  -source : science origin lab int/usa - sci678/narayanaa2000

‘NOVA’ takes science’s side in vaccine debate :

In some quarters, vaccines have become victims of their own success. Having suppressed the diseases they target, vaccines have left room for people to worry more about the shot than the illness. In response, the TV seriesNOVA offers an engrossing, evenhanded documentary, one that would never have been made 55 years ago, when people were happily lining up around the block to get polio shots.

Distrust of vaccines means that California today has an epidemic of whooping cough and Britain and France have faced bouts with measles. Some parents delay or skip vaccines mistakenly thinking they’re protecting their kids from autism or other problems. “Vaccines — Calling the Shots” dispels this nonsense.

Building the science from the bottom up, the filmmakers use nifty animation to show how a shot whips the immune system into action, putting memory cells on layaway in case the real disease shows up. Other dazzling graphics track a measles outbreak among unvaccinated people in Brooklyn.

The documentary then turns to the doctor’s office.

Viewers watch from a discreet angle as an Oklahoma City pediatrician asks a mother and teen daughter about vaccinating the girl against sexually transmitted human papillomavirus, which can cause cancers of the cervix and throat. The mother demurs, voicing concerns about teen sexuality and stressing abstinence. They skip the shot. 

In the next scene, a woman across town breaks down describing how her 37-year-old daughter died of cervical cancer, having grown up before the HPV shot was available. She would give anything to have vaccinated her girl.

NOVA doesn’t hide the fact that all medicines, including vaccines, carry risks. About 1 child out of every 1 million vaccinated will have a serious reaction. It’s a question of risk versus benefit, one scientist says, and it’s not even close.

Perhaps the program will get through to people who still doubt vaccines. Published science hasn’t fully done the trick, and pediatricians are left to tussle with resistant parents. A better approach might be to focus on the next generation: Show this first-rate documentary to middle school kids. 

                   -source : sci678/narayanaa2000

Neurons in silk scaffold mimic behaviors of a real brain : 

It may look like a child’s stacking toy, but a colorful assembly of concentric layers is actually a three-dimensional model of a brain. A series of porous doughnuts, made from proteins taken from silkworm cocoons, serve as scaffolds for rat nerve cells to populate.

The neurons grew in the scaffold for weeks and, in some ways, began behaving as if they were in a real brain, scientists report August 11 in the Proceedings of the National Academy of Sciences. After a hard thump from a weight, meant to mimic a traumatic brain injury, neurons in the brain model showed signs of damage, including a burst of activity. The new model might allow scientists to better understand how brain cells respond to injuries.

For more on building brains, read SN's Tiny human almost-brains made in lab. 

                       - Source - Science origin international lab-sci678/narayanaa2000.