The Boston Citgo sign, all 3,600 square LED feet of which has served as the backdrop to Red Sox games since 1965, is now officially a "pending landmark."

Spanish Surrealist Salvador Dalí spent much of the 1940s in the U.S., avoiding World War II and its aftermath. He was a well-known fixture on the art scene in Monterey, Calif. — and that's where the largest collection of Dalí's work on the West Coast is now open to the public.

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The middle of summer is when the surprises in publishing turn up. I'm talking about those quietly commanding books that publishers tend to put out now, because fall and winter are focused on big books by established authors. Which brings us to The Dream Life of Astronauts, by Patrick Ryan, a very funny and touching collection of nine short stories that take place in the 1960s and '70s around Cape Canaveral, Fla.

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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.


Experimental Tuberculosis Vaccine Fails To Protect Infants

Feb 4, 2013
Originally published on February 4, 2013 6:03 pm

Researchers are disappointed in the results of a long-awaited study of the leading candidate vaccine against tuberculosis, one of humankind's most elusive scourges.

But, pointing to more than a dozen other TB vaccines in the pipeline, they say they're not discouraged.

The results show that an experimental vaccine known as MVA85A didn't provide much protection for South African infants against either infection with TB or development of the disease.

Earlier, smaller studies in adults and in animals raised the hope that the vaccine might work. But the infants had immune responses to MVA85A only a tenth as strong as adults did.

"Clearly this is a disappointment," says Helen McShane of Oxford University, who developed MVA85A and led the South African trial. "It's not what we hoped for or expected. But what we have learned from this trial will help us in the whole field."

There hasn't been a study of TB vaccine in infants for 45 years, when a large trial affirmed the partial efficacy of what is still the only TB vaccine, called Bacille Calmette-Guerin, or BCG.

Every year more than 100 million babies around the world receive BCG, a live but weakened version of a bovine TB germ that was developed 92 years ago. But while BCG can prevent tuberculosis that has spread beyond the lungs, it doesn't reliably protect against pulmonary TB, the most severe form.

MVA85A is designed to boost the effect of BCG. All the infants in the South African study received BCG; half of them got the experimental vaccine while the others got a placebo, actually a skin test antigen, or immune stimulator, from a fungus called candida.

In combination with BCG, the study vaccine did what it was supposed to in infants: stimulate immune cells called CD4s to produce immune responses specific to TB. But the response was only modest, and clearly not enough to protect the babies against either TB infection or disease.

Among the nearly 2,800 children in the study, 13 percent got infected with TB over the 37-month course of the trial – an indicator of how alarmingly common the disease is in South Africa. About 1 in 20 people there die of TB, and a growing number are getting strains that are difficult to quell with first- and even second-line drugs.

Thirty-nine of the infants in the placebo group developed TB versus 32 who got the experimental vaccine. That means MVA85A was 17.3 percent effective in preventing TB. "But that's not statistically significant, so we can't determine if that effect was real or not," McShane told reporters Monday during a teleconference from London.

Despite the disappointment with the experimental vaccine in infants, the findings "are not a terminal prognosis for MVA85A or for any of the other tuberculosis vaccines in development," Christopher Dye and Paul E.M. Fine write in an editorial that accompanies the findings in The Lancet.

Like the study authors, Dye and Fine point out that there are a half-dozen other ways in which MVA85A might still prove useful.

For instance, judging from preliminary studies, the vaccine might protect against TB infection or disease in adults. Researchers would like to try MVA85A alone, as well in combination with BCG, in larger studies with adults.

And they think it's worth trying it in people infected with HIV, because as a live-attenuated vaccine BCG isn't thought to be safe to use in people with HIV-damaged immune systems.

Meanwhile, at least two other experimental TB vaccines are in advanced trials, according to Dr. Thomas Evans of Aeras, a nonprofit developer of TB vaccines that sponsors MVA85A and about half the experimental vaccines in the pipeline.

"The results will take a few years," Evans says. "So it's not around the corner, but they are in the queue and moving forward."

Of the newly published results, Evans says: "This trial leaves us optimistic, not pessimistic. Ten years ago, many doubted such a trial could be completed ...."

And McShane adds, 10 years ago the technology didn't exist to develop and test novel vaccines aimed at stimulating the so-called cellular immune response, which attacks and kills cells already infected with a bacterium or virus. Classical vaccines stimulate the other arm of the immune system, which makes antibodies.

"TB hides inside cells, which means it's difficult for the immune system to get at," McShane says. Moreover, like HIV, it can persist in a latent form for a lifetime. "It's a very clever pathogen," she says.

And as the new findings make very clear, researchers are only in the very early stages of figuring out just what it will take to prevent TB infection or disease.

One detail in this study underscores what TB researchers are up against. The authors note that the experimental vaccine may only be effective against severe forms of TB, not the mild cases that develop in newly infected infants.

However, it would take a "prohibitively large" study to test the efficacy of a vaccine in preventing severe TB, the authors note.

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