Government Report Reveals Widespread Clinical Trial Fraud in China

filed under: medicine
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The Chinese pharmaceutical industry has a long and, frankly, kind of horrific history with bad science. Now, the Chinese government says a full 80 percent of drug trials awaiting approval involved “fabricated” data. The findings were published in a report by the Chinese State Food and Drug Administration (SFDA).

This is not a new problem. Quality-control issues with drug manufacturing have led to falsified data, which led to bribery and corruption, which led to the approval of dangerous products, which led to poisonings, which in turn led to the state-sanctioned execution of SFDA director Zheng Xiaoyu.

The nation’s government is hard at work trying to turn the leaky, rotting ship of the pharma industry around, but it’s slow going. In an effort to stem the tides of dirty data, the SFDA recently announced a plan to employ stricter “punishments” for industry scientists who step out of line.

They also undertook a massive investigation into all 1622 drugs awaiting SFDA approval for mass production. The results of each drug’s clinical trial were rigorously examined and analyzed for signs of doctoring, including the removal or downplaying of a drug’s negative or dangerous effects on study participants.

The report found that such practices were rampant, touching at least 80 percent of the drugs in question. Some of the data were incomplete; other parts could not be traced back to the original research; and others still simply failed to meet regulatory and scientific standards. The depth and breadth of the issues represent “… a breach of duty by supervision departments and malpractice by pharmaceutical companies, intermediary agents, and medical staff,” the agency wrote in its report. As a result, the SFDA has canceled more than 80 percent of the current drug applications.

This all may seem shocking to us, but to those on the inside, it’s hardly news. “Clinical data fabrication was an open secret even before the inspection,” said one anonymous hospital chief quoted in Radio Free Asia (RFA).

Civil rights activist Mai Ke said the problem stretches beyond Western-style drugs into Chinese traditional medicines. But “it’s not just the medicines,” Mai told RFA. “In China, everything is fake, and if there’s a profit in pharmaceuticals, then someone’s going to fake them too.”

[h/t RFA]

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October 4, 2016 – 10:30am

Scientists Develop Test-in-a-Box for Chikungunya Virus

filed under: health, medicine
Image credit: 
Ahmed Abd El Wahed

As mosquito-borne viruses like Zika, Dengue, and Chikungunya continue to spread across the globe, rapid diagnosis and treatment are more important than ever. In a recent paper published in the journal PLOS Neglected Tropical Diseases, German researchers describe an inexpensive, portable test that could help speed up Chikungunya diagnosis in remote areas.

The word “chikungunya” means “to become contorted” in the Kimakonde language of southeastern Africa, and refers to the curled-up posture of people in pain. The symptoms of Chikungunya virus (CHIKV)—joint pain, muscle pain, and fatigue—are similar to those of a bad flu and will generally resolve on their own after a few days or weeks. But they also look a lot like the initial symptoms of Dengue fever, which can be fatal unless it’s treated quickly. The two illnesses are carried by the same mosquito species, Aedes aegypti and Aedes albopictus, and are found in the same parts of the world. Identifying which of these viruses a patient has can be a matter of life and death.

Current CHIKV tests rely on polymerase chain reaction, or PCR, which chemically amplifies any traces of RNA or DNA in a sample to make them easier to identify. But PCR is time- and cost-intensive and requires refrigeration, which makes it an impractical choice in remote areas. An international team of researchers decided to see if they could do better.

They set PCR aside in favor of a technique called reverse transcriptase recombinase polymerase amplification (RT-RPA), which they hoped would also amplify the RNA of the Chikungunya virus (CHIKV). To test their assay, the team ran samples from 58 patients with suspected CHIKV infection and another 20 whose infection had been confirmed through both a PCR scan and their new RT-RPA.

The results were promising indeed. The patients’ samples had included 18 different CHIKV strains, and the RT-RPA spotted them all. The new test correctly diagnosed 36 patients, and didn’t return a single false positive. The RT-RPA was slightly less sensitive than the PCR, but it was also faster and more shelf-stable.

“The CHIKV RPA assay presented here is a promising tool for CHIKV diagnostics at the point of need,” the authors write in their paper.

Still, the test isn’t ready for primetime just yet. In its present incarnation, the assay requires a lot of steps and pipetting, and costs around $5. Ideally, the researchers say, the process would be even simpler and max out at $1. They’re continuing to refine their product, and recommend combining it with Dengue and Zika tests, which “…would improve outbreak investigations, since the three viruses induce the same clinical picture upon infection and increasingly co-circulate in many parts of the world.”
 
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September 30, 2016 – 7:30pm

#FieldWorkScares Showcases Science’s Terrifying Side

filed under: science
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It’s not all white coats and Erlenmeyer flasks. Scientists risk their shoes, their pants, and often their lives in the field in order to get the data they need. This week they’re sharing some of their worst “Oh god, I’m going to die tonight,” fieldwork moments on Twitter. 

Wildlife biologist and cartoonist Arjun Srivathsa wasn’t the only one heeding the call of the wild:

Dani Rabaiotti studies climate change and has witnessed some strange weather …

… and rude awakenings

What scares scientists the most? A few themes have begun to emerge.

There are snakes:

The field itself:

But a consensus is building: fieldwork hell is other people.

Here’s to the brave researchers putting themselves out there for science’s sake. Stay safe out there, y’all.

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September 29, 2016 – 5:30pm

Your Dog’s Interest in You Might Be Genetic

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Mia Persson

The love affair between dogs and people is an old one indeed, stretching back at least 15,000 years. Dogs are our coworkers, guides, companions, and family members. But how did they get that way? A new paper published in Scientific Reports proposes an intriguing possibility: dogs have a genetic predisposition to crave human companionship.

Previous studies have suggested a genetic component to the domestication of dogs. To further test that hypothesis, five researchers from Linköping University in Sweden assembled an enormous group of 437 laboratory-raised beagles and gave each one an impossible test. Each dog was brought to a room containing a box with three dishes, and each dish held a treat. To get the treat, the beagle needed to figure out how to slide the cover off the container. But there was a catch: one of the containers was covered with transparent Plexiglas and would not yield its treat no matter what the confused beagle did.

The dog was not alone in the testing room; each was accompanied by a seated researcher, who looked away while the dog wrestled with the puzzle box. The real test came when each dog realized it could not retrieve the last treat. At this point, some dogs gave up and started walking around the room. But others—many others—looked to or approached the researcher for help, a behavior that demonstrated their interest in people.

Each dog’s test was videotaped and its reactions coded and quantified. The researchers then identified the 95 most sociable dogs and the 95 least sociable dogs, and sequenced their genomes, looking for trends.

They found them. The most sociable dogs showed activation in two highly specific genomic regions. The presence of a single marker on the 26th chromosome of the SEZ6L gene was a significant indication that a beagle would have spent more time near and physically touching the researcher during the test. Another two markers on chromosome 26 of the ARVCF gene were strongly associated with seeking out human contact.

These genomic regions are not unique to dogs and, the researchers say, their role in socialization may not be either. Studies in humans have found a relationship between changes in SEZ6L and autism. ARVCF has been linked to schizophrenia, as have COMT and TXNRD2, which both hail from the same genetic neighborhood.

“This is, to our knowledge, the first genome-wide study presenting candidate genomic regions for dog sociability and inter-species communication,” the authors write. They acknowledge that more research is needed to validate their findings. Still, they say, “these results contribute to a greater insight into the genetic basis of dog-human communicative behaviors and sociability, increasing our understanding of the domestication process, and could potentially aid knowledge relating to human social behavioral disorders.”
 

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September 29, 2016 – 4:30pm

New Study May Explain How Zika Virus Causes Microcephaly

Dr. Stella Guerra performs physical therapy on an infant born with microcephaly at Altino Ventura Foundation on June 2, 2016 in Recife, Brazil. Image Credit: Mario Tama // Getty Images

 
One question underlies the race for a Zika vaccine: What is this virus, exactly, and how does it work? A new paper in the journal Cell Host & Microbe takes us one step closer to understanding by illuminating the relationship between Zika infection and microcephaly.

Babies with the congenital condition called microcephaly are born with unusually small heads and often have difficulties with brain development. Women who become infected with Zika virus while pregnant are at risk for transmitting the virus to their infants, who may be at higher risk for microcephaly. But just how Zika causes microcephaly has remained something of a puzzle.

To take a closer look, researchers at Stanford University cultured human stem cells in petri dishes and infected them with the virus. As the cells developed into embryos, the team was able to monitor exactly what went wrong with which cells.

Previous studies had focused on neural progenitor cells, which eventually grow into the nervous system. The Stanford team found a vital element in a second type of cell: cranial neural crest cells (CNCC). But where neural progenitor cells are easily killed off by the virus, cranial neural crest cells responded quite differently, secreting two kinds of cytokines, or inflammatory immune response signaling molecules, in reaction to the presence of the virus. That triggered the growth of more new neural cells—and sent the process of brain and skull development off the rails. Some cells split prematurely, and others died. The virus effectively interfered by confusing communication—or “crosstalk,” as the researchers describe it—between cranial neural crest cells and neural progenitor cells.

“Our results suggest that CNCC infection by ZIKV may contribute to associated embryopathies through signaling crosstalk between developing face and brain structures,” they write.

Co-senior author Joanna Wysocka is a chemical and systems biologist at the Stanford University School of Medicine. She says it’s possible that the virus is affecting still other cell types in addition to these two.

“Neural crest cells are one example,” she said in a press statement, “but such mechanisms may also be relevant to other tissues that come in contact with the developing brain during head formation and could be infected by Zika virus.”

Wysocka emphasized that microcephaly is a congenital issue and not a risk for adults who contract the virus.

The team’s findings are “remarkable,” physician Larry Brilliant tells mental_floss. (Brilliant was unaffiliated with the study.) The notion of crosstalk between the cell types is “phenomenally important,” he said, because “they lead to questions of [whether] therapeutic interventions might be possible even after the virus is transmitted.”

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September 29, 2016 – 12:01pm

Scientists Bioengineer Arteries That Could Potentially Grow Inside the Body

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University of Minnesota

Welcome to the future. Scientists have created arteries that can be safely implanted and continue growing in their hosts. They published a report of their progress today, September 28, in the journal Nature Communications.

Transplanted organs and tissue face several major obstacles to success. First, there’s ensuring the transplant is right and safe for the recipient. Then there’s the possibility that the recipient’s body will reject the new part. Finally, there’s the need for the implanted materials to cooperate with the cells around them, to grow and work together. Scientists have made major headway on the first two issues over the last few decades. But when it comes to coaxing transplanted parts to grow, we’re really just getting started.

Growth is especially important—and hard to produce—in blood vessel transplants. Scientists have found ways to make it happen, but they involve growing new vessels in the lab from scratch, using each patient’s own cells. The customization process is expensive and time-intensive, which seriously limits its use.

So a team of researchers at the University of Minnesota set out to find another way. They essentially wanted to build a generic or base model of the pulmonary artery—one that could be kept on hand in a hospital and used as needed.

They started with sheep. The team took samples of sheep skin cells and mixed them with a clotting agent and calcium chloride to give them rigidity, then pumped them into a tube-shaped glass mold. As the cells took shape in the tubes, the researchers infused them with nutrient fluids to give them the shape and flexibility they would need. They then transferred the cells to a bioreactor for another five weeks of maturation and stretching.

Once the arteries had grown and stretched to the right size, the team rinsed them in chemicals that stripped out all the original skin cells, a process known as decellularization. All that remained were the newly grown structures themselves; the shapes of blood vessels, with none of the immune system–triggering cells.

The new arteries were then implanted in three 8-week-old lambs. The lambs were patched up, then monitored with regular ultrasound scans 8 weeks, 30 weeks, and 50 weeks after their surgery. After the last scan, the lambs were euthanized and their arteries removed and dissected.

The artificial blood vessels had fared incredibly well. Not only did the lambs’ bodies not reject the grafts, but they seemed to embrace them. The transplanted arteries entered the lambs’ bodies as scaffolds, essentially, yet by the time the animals reached young adulthood the scaffolds were filled and composed of their own cells. The blood vessels grew with their owners, serving them well.

Jeffrey Harold Lawson is a professor of vascular surgery at Duke University. “This appears to be very exciting work and continues to support the emerging field of vascular tissue engineering,” Lawson, who was unaffiliated with the study, told mental_floss. “It is very exciting to see the vessels grow over time with the sheep and repopulate with the hosts’ own cells. If work like this continues to make both preclinical and clinical progress, it could revolutionize the field of pediatric cardiac surgery and potentially avoid reoperative procedures for thousands of young children.”

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September 28, 2016 – 11:15am

What Long-Dead Bees Can Tell Us About Our Ancestors

Image credit: 
Parker et al (2016)

To the dedicated detective, everything looks like a clue. Take this approximately 3-million-year-old bees’ nest, for example: Researchers say its very presence speaks volumes about the world in which our early ancestors lived. They published their report today, September 28, in the journal PLOS One.

The ancestor in question is Australopithecus africanus, a small hominid species with both human- and ape-like features that lived in modern-day South Africa. Au. africanus was little to begin with—adult males averaged around 4’6”, females 3’9”—but the first specimen ever found was littler yet. The Taung child, as it came to be known, was first unearthed in 1924, and represented the earliest human ancestor ever found in Africa. Archaeologists found a few more Au. africanus individuals over the next decade, and then the wellspring of remains dried up. We haven’t found any more Australopithecus there since.

But the absence of bodies isn’t the same thing as a dead end. Researchers have simply turned their attention to exploring the world of Australopithecus in other ways: namely, looking at the site itself, at its geology, environment, and all the other fossils found there.

When we think about fossils, we typically think about the remains of plants and animals. But the traces left behind by these organisms can become fossils too. These footprints, burrows, and nests are harder to pin down to a single species, so scientists classify them into groups called ichnogenera.

Fossilized burrows in the ichnogenus Celliforma were most likely made by prehistoric bees. Unlike the humming, social hives of honeybees, each flask-shaped Celliforma nest was dug out of the ground and occupied by a single bee.

These nests are somewhat rare, and they’ve never been seen before in Africa, so researchers were understandably pretty psyched when they found one in Au. africanus territory near the edge of the Kalahari desert.

The nest was in great shape, given its age. The outside was covered with 25 small chambers, each of which would have housed a baby bee millions of years ago. Computed tomography (CT) scans of the entire nest revealed a complex system of tunnels and cells within, as well as traces of tiny plant parts that would have once lined its walls.

Parker et al. (2016)

The researchers say the nest’s overall structure is most similar to the homes of modern carder bees, which glaze the interior of their nests with a thin layer of clay, smooth it out with a wax-like substance, then add pieces of plants.

The nest’s structure and contents suggest that it was built in light, dry soil—findings that support previous studies, which hypothesized that Au. africanus may have lived in an arid, savannah-like environment.

“Insect traces are rarely considered in detail,” the study authors conclude, “yet they could offer important palaeoenvironmental insights, with the potential to reveal valuable information about hominin palaeoecology.”

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September 28, 2016 – 11:01am

Whaling Voyages Also Devastated Walruses and Many Other Animals

Image credit: 
Angsar Walk via Wikimedia Commons // CC BY-SA 3.0

The 19th century was a heady time for American whalers, and, consequently, a pretty awful time for whales around the world. But cetaceans weren’t the only ones to take a hit. A forthcoming study of whaler ship logs found that thousands of other animals, from walruses to kangaroos, all fell prey to whalers’ weapons.

The study itself began as a midterm project for undergraduates in Joshua Drew’s Historical Ecology class at Columbia University. Drew wanted to give his students something other than lectures, he tells mental_floss, and thought he might be able to help prepare them for academic life after college. “There’s this idea that when you get accepted to a graduate program somebody bops you on the head with a magic wand,” he says, “and suddenly you know how to write papers.” (Spoiler: “That’s not the case.”)

Drew knew that Massachusetts’ New Bedford Whaling Museum had scanned and digitized dozens of logbooks taken from whaling ships. “It was a great dataset, just sitting there,” Drew says. He set his class a task: Identify and add up all the non-whale animal kills recorded in each of 79 logs from 1846 to 1901.

This was slightly harder than it sounds. The whalers who kept the logs were, well, whalers, not scientists. Different people used different names to refer to the same animal, and sometimes lumped several species together.

And then there was the handwriting—beautiful to look at, but a huge pain to decipher. “Ugh,” Drew remembers. “It was like Elvish script.”

But the students loved it. After the midterm, they asked if they could keep going, and Drew decided to extend the project for the rest of the semester. Drew and his seven students conducted a formal study from start to finish, beginning with recording and classifying every single animal’s death from the scanned primary source documents.

The students analyzed the data and compared their findings with climate data and merchants’ records. The last two weeks of class were dedicated to writing and preparing the study for publication. On the final exam, each student had to draft the paper’s abstract. “By this point in the project, they definitely should have known enough about it to write one,” Drew said. “Plus, I hate writing abstracts. I figured I’d give them the pleasure instead.”

The resulting paper—soon to be published in the journal Ecology and Evolution—is full of surprises. As expected, non-whale animal deaths were widespread, but they were also astonishingly diverse. “There were tons—literally, tons—of walruses being caught,” Drew says. There were seals and cod and caribou, otters and ptarmigans. More than 150 rabbits. Seventeen polar bears. Seven bears. Four beavers. Two kangaroos. The whalers had been busy.

Terse and no-nonsense though the logbooks might have been, they managed to create a vivid picture of life at sea. Gaps of time between entries suggest “days and days of boredom punctuated by life-threatening exhilaration,” Drew says. The men aboard these ships were hungry for action, for a payday, and for something other than the disgusting preserved food in the hold. When an opportunity to go ashore and hunt arose, they were going to take it.

These were desperate and dangerous days, and not just for the whalers’ quarry. “The logs talked about people being killed or getting incredibly sick,” Drew says, “and they were just trapped on these boats in the middle of the ocean.” He says the lists of kills are, in their own way, tinged with a sense of loneliness.

This is the power of historical ecology, Drew says: to show us how we got here, for better or for worse. He says, “It’s like lifting that veil and seeing this wonderful complexity, this drama and dance, that led to the world being the way it is now.”

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September 27, 2016 – 10:30am

What Are Those Tiny Spots on Apples?

The little pinprick spots on apples, pears, and potatoes are called lenticels (LEN-tih-sells), and they’re very important.

Plants need a constant stream of fresh air, just like people, and that “fresh air” means carbon dioxide. Flowers, trees, and fruit all take in carbon dioxide and give off oxygen. But unlike people, plants don’t have nostrils.

That’s where a plant’s lenticels come in. Each little speck is an opening in the fruit or tuber’s skin or the tree’s bark. Carbon dioxide goes in, and oxygen comes out. Through these minuscule snorkels, a plant is able to “breathe.”


Like any opening, lenticels are vulnerable to infection and sickness. In an apple disease called lenticel breakdown, a nutrient deficiency causes the apples’ spots to darken and turn into brown pits. This doesn’t hurt the inside of the fruit, but it does make the apple look pretty unattractive. In the equally appealing “lenticel blotch pit,” the skin around the apple’s lenticels gets patchy and dark, like a weird rash. 


September 24, 2016 – 11:01pm

DNA of Ancient Cats Traces the Path of Their Global Conquest

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iStock

A new study of ancient DNA presented at the 7th International Symposium on Biomolecular Archaeology has revealed the secret story of cats’ spread across the globe.

Cats are mysterious creatures. They’re independent yet social, aloof yet endearing, and very good at getting what they want. Like any organism, the very first cats originated in one place, then spread. They spread, and spread, and continue to spread, becoming beloved pets and conservationists’ worst nightmare, often at the same time.

Exactly how they managed this feat of feline world domination has remained something of a puzzle. How did these small, terrestrial animals make it across the oceans? Cats have no value as livestock (like cows) or transport (like horses). They’re good workers as mousers, but only when they want to be. And we talk about the “domestic” cat, but some scientists think that may be a misnomer—maybe we haven’t really domesticated them at all.

But they may have domesticated us. Look back 12,000 years in time to the Fertile Crescent at the dawn of agriculture, when cats were buried along with people. Look to the millions of sacred cats mummified in ancient Egypt. Every time we find the carefully entombed remains of a cat, we find a clue to how they got to be who (and where) they are today.

Researchers lead by Eva-Maria Geigl, an evolutionary geneticist at the Institut Jacques Monod in Paris, sequenced DNA taken from the remains of 209 cats found at more than 30 archaeological digs across Africa, the Middle East, and Europe. They focused exclusively on mitochondrial DNA, which is inherited maternally. The samples represented an enormous swath of history, from our days as hunter-gatherers up through the 18th century.

The cats’ DNA painted a picture of two distinct bursts of kitty scattering (s-cat-tering, if you will). The first was in the Middle East, where farming began about 10,000 years ago. As farming communities grew out toward the Mediterranean Sea, the cats came with them. The study authors say the farms’ piles of grain likely attracted rodents, which then brought out the wild cats. And once farmers saw the value of having fierce mousers around, they likely tried to find a way to keep them.

Fast-forward several millennia to the second wave, when noble Egyptian cats began to sow their wild oats throughout Eurasia and Africa. A family line found in Egyptian mummy cats from the end of the fourth century BCE to the fourth century CE was also found in cats from Bulgaria, Turkey, and sub-Saharan Africa during roughly the same time.

Then they hit up the Vikings. Seafaring life is a tangle of dangers and threats, including the voracious mouths of rats and mice in a hold full of essential provisions. By around the 8th century, Vikings, too, had seen the value of keeping cats around, as evidenced by feline remains found in Viking settlements.

And still they spread. Cats are something of a contentious topic these days. The hunting skills that made them so attractive to our distant ancestors can today make them a serious threat to wildlife. Some places have banned cats altogether, although it might already be too late—they’ve already got us thoroughly wrapped around their little paws.

[h/t Nature]

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September 23, 2016 – 3:15pm