Thursday, January 20, 2011

FROM DUSTY PUNCH CARDS, NEW INSIGHTS INTO LINK BETWEEN CHOLESTEROL AND HEART DISEASE

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A stack of punch cards from a landmark study published in 1966, and the legwork to track down the study’s participants years later, has yielded the longest analysis of the effects of lipoproteins on coronary heart disease.

The study, published in a recent issue of the journal Atherosclerosis, tracked almost 1,900 people over a 29-year period, which is nearly three times longer than other studies that examine the link between different sizes of high-density lipoprotein particles and heart disease.

It found that an increase in larger high-density lipoprotein particles decreased a subject’s risk of heart disease. The research also underscores the value of looking to the past to advance science.

“Often we think only of designing new studies with the latest technologies, but there are treasures buried in our past,” says study author Paul Williams of the U.S. Department of Energy’s Lawrence Berkeley National Laboratory.

Lipoproteins are fat molecules that carry cholesterol in the blood. Cholesterol is divided into high-density lipoprotein, the so-called good cholesterol, and low-density lipoprotein, the bad cholesterol.

That’s common knowledge today. But it was a groundbreaking and controversial notion in the 1950s, when Berkeley Lab’s John Gofman used an analytic ultracentrifuge at Berkeley Lab to separate and measure the different lipoproteins. He was the first to propose that high-density and low-density lipoprotein particles play a role in heart disease.

His research was met with skepticism, however, so Gofman began a prospective study of lipoproteins in a group of 1,905 employees at Lawrence Livermore National Laboratory between 1954 and 1956. After ten years, there were 38 new cases of heart disease. In 1966, he reported that men who developed heart disease had lower levels of the HDL2 (the larger high-density lipoprotein particles) and HDL3 (the smaller high-density lipoprotein particles).

It would take several more years for Gofman’s work to gain currency in the scientific community. Gofman left lipoprotein research in the 1960s to pioneer the study of the biological effects of low doses of radiation. He died in 2007.

His Livermore cohort study collected dust until 1988, when Williams discovered the study’s punch cards at the University of California, Berkeley’s Donner Hall. Realizing he had found an epidemiological goldmine, Williams verified the cards’ authenticity by examining logbooks. He also found an old punch card machine to extract their data. Then, with the help of students and research assistants, he located and contacted 97 percent of the people in Gofman’s study over the next nine years.

“Often, all we had to go on was an address on a street that no longer existed,” says Williams, a staff scientist in Berkeley Lab’s Life Sciences Division. “Women had changed their names, employees had left or retired and moved, and many had died. However, by telephoning neighbors and coworkers, we were able to track down all but a few.”

Medical records were obtained and reviewed by a physician, Daniel Feldman, who is the study’s co-author.

Their 29-year follow-up uncovered 363 cases of coronary heart disease. They found that both HDL2 and HDL3 lowered heart disease risk, and that a one-milligram per milliliter increase in HDL2 produced a significantly larger reduction in coronary heart disease risk than a one-milligram per milliliter increase in HDL3. Their follow-up also buttressed Gofman’s insights from 1966.

“Gofman’s original conclusion that ischemic heart disease is inversely related to both HDL2 and HDL3 was upheld in the current analyses,” says Williams, who hopes to complete the 55-year follow-up of this cohort.

(Photo: LBNL)

Lawrence Berkeley National Laboratory

WHAT TRIGGERS MASS EXTINCTIONS? STUDY SHOWS HOW INVASIVE SPECIES STOP NEW LIFE

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An influx of invasive species can stop the dominant natural process of new species formation and trigger mass extinction events, according to research results published in the journal PLoS ONE.

The study of the collapse of Earth's marine life 378 to 375 million years ago suggests that the planet's current ecosystems, which are struggling with biodiversity loss, could meet a similar fate.

Although Earth has experienced five major mass extinction events, the environmental crash during the Late Devonian was unlike any other in the planet's history.

The actual number of extinctions wasn't higher than the natural rate of species loss, but very few new species arose.

"We refer to the Late Devonian as a mass extinction, but it was actually a biodiversity crisis," said Alycia Stigall, a scientist at Ohio University and author of the PLoS ONE paper.

"This research significantly contributes to our understanding of species invasions from a deep-time perspective," said Lisa Boush, program director in the National Science Foundation (NSF)'s Division of Earth Sciences, which funded the research.

"The knowledge is critical to determining the cause and extent of mass extinctions through time, especially the five biggest biodiversity crises in the history of life on Earth. It provides an important perspective on our current biodiversity crises."

The research suggests that the typical method by which new species originate--vicariance--was absent during this ancient phase of Earth's history, and could be to blame for the mass extinction.

Vicariance occurs when a population becomes geographically divided by a natural, long-term event, such as the formation of a mountain range or a new river channel, and evolves into different species.

New species also can originate through dispersal, which occurs when a subset of a population moves to a new location.

In a departure from previous studies, Stigall used phylogenetic analysis, which draws on an understanding of the tree of evolutionary relationships to examine how individual speciation events occurred.

She focused on one bivalve, Leptodesma (Leiopteria), and two brachiopods, Floweria and Schizophoria (Schizophoria), as well as a predatory crustacean, Archaeostraca.

These small, shelled marine animals were some of the most common inhabitants of the Late Devonian oceans, which had the most extensive reef system in Earth's history.

The seas teemed with huge predatory fish such as Dunkleosteus, and smaller life forms such as trilobites and crinoids (sea lilies).

The first forests and terrestrial ecosystems appeared during this time; amphibians began to walk on land.

As sea levels rose and the continents closed in to form connected land masses, however, some species gained access to environments they hadn't inhabited before.

The hardiest of these invasive species that could thrive on a variety of food sources and in new climates became dominant, wiping out more locally adapted species.

The invasive species were so prolific at this time that it became difficult for many new species to arise.

"The main mode of speciation that occurs in the geological record is shut down during the Devonian," said Stigall. "It just stops in its tracks."

Of the species Stigall studied, most lost substantial diversity during the Late Devonian, and one, Floweria, became extinct.

The entire marine ecosystem suffered a major collapse. Reef-forming corals were decimated and reefs did not appear on Earth again for 100 million years.

The giant fishes, trilobites, sponges and brachiopods also declined dramatically, while organisms on land had much higher survival rates.

The study is relevant for the current biodiversity crisis, Stigall said, as human activity has introduced a high number of invasive species into new ecosystems.

In addition, the modern extinction rate exceeds the rate of ancient extinction events, including the event that wiped out the dinosaurs 65 million years ago.

"Even if you can stop habitat loss, the fact that we've moved all these invasive species around the planet will take a long time to recover from because the high level of invasions has suppressed the speciation rate substantially," Stigall said.

Maintaining Earth's ecosystems, she suggests, would be helped by focusing efforts and resources on protection of new species generation.

"The more we know about this process," Stigall said, "the more we will understand how to best preserve biodiversity."

(Photo: Ohio University)

National Science Foundation

TRUST YOUR GUT... BUT ONLY SOMETIMES

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When faced with decisions, we often follow our intuition—our self-described “gut feelings”—without understanding why. Our ability to make hunch decisions varies considerably: Intuition can either be a useful ally or it can lead to costly and dangerous mistakes. A new study published in Psychological Science, a journal of the Association for Psychological Science, finds that the trustworthiness of our intuition is really influenced by what is happening physically in our bodies.

“We often talk about intuition coming from the body—following our gut instincts and trusting our hearts”, says Barnaby D. Dunn, of the Medical Research Council Cognition and Brain Sciences Unit in Cambridge, U.K., first author of the new paper. What isn’t certain is whether we should follow, or be suspicious of, what our bodies are telling us. And do we differ in the influence that our gut feelings have on how we make decisions?

To investigate how different bodily reactions can influence decision making, Dunn and his co-authors asked study participants to try to learn how to win at a card game they had never played before. The game was designed so that there was no obvious strategy to follow and instead players had to follow their hunches. While playing the game, each participant wore a heart rate monitor and a sensor that measured the amount of sweat on their fingertips.

Most players gradually found a way to win at the card game and they reported having relied on intuition rather than reason. Subtle changes in the players’ heart rates and sweat responses affected how quickly they learned to make the best choices during the game.

Interestingly, the quality of the advice that people’s bodies gave them varied. Some people’s gut feelings were spot on, meaning they mastered the card game quickly. Other people’s bodies told them exactly the wrong moves to make, so they learned slowly or never found a way to win.

Dunn and his co-authors found this link between gut feelings and intuitive decision making to be stronger in people who were more aware of their own heartbeat. So for some individuals being able to ‘listen to their heart’ helped them make wise choices, whereas for others it led to costly mistakes.

“What happens in our bodies really does appear to influence what goes in our minds. We should be careful about following these gut instincts, however, as sometimes they help and sometimes they hinder our decision making,” says Dunn.

Association for Psychological Science

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