RealClearScience Journal Club

Science Figures Interpreted and Analyzed by RealClearScience

Cachexia: Why Cancer Patients Waste Away

Alex B. Berezow - November 24, 2015

One of the most pernicious conditions that arises as a consequence of cancer is a sort of wasting syndrome. More formally known as cachexia, it causes patients to lose body mass (including both muscle and fat) and to grow weak and fatigued. Whether or not a patient develops cachexia largely depends on the type of cancer he has. Those with pancreatic cancer, for instance, have an 80% chance of suffering from it, while those with breast cancer have a 40% chance. The syndrome takes such a physical toll on the patient that it is largely to blame for a fifth of all cancer deaths. Cachexia, therefore, remains one of the most heartbreaking and puzzling aspects of cancer.

An article published last year in the journal Nature Reviews Cancer attempts to shed light on the molecular mechanisms underlying the condition. The authors believe that the existing evidence points to cachexia being a multi-organ syndrome that results from metabolic inefficiency, wasting of muscle and fat tissue, and systemic inflammation.

An example of metabolic inefficiency is a futile cycle; that is, a vicious cycle that does nothing productive and wastes energy in the form of heat. Tumors tend to gobble up glucose, a valuable source of energy, and convert it to pyruvate, a waste product. The liver accepts the pyruvate and, in cachexic patients, converts it back to glucose (which uses up energy), before shipping it back to the tumor. Simultaneously, the energy-producing structures, called mitochondria, inside muscle cells start to malfunction.

Worsening the problem for muscle cells is a total disruption of normal metabolism. Muscles begin exporting glutamine, an amino acid, into the bloodstream, after which it is imported by the tumor. This results in nitrogen starvation in the muscle cells. Furthermore, inflammatory molecules induced by the tumor tell muscle cells to destroy proteins and commit suicide. The ultimate result is muscle wasting. Similarly, metabolic changes inside fat tissue causes it to atrophy, as well. One such change is the diversion of mitochrondia from the production of energy "currency" (molecules called ATP) to the production of waste heat.

Underlying all of these perturbations is systemic inflammation. Tumors activate the immune system, which in turn releases messenger molecules that severely disrupt normal physiology by triggering the dysfunction described above. Besides muscles and fat tissue, cachexia also disturbs the brain, liver, gut, and heart. The brain, for example, begins to suppress appetite. (See figure.)

Source: JM Argilés et al. Nat Rev Cancer 14 (11): 754-62.

As if all of this weren't bad enough, the side effects of chemotherapy and radiation therapy tend to aggravate cachexia.

Can anything be done to stop cachexia? Perhaps, but it must be addressed before it becomes late-stage, which is untreatable. One potential therapy, described by Cosmos Magazine, involves using antibodies against a protein produced by cancer cells called Fn14. In mice, these antibodies effectively blocked cachexia. Human clinical trials may be on the way.

The other good news is, though it certainly doesn't feel like it, we are slowly winning the war on cancer.

Source: Josep M. Argilés, Sílvia Busquets, Britta Stemmler and Francisco J. López-Soriano. "Cancer cachexia: understanding the molecular basis." Nat Rev Cancer 14 (11):754-62. Published online: 9-Oct-2014. doi: 10.1038/nrc3829.

(AP photo)

Pigeons Can Be Taught Pathology and Radiology

Ross Pomeroy - November 19, 2015

A new study shows that pigeons can be trained to recognize breast cancer with surprising accuracy.

The research was published yesterday to PLoS ONE.

In the past, pigeons have been trained to recognize letters of the alphabet, identify human emotions, and even differentiate paintings by Monet and Picasso, but evaluating medical imagery was an entirely novel foray.

Researchers primarily based out of the University of Iowa trained eight pigeons to differentiate between images of benign and malignant breast cancer slides at varying levels of magnification. In just a couple of weeks, the birds' accuracy rose from 50% to 85%.

At the conclusion of the training phase, the researchers challenged the birds with images they'd never seen before, and incredibly, the birds correctly identified 85% of the new images, indicating that they had somehow learned to detect the defining features of breast cancer.

In a second experiment, the researchers trained four different birds to detect microcalcifications from mammograms (seen below), an early sign of cancer. Again, the pigeons attained an average 85% accuracy after two weeks. When presented with novel images, they correctly identified 69% percent of the images with microcalcifications, which was significantly better than chance, but not nearly as good as their earlier performance with breast tissue. Human radiologists and radiology residents given the same cases to review averaged 97% accuracy for images without calcifications and 70% for images with them.

Lastly, the researchers challenged four pigeons to discern between benign and malignant masses on mammograms (shown below). This time the birds never really got the hang of it. After twelve weeks of training, just two pigeons were able to differentiate the images at accuracies approaching 80%, and when presented with novel images, they performed no better than chance. A panel of radiologists achieved an accuracy rate of about 80% when viewing the same images, much better than the pigeons.

While the results of the study are fairly remarkable, especially for animals with brains no bigger than the tip of an index finger, it doesn't seem that pigeons are ready for white coats just yet.

Source: Levenson RM, Krupinski EA, Navarro VM, Wasserman EA (2015) Pigeons (Columba livia) as Trainable Observers of Pathology and Radiology Breast Cancer Images. PLoS ONE 10(11): e0141357. doi:10.1371/journal.pone.0141357

Real-Time Reaction Polls Distort TV Debates

Alex B. Berezow - November 17, 2015

A few election cycles ago, a new feature was introduced to televised debates: The real-time reaction tracker. A small focus group of two dozen or so individuals use dials to indicate how much they agree or disagree with the statements being made by politicians during the debate. An aggregated average of these responses is then displayed in real-time for the viewing audience to see. Fascinatingly, this instant reaction poll appears to influence the opinions of the millions of people watching the debate at home.

A study published a few years ago in PLoS ONE took advantage of the 2010 parliamentary election in Britain to examine the issue. Students, who were misled to believe that they were attending a study on memory, were assigned to different rooms which were broadcasting the final debate. Unbeknownst to them, the real-time tracker (a.k.a. "the worm") was being manipulated behind the scenes. In one room, the worm was biased in favor of Gordon Brown (the incumbent Prime Minister); in the other, it was biased in favor of Nick Clegg (the leader of the Liberal Democrats).

After the debate, the students were asked to judge who won. The results are shown below:

Most importantly, students' voting intentions were also swayed in the direction of the bias of the worm.

Oddly, the researchers exposed students neither to a "control worm" nor to a worm biased in favor of David Cameron (leader of the Conservative Party). They did, however, ask random students the following day who they thought won the debate, but this is not a sufficient control.

Yet, despite the sloppy experimental design, the results are striking enough to be convincing. Though voters like to think of themselves as independently minded, the reality is that they are rather easily influenced by the opinions of others. Let us hope, therefore, that the media outlets and pollsters who conduct tracking polls aren't lying to us.

Source: Davis CJ, Bowers JS, Memon A (2011) Social Influence in Televised Election Debates: A Potential Distortion of Democracy. PLoS ONE 6(3): e18154. doi:10.1371/journal.pone.0018154

(AP photo)

Americans Greatly Overestimate Economic Mobility

Ross Pomeroy - November 13, 2015

Americans greatly overestimate social and economic mobility in the United States, and the effect is most pronounced among younger Americans, conservatives, and those who perceive themselves to be in a higher social class.

America was founded on the notion that hard work and perseverance will bring success and elevate an individual in society; that's the essence of the American Dream. Yet that notion is increasingly unrealistic for Americans who start out on the lower rungs of the socioeconomic ladder.

Population data on social class mobility in the United States collected between the years of 1996 and 2007 show that less than one percent of people from the bottom 20% of income (less than $18,500 for a household) moved to the top 20% of income (more than $92,000), and roughly one in ten individuals move out of the bottom 20% by working 1,000 extra hours.

Last year, Michael Kraus of Yale University and Jacinth Tan of the University of Illinois recruited 752 participants from Amazon's Mechanical Turk and asked them to estimate social class mobility. Specifically, they questioned them on the aforementioned data. Participants' estimates were way off. They guessed that sixteen percent would rise from the bottom 20% to the top 20%, and 35% of people would make it out of the bottom 20% by working 1,000 extra hours. Once again, the actual numbers are less than one percent and roughly one in ten. The subjects also greatly overestimated the proportion of people able to move out of the bottom 20% by attaining some sort of degree (estimate = 60%, actual = 30%).

These results were published in the Journal of Experimental and Social Psychology.

When Kraus and Tan further dived into the data, they found that participants who were younger, more conservative, or who perceived themselves to be from a higher social class were more likely to overestimate mobility.

On Monday, Kraus published a replication of his study, this time in the journal Frontiers in Psychology. Everything was completed exactly as in the first study albeit with a different set of 747 participants.

The results were nearly identical. Participants once again widely overestimated economic and social mobility, with younger participants, conservatives, and those perceiving themselves to be from a higher social class tendering the highest overestimates.

The replicated results provide additional support for an interpretation that Kraus provided in his original study.

"Perceptions of elevated position in the class hierarchy motivate beliefs that class mobility is fair, just, and possible for many average Americans."

Unfortunately, as actual data demonstrates, these beliefs appear to be erroneous.

On the replicated study, Kraus added, "The current results provide additional evidence consistent with the idea that people overestimate class mobility to protect their beliefs in the promise of equality of opportunity."


Kraus MW (2015) Americans Still Overestimate Social Class Mobility: A Pre-Registered Self-Replication. Front. Psychol. 6:1709. doi: 10.3389/fpsyg.2015.01709

Kraus, M. W., and Tan, J. J. X. (2015). Americans overestimate social class mobility. J. Exp. Soc. Psychol. 58, 101–111. doi: 10.1016/j.jesp.2015.01.005

The Sahara Once Had a Mighty River System

Ross Pomeroy - November 10, 2015

The Western Sahara may once have been home to a vast river system that -- if it were still around today -- would rank as the twelfth largest drainage basin worldwide. The finding is detailed in today's issue of Nature Communications.

The Sahara Desert covers roughly a quarter of Africa and is comparable in size to the continental United States. Equally awesome to viewing the desert's seemingly endless waves of sand dunes is seeing the Sahara from outer space. Lush green gives way to a solid, arid ocean of white, tan, and brown, almost as if the Earth forgot to color in the landscape. Little to no rain falls throughout, but the region does give birth to massive storms of dust, which plume out into the Atlantic Ocean.

In fact, dust, or more specifically, sediment, is what clued researchers in to the possible existence of an ancient river system in the Western Sahara. Many samples of deep sea sediments taken off the coast of Western Africa seem more typical of river-borne material than ocean-borne material, implying that a river once emptied into the ocean in the area. Geographical and climate models lent credence to the idea, but hard data was lacking.

A team of French researchers has now filled that void by using a sophisticated imaging system onboard the Japanese Advanced Land Observing Satellite. The sensor system, called PALSAR, is capable of imaging geological features buried under layers of sediment, in this case, sand, lots of sand. Pointing the satellite at the coastal section of Mauritania, the researchers spotted a large drainage system that was almost certainly connected to a long, meandering river system.


The longer river system, called the Tamanrasett, may have extended across a significant portion of the Sahara. The researchers estimate that it may have held flowing water as many as nine times in the past 245,000 years, including as recently as 6,000 years ago during a so-called African Humid Period. These periods of climatic change in the region happen as a result of tiny variations in Earth's orbit around the sun, and seem to occur regularly every 20,000 years or so.

The presence of the river system suggests that the Sahara was once much greener than it is today, and could very well be so again.

Source: Skonieczny, C. et al. African Humid periods triggered the reactivation of a large river system in Western Sahara. Nat. Commun. 6:8751 doi: 10.1038/ncomms9751 (2015).

New Sponge Absorbs, Releases Oil on Demand

Alex B. Berezow - November 10, 2015

As long as the global economy relies on oil, oil spills are a constant hazard. Devising innovative and efficient ways to clean up the messes is, therefore, a top environmental priority. Now, a team of Korean researchers has designed a "nano-sponge" that absorbs and desorbs oil on demand. And, unlike many other materials used to clean up oil spills, their invention is reusable. The researchers published the details in the journal Scientific Reports.

The authors coated sponges, made from polydimethylsiloxane, with nanoparticles created from a mixture of 60% hydrocarbons and 40% titanium dioxide. The sponge repels water (colored red in the photo to the left) but absorbs crude oil (black). (In chemist-speak, the sponge is hydrophobic and oleophilic.)

Next, the authors showed how their sponge works once submerged in water contaminated with crude oil. (See figure below.) Because it is oil-loving (oleophilic), the sponge soaks up the crude oil and turns black. Bubbles emerge as the oil fills up air pockets. Then, the authors irradiated the sponge with UV light. Titanium dioxide behaves differently in UV light, becoming extremely water-loving (superhydrophilic). Because of this change, the sponge is now more attracted to water than it is to oil. When combined with aeration (i.e., bubbles), the UV-irradiated sponge releases the oil it had just absorbed. 

The authors subsequently demonstrated that 98% of the absorbed oil could be released by the sponge, meaning that it can be used over and over again. (See figure below.)

The researchers should be commended on an extremely clever invention. One hopes they are seeking to commercialize this product.

Source: Do Hyun Kim, Min Chan Jung, So-Hye Cho, Sang Hoon Kim, Ho-Young Kim, Heon Ju Lee, Kyu Hwan Oh & Myoung-Woon Moon. "UV-responsive nano-sponge for oil absorption and desorption." Scientific Reports 5, Article number: 12908. Published online: 11-August-2015. doi: 10.1038/srep12908

(AP photo)

Hair Test for Marijuana Proves Nothing

Alex B. Berezow - November 3, 2015

There are few things that pot enthusiasts dread more than the unannounced drug test. A positive test for THC, the active ingredient in marijuana, can result in the loss of a job or child custody. But new research by a team of German scientists suggests that detecting THC in a hair sample doesn't prove cannabis consumption.

To understand why, it is first necessary to explain the basic chemistry of THC metabolism. (See bottom part of figure.)

The molecule found in fresh marijuana, THCA-A, easily converts to the psychoactive THC upon heating. (That is why marijuana is smoked or baked into brownies.) After consuming it, the body converts THC into 11-nor-9-carboxy-THC (a.k.a. THC-COOH). Presence of this molecule in hair is considered definitive proof that a person consumed pot. However, due to its low concentration, it is difficult to detect. As a result, most hair tests only look for the presence of THC. However, according to the latest study, this is very problematic.

Two volunteers who had neither used nor were anywhere near marijuana prior to the study consumed 2.5 mg THC three times per day for 30 days. Despite having detectable levels of THC in their blood, the team found no trace of THC in their hair. This suggests that the only way for THC to get into a person's hair is through the environment. Thus, a negative test for THC proves absolutely nothing (as a person could eat a pot brownie and still produce a negative test result). Far more disturbingly, a nonsmoker who spends time with pot smokers may produce a positive result on a THC hair test.

The metabolite 11-nor-9-carboxy-THC (THC-COOH) was found in both blood and hair samples from the volunteers. However, the hair samples contained THC-COOH from the time period during which the volunteers were ingesting THC, as well as before the time they were ingesting it. Because THC-COOH is secreted by oil glands, it is likely that the metabolite contaminated the entire hair shaft. From a forensic standpoint, this is not good, as it suggests that THC-COOH can be transferred from one person to another via oil secretions. Indeed, THC-COOH has been detected in the hair of children younger than two years old. Obviously, these youngsters aren't smoking the ganja quite yet. Contamination from family members is almost certainly the correct explanation.

Obviously, this experiment needs to be repeated with a much larger sample size. But, its results cast deep suspicion on the reliability of hair tests for marijuana.

Source: Bjoern Moosmann, Nadine Roth & Volker Auwarter. "Finding cannabinoids in hair does not prove cannabis consumption." Scientific Reports 5, Article number: 14906. Published online: 07-October-2015. doi:10.1038/srep14906

(AP photo)

Fungi Found in Brains of Alzheimer's Patients

Alex B. Berezow - October 27, 2015

Despite years of intense medical research, the cause of Alzheimer's remains enigmatic. The ultimate molecular manifestation of the disease consists of the accumulation of a small toxic protein called amyloid beta that causes inflammation and destroys neurons. Why this occurs in some individuals but not others is unknown. Genetic, immunological, and environmental risk factors have been investigated, but no smoking gun has emerged.

A relatively new hypothesis is that fungal infection can trigger the disease. Back in 2014, a group of Spanish researchers found fungal DNA and proteins in the brains of Alzheimer's patients. Now, the same team has performed a new analysis using fungus-specific antibodies. They show that several different fungi are present, both inside and outside cells, throughout the brains of Alzheimer's patients. (See figure.)

In the figure above, the authors stained (in green) various regions of an Alzheimer's brain with antibodies against four fungi: Candida famata, Candida albicans, Phoma betae, and Syncephalastrum racemosum. All samples were positive. The authors then performed PCR, a test that detects DNA, on ten additional brains with Alzheimer's. All contained fungi, while control (disease-free) brains did not.

So, does this constitute "slam dunk" evidence for a fungal cause of Alzheimer's disease? Unfortunately, no. There are still many questions that need to be answered. For instance:

1. Is fungal infection a cause or consequence of Alzheimer's? It is possible, if not likely, that people with Alzheimer's disease are so sick that their brains become susceptible to fungal infection. Under this scenario, fungus would be a consequence, not a cause, of Alzheimer's.

2. Why are so many different fungi present in the brains of Alzheimer's patients? Altogether, the researchers detected 10 different types of fungus. From an infectious disease standpoint, it is unlikely that so many different fungi are acting as pathogens. While it is certainly possible that a toxic cocktail of fungi triggers Alzheimer's, this result is more suggestive of an opportunistic infection (i.e., a microbe taking advantage of an unhealthy host).

3. How do fungi cause the build-up of toxic amyloid beta proteins? This question was posed in an email to RealClearScience by epidemiologist and Alzheimer's disease expert Walter Kukull of the University of Washington. Before fungus can be declared the cause of Alzheimer's, it must be shown how it is to blame for the molecular manifestation of the disease.

4. Do antifungal agents cure or block the progression of Alzheimer's? The authors correctly note that clinical trials using antifungal agents will be necessary to test their hypothesis.

The authors, therefore, have opened a very intriguing new line of investigation for Alzheimer's researchers. However, it is still far too early to pop the cork on the champagne bottles.

Source: Diana Pisa, Ruth Alonso, Alberto Rábano, Izaskun Rodal & Luis Carrasco. "Different Brain Regions are Infected with Fungi in Alzheimer's Disease." Scientific Reports 5, Article number: 15015. Published online: 15-October-2015. doi:10.1038/srep15015

(AP photo)

Deadly Heat Projected in Persian Gulf by End of Century

Ross Pomeroy - October 26, 2015

If climate change continues unabated, the Persian Gulf will experience heat waves that push the heat index beyond 170 degrees for extended periods of time. This startling projection was just published online in the journal Nature Climate Change.

A heat index of 170 is particularly concerning because it roughly corresponds to a wet-bulb temperature of 35° Celsius. Wet-bulb temperature factors in both actual air temperature and the moisture the air contains. At 35° Celsius, the human body's cooling systems are rendered inoperable. Rather than shed heat to the environment, the body takes it in. In such a hostile environment, young and fit individuals will be at risk of hyperthermia and death, even when under the shade.

A wet-bulb temperature of 35° Celsius has never been directly observed, but residents of Bandar Mahshahr in Iran came close to experiencing it this past summer, when temperatures of 115° Fahrenheit were accompanied by a relative humidity of 49%, producing a wet-bulb temperature of 34.6 °C.

Today, temperatures like that are headline-grabbing rarities, but the architects of the new paper, Jeremy Pal and Elfatih A. B. Eltahir, respectively based out of Loyola Maramount University and the Massachusetts Institute of Technology, say such conditions could potentially become the new normal for extreme heat waves in the Persian Gulf after 2070. 

Particularly concerning, Pal and Eltahir note, are the potential ramifications for the Hajj, the Islamic pilgrimage to Mecca undertaken by millions every year.

"This necessary outdoor Muslim ritual is likely to become hazardous to human health, especially for the many elderly pilgrims, when the Hajj occurs during the boreal summer."

The Persian Gulf is uniquely susceptible to extreme heat conditions on account of its regularly clear skies, which allows solar radiation to rain down, as well as relatively shallow seas nearby, which absorb heat and release water vapor that retains heat near the ground.

Luckily, the potentially deadly conditions in the Persian Gulf predicted by Pal and Eltahir's models only occur under the "business as usual" scenario, in which no steps are taken to curb carbon emissions and average global temperatures rise by 6.7° F. If temperatures only rise by 3.2° F, then the intolerable conditions will largely be avoided, they say.

Source: Jeremy S. Pal and Elfatih A. B. Eltahir. Future temperature in southwest Asia projected to exceed a threshold for human adaptability. Nature Climate Change. PUBLISHED ONLINE: 26 OCTOBER 2015 | DOI: 10.1038/NCLIMATE2833

(Image: AP)

Start of Lightning Bolt Caught on Camera

Ross Pomeroy - October 20, 2015

You've seen lightning countless times before, but have you ever actually seen the birth of a lightning bolt? Three years ago, electrical engineers Joan Montanyà and Oscar van der Velde of the Polytechnic University of Catalunya in Barcelona, Spain set up a high-speed camera in the Ebro Valley of northeastern Spain amidst a tremendous lightning storm, and filmed the luminous carnage above in super-slow motion. Among the flurry of cloud-covered flashes and ground strikes, the duo was lucky enough to catch a rare sight on camera: a lightning bolt entirely outside of a cloud.

They revealed their footage, along with an in-depth description, last Friday in Nature's Scientific Reports.

The clip above is thirty-two seconds long, but the events it depicts lasted roughly 25 milliseconds in reality. The two squiggly white lines you see at the beginning are both charged lightning channels extending out from the clouds above. At around one second (0.09ms), a path of ionized air called a leader forms at the end of the lightning channel at the right. As it branches and extends out, it eventually comes into contact with the charged channel on the left at roughly seven seconds (6.1ms). At this point, the electrical resistance in the air breaks down and a flash of electrical energy occurs between the two channels: a lightning bolt.

While we thank Montanyà and van der Velde for the electrifying and elucidating footage, we remind them that lightning storms can be quite hazardous, and next time, it might be wiser to seek shelter.

Source: Montanyà, J. et al. The start of lightning: Evidence of bidirectional lightning initiation. Sci. Rep. 5, 15180; doi: 10.1038/srep15180 (2015).

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