When the United Kingdom voted to leave the European Union last month, the seaside town of Port Talbot in Wales eagerly went along with the move. Brexit was approved by some 57 percent of the town's residents.

Now some of them are wondering if they made the wrong decision.

The June 23 Brexit vote has raised questions about the fate of the troubled Port Talbot Works, Britain's largest surviving steel plant — a huge, steam-belching facility that has long been the town's biggest employer.

Solar Impulse 2 has landed in Cairo, completing the penultimate leg of its attempt to circumnavigate the globe using only the power of the sun.

The trip over the Mediterranean included a breathtaking flyover of the Pyramids. Check it out:

President Obama is challenging Americans to have an honest and open-hearted conversation about race and law enforcement. But even as he sits down at the White House with police and civil rights activists, Obama is mindful of the limits of that approach.

"I've seen how inadequate words can be in bringing about lasting change," the president said Tuesday at a memorial service for five law officers killed last week in Dallas. "I've seen how inadequate my own words have been."

Mice watching Orson Welles movies may help scientists explain human consciousness.

At least that's one premise of the Allen Brain Observatory, which launched Wednesday and lets anyone with an Internet connection study a mouse brain as it responds to visual information.

The FBI says it is giving up on the D.B. Cooper investigation, 45 years after the mysterious hijacker parachuted into the night with $200,000 in a briefcase, becoming an instant folk figure.

"Following one of the longest and most exhaustive investigations in our history," the FBI's Ayn Dietrich-Williams said in a statement, "the FBI redirected resources allocated to the D.B. Cooper case in order to focus on other investigative priorities."

This is the first in a series of essays concerning our collective future. The goal is to bring forth some of the main issues humanity faces today, as we move forward to uncertain times. In an effort to be as thorough as possible, we will consider two kinds of threats: those due to natural disasters and those that are man-made. The idea is to expose some of the dangers and possible mechanisms that have been proposed to deal with these issues. My intention is not to offer a detailed analysis for each threat — but to invite reflection and, hopefully, action.

Alabama authorities say a home burglary suspect has died after police used a stun gun on the man.  Birmingham police say he resisted officers who found him in a house wrapped in what looked like material from the air conditioner duct work.  The Lewisburg Road homeowner called police Tuesday about glass breaking and someone yelling and growling in his basement.  Police reportedly entered the dwelling and used a stun gun several times on a white suspect before handcuffing him.  Investigators say the man was "extremely irritated" throughout and didn't obey verbal commands.

It can be hard to distinguish among the men wearing grey suits and regulation haircuts on Pennsylvania Avenue in Washington. But David Margolis always brought a splash of color.

It wasn't his lovably disheveled wardrobe, or his Elvis ring, but something else: the force of his flamboyant personality. Margolis, a graduate of Harvard Law School, didn't want to fit in with the crowd. He wanted to stand out.

Montgomery Education Foundation's Brain Forest Summer Learning Academy was spotlighted Wednesday at Carver High School.  The academic-enrichment program is for rising 4th, 5th, and 6th graders in the Montgomery Public School system.  Community Program Director Dillion Nettles, says the program aims to prevent learning loss during summer months.  To find out how your child can participate in next summer's program visit Montgomery-ed.org

A police officer is free on bond after being arrested following a rash of road-sign thefts in southeast Alabama.  Brantley Police Chief Titus Averett says officer Jeremy Ray Walker of Glenwood is on paid leave following his arrest in Pike County.  The 30-year-old Walker is charged with receiving stolen property.  Lt. Troy Johnson of the Pike County Sheriff's Office says an investigation began after someone reported that Walker was selling road signs from Crenshaw County.  Investigators contacted the county engineer and learned signs had been reported stolen from several roads.


Let's Look Beyond Random Trials When Assessing New Drug Treatments

Nov 19, 2012

In this post I report, in outline, a recent publication in PLOS ONE by Margaret Eppstein, Jeffrey Horbar, Jeff Buzas and myself, Stuart Kauffman. All four of us are at the University of Vermont, with Horbar also director of the Vermont Oxford Network of over 900 hospitals. I will refer to the four co-authors as "The Vermont Group." The full paper is entitled "Searching the Clinical Fitness Landscape".

Our work calls into question the adequacy of the criteria, the famous double blind randomized clinical trials, or RCT for "randomized controlled trial," upon which the FDA relies for testing drug safety and efficacy. Our work is meant both to examine the search for good combinations of treatment modalities on a day to day basis and may be of use in seeking useful combinations of drugs requiring multifactorial causal effects. In brief, our work shows that when RCTs work, they do really work, often well. But they often fail in complex biological-medical situations where causality is multifactorial, as it typically is. In place of RCT, our group has found a better alternative in these cases which we call "Team Learning."

The medical and societal implications may be large, as I describe below.

The Vermont Group created a simple mathematical model I need to explain. We supposed 100 treatment modalities, each with two discrete levels, low and high. Now imagine that all 100 modalities have totally independent modes of action. And arbitrarily, suppose that "high" is best on each of these 100 treatment modalities. Then "all 100 high," is the best that can be done to achieve some desired clinical outcome, say survival. The more "lows" chosen among the 100, the worse the outcome.

Think next of the "goodness" of the outcome as a "height," and in the case of 100 independent treatment modalities one achieves a single peaked "clinical landscape" rather like Mt. Fuji, with smooth sides.

But suppose the treatment modalities are not independent and interact in positive and negative ways. If this is true, causality is now "multifactorial." No single factor or modality acts alone to affect the outcome. Intuitively, this can and does create a clinical landscape with multiple "local peaks" of good outcomes.

In our model, we are able to tune how richly the 100 modalities interact. We tested two very different "learning strategies" on these single peaked and multipeaked clinical landscapes. The first is statistically rigorous double blind randomized clinical trials, RCT. Here from 400 to 3,200 patients were studied per trial. In RCT, the modality selected for testing is based on which treatments are more consistently used in the top 50 hospitals compared to the bottom 50 hospitals among a total 100 hospitals. The selected modality is tested once by a random 10 of the 100 hospitals, and adopted by all the 100 hospitals if statistically significant in the double blind experiment beyond the 5 percent level. Thereafter, that modality is not tested again. RCT performs well, with statistically rigorous results, when the 100 treatment modalities are independent.

But as the 100 treatment modalities interact ever more richly, RCT progressively fails. It does not achieve statistically significant results.

Team learning, emerging now in real teams of hospitals forming quality improvement collaboratives, is radically different.

In our model of real life team learning, we modeled 100 hospitals broken into 10 teams of 10 hospitals. Each hospital acted as a single "learning agent." Here is how a team "learns." Each of the 10 members of the team independently decides which of its 100 treatment modalities to try changing from "high to low" or "low to "high" by observing what appears to be working better among its team members. Specifically, it decides to try a new treatment value that has the highest relative prevalence among team members that have higher survival rates than at its own institution, compared to team members have have lower survival rates.

Each hospital then tries the new value of its selected modality back at its own institution, in combination with the other 99 treatments already in use there. This is tried on a relatively small number of patients, ranging from 40 per trial to 320 per trial. The new treatment is adopted if any improvement in survival is observed, without regard to statistical significance.

Then this search process iterates. During this, some hospital may chose a previously flipped treatment and flip it back from low to the former high.

In both RCT and Team Learning these iterations continue for 100 cycles. Stunningly, Team Learning outperforms RCT in virtually all cases. RCT only outperforms Team Learning on single-peaked "Fuji" landscapes when factors are fully independent and very large numbers of patients are enrolled in the trials.

This is only a first study. But do we know that causality in biology is multifactorial? Yes, it typically is. Polygeny in developmental biology has been known for many years. Here many genes contribute to one phenotype or "outcome." Causality here is multifactorial. Finally, I also want to note that surgery improves over time without using RCT; we cannot clone surgeons. So clinical multifactorial learning without RCT is perfectly possible.

If confirmed, what does this portend?

1) Although double blind randomized controlled trials will remain the gold standard for assessing the risks and benefits of novel therapies, it becomes very likely that the reliance of the medical profession and FDA on such studies, which when they work do work, is nevertheless too narrow a basis for clinical learning about good combinations of drugs to use or other combinations of treatment modalities. Team Learning is better at learning complex combinations of treatment modalities. Cells and organisms are networks causally. Effective control may require inputs at many points simultaneously, not single silver bullets. Thus over-reliance on single-factor RCT is probably throwing away clinically relevant information to all our loss.

2) That which is FDA approved strongly defines "best practice" medicine by which well trained doctors practice and are even constrained to practice, for fear of unscientific, even charlatan, medicine. But if "best practice" is based on too narrow an evidential basis, we all suffer.

3) We need to learn multifactorial medicine, some new combination of systems biology, complexity theory and medicine, an imposing task for the near future.

4) We may need to broaden our thinking and rethink rules which may be overly constrictive.

Copyright 2012 National Public Radio. To see more, visit http://www.npr.org/.