Friday, August 30, 2013

A Bit of Brain Trivia

Simulating 1 second of real brain activity takes 40 minutes and 83K processors — Tech News and Analysis

by Derrick Harris,

August 2nd 2013

A team of Japanese and German researchers have carried out the largest-ever simulation of neural activity in the human brain, and the numbers are both amazing and humbling.

The hardware necessary to simulate the activity of 1.73 billion nerve cells connected by 10.4 trillion synapses (just 1 percent of a brain’s total neural network) for 1 biological second: 82,944 processors on the K supercomputer and 1 petabyte of memory (24 bytes per synapse). That 1 second of biological time took 40 minutes, on one of the world’s most-powerful systems, to compute.

If computing time scales linearly with the size of the network (a big if; I have no idea if this would be the case), it would take nearly two and half days to simulate 1 second of activity for an entire brain.

Still, the researchers are excited by what they’ve accomplished. According to a quote from project leader Markus Diesmann in the press release announcing the simulation: “If peta-scale computers like the K computer are capable of representing 1% of the network of a human brain today, then we know that simulating the whole brain at the level of the individual nerve cell and its synapses will be possible with exa-scale computers hopefully available within the next decade.”

Although they’re measured in FLOPS — floating point operations per second — rather than bytes, the prefixes measuring supercomputer performance are the same as those measuring data storage. A system operating at 1 exaflop would be 1,000 times more powerful than a system operating at 1 petaflop. K — now the world’s fourth fastest supercomputer — is capable of 10.51 petaflops.

Importantly, though, the recent simulation was merely a test of the open source NEST simulation software the researchers have been developing. Research into specific diseases, and projects such as Europe’s Human Brain Project and the United States’ BRAIN initiative, will require more job-specific tuning.

Figuring out the mysteries of the human brain isn’t just a matter of sheer scale and advanced software, though. As GigaOM’s Stacey Higginbotham has reported, numerous companies and institutions, including IBM, are working on projects to better our understanding of the brain. Some are even developing chips designed to mimic it — albeit on a much smaller scale.

This article was updated at 11:34 p.m. on Aug. 3 to correct the amount of memory allocated per synapse to 24 bytes.

Tuesday, August 27, 2013

Step two of home health checks

Home Heart-Health Checks Work, but Follow-Up Is Still a Must


August 5th 2013 6:43 AM

More doctors are looking to a host of emerging gadgets patients can use to manage chronic disease at home, such as do-it-yourself blood pressure monitors.

But, making use of the reams of data they can produce remains a problem. A new study shows that patients who monitor their blood pressure at home don't get much benefit—unless their doctors provide extra services like digital monitoring and counseling.

It is a dilemma for digital medicine. As technology bridges patients and doctors across geographies and gathers ever-richer health data, efforts to translate those gains into everyday practice often lag behind. Doctors often aren't paid for such services, and extra resources needed—like extra staff—to act on data aren't always available. "Many practices aren't yet fully prepared for the onslaught of data when patients are really online and providing a lot of monitoring data," said Jorge Plutzky, a cardiologist at Brigham and Women's Hospital in Boston, who wasn't involved in the study.The analysis published Monday in the Annals of Internal Medicine found that patients who got such extra support coupled with home blood-pressure monitoring saw significant benefits after a year, while it wasn't clear home monitoring without added medical practice infrastructure helped much at all in the long term.

While home monitoring for conditions such as diabetes has been a staple of disease management, increasingly sophisticated devices are able to channel information about serious ailments directly to doctors. Wireless scales catch changes in weight that can be symptoms of worsening heart failure, home monitors track heart-rhythm disorders for patients with defibrillators and pacemakers, and a new generation of blood pressure cuffs can seamlessly link patients with high blood pressure to clinics.

Controlling blood pressure is key to reducing patients' risks for heart attacks and strokes. Even temporary spells of high blood pressure, known as hypertension, are thought to increase such risks. One-third of adult Americans—more than 76 million—have hypertension, or blood pressure of 140/90 mm Hg or higher, according to the Centers for Disease Control and Prevention. Drugs, diet and exercise leave only half of those patients with well-controlled blood pressure.

Blood pressure is hard to pin down. It fluctuates throughout the day, and many patients believe it rises when they visit the doctor. Conversely, measurements taken at office visits every few months can be inaccurate and may suggest blood pressure is controlled even when it is soaring at other times.

Some doctors are looking to technology as a solution. In April, Diego Remolina, an internal-medicine doctor at Central de Salud Esperanza, a Chicago clinic, asked a patient, Maria de Lourdes Segura, a 46-year-old homemaker, to start monitoring blood pressure at home with a new machine that transmits data to the clinic, hoping to help control her hypertension and diabetes.

The patient said her hypertension was tied to anxiety due to office visits, and an older home monitor that didn't connect to the clinic seemed to have a wide range of readings that gave Dr. Remolina more questions than answers. With the new system, provided by a local group called the Medical Home Network, Dr. Remolina was "able to tell her with confidence that she needed a different approach to her high blood pressure treatment," he said. Dr. Remolina, who prescribed a third blood-pressure drug, said he had been reluctant to add the medicine earlier because of the risk of side effects.

The new approach works for Ms. Segura, too. "You really start thinking more about all of it"—taking medicine on time, adhering to a healthier diet and exercising—"when you know the doctor is interested in looking at" the readings, Ms. Segura said, speaking in Spanish, through a translator.

In the Annals' analysis, studies of patients given home testing, but no extra help other than ordinary physicians' visits, saw modest declines in their blood pressure after six months, but the improvement vanished after a year. Experts said they believe the temporary improvement was tied to better patient adherence to medication regimens, at least at first.

Studies in which patients used home monitors along with web-based connections to their clinics, counseling or other services, seemed to produce a more lasting benefit. In the most robust studies, patient's systolic pressure improved by 3.4 points to 8.9 points after a year, compared with usual care. The Annals' study, a systematic review 52 previous clinical studies through February, was funded by the federal Agency for Healthcare Research and Quality.

The study shows home blood-pressure monitoring can be useful, said Katrin Uhlig, a nephrologist at Tufts Medical Center in Boston and the lead author of the analysis. But, to see major benefits, "you would actually need the additional staff. You would need the infrastructure for transmission of values and have systems in place to act on readings in a responsible way," Dr. Uhlig said.

The other deterrent is technology, Dr. Magid said. When he first studied home monitoring about five years ago, his research team had to push patients to write down measurements, and either report them over the phone or fax notes to researchers. That study showed only a modest improvement. But, in a study published earlier this year in the journal Circulation, Dr. Magid's team used a new system that automatically sent blood-pressure data to a team of pharmacists, who could recommend changes to medication regimens. The results were much stronger, with patients at 10 Kaiser clinics seeing systolic pressure decline by an average of 12 points more than a group that received usual treatment over six months. The research was funded by the American Heart Association
Few physicians have such systems now, in part because insurers tend not to pay for care unless patients physically show up for office visits, said David Magid, a Colorado-based researcher for Kaiser Permanente, the managed-care organization. "There is a financial disincentive for doctors when patients do home blood-pressure monitoring," he said.

While a new array of home monitors have features such as blue-tooth connectivity or companion iPhone apps, the basics still work for most patients, said Tracy Stevens, a heart association spokeswoman and cardiologist at St. Luke's Health System in Kansas City, Mo. "You can get a fabulous blood pressure cuff that's accurate, easy to use and fully automatic for $50," Dr. Stevens said. More sophisticated home-use models range to as much as $300.

For patients who want to use home monitoring, but don't have access to a medical practice with the infrastructure to run a sophisticated monitoring program, Dr. Stevens suggests a low-tech solution. "Have a little spiral notebook dedicated for your blood pressure. Write down the dates, times and your measurements, and show it to your doctor," she said.

Write to Christopher Weaver at

A version of this article appeared August 6, 2013, on page D1 in the U.S. edition of The Wall Street Journal, with the headline: Doctor's Order: Test at Home But Don't Forget to Call.

Monday, August 26, 2013

blood-sucking robot could treat hard-to-reach brain hemorrhages.


Wow of the week: Blood-sucking robot could save one in 50 of us who will develop brain clot

by Lindsey Alexander, medcitynews.comAugust 10th 2013 8:59 AM

Fear not–this blood-sucking robot could treat hard-to-reach brain hemorrhages.

While most surgeons won’t go near a brain clot unless it’s easy to get to (read: on the surface) in fear of further damaging brain tissue, more than 40 percent of patients who have them die within a month.

The active cannula, what Vanderbilt assistant professors Robert J. Webster III and Kyle Weaver call the image-guided surgical device, uses steerable needles to penetrate the brain and suck away those riskier clots.

Webster’s father had a brain hemorrhage, and had been working on a transnasal surgical device. But not just patients and families have dreamed of such a device, of course. Neurosurgeon Marc Simard listed such a then-imaginary device as the active cannula at a conference last year, and Webster was in the audience. He realized he could morph his research to fit Simard’s description almost perfectly. Since then, the team at Vandy has moved quickly.

In simulations, the active cannula had a 92 percent success rate.

According to the press release:

The brain-clot system only needs two tubes: a straight outer tube and a curved inner tube. Both are less than one twentieth of an inch in diameter. When a CT scan has determined the location of the blood clot, the surgeon determines the best point on the skull and the proper insertion angle for the probe. The angle is dialed into a fixture, called a trajectory stem, which is attached to the skull immediately above a small hole that has been drilled to enable the needle to pass into the patient’s brain.

The surgeon positions the robot so it can insert the straight outer tube through the trajectory stem and into the brain. He also selects the small inner tube with the curvature that best matches the size and shape of the clot, attaches a suction pump to its external end and places it in the outer tube.

Guided by the CT scan, the robot inserts the outer tube into the brain until it reaches the outer surface of the clot. Then it extends the curved, inner tube into the clot’s interior. The pump is turned on and the tube begins acting like a tiny vacuum cleaner. . . .

Then it’s rotated out and extracts the tubes.

Eventually, the researchers want to make the model even more accurate. To do that they plan to “add ultrasound imaging combined with a computer model of how brain tissue deforms to ensure that all of the desired clot material can be removed safely and effectively.”

Copyright 2013 MedCity News. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.

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Thursday, August 22, 2013

Apple Inc. has asked assembler Hon Hai Precision Industry Co. to begin shipping both a new high-end and low-end iPhone in early September


Apple Inc. has asked assembler Hon Hai Precision Industry Co. to begin shipping both a new high-end and low-end iPhone in early September, people familiar with the matter said.

The shipping plans suggest consumers could soon have access to two new iPhone models, pointing to a strategy shift as Apple attempts to regain its momentum in the smartphone market. The company hasn't previously announced different iPhone models around the same time.

Apple's suppliers in Asia started mass-producing components in June for both a standard iPhone, featuring a metal casing, and a lower-cost version, people who work at those companies said.

An Apple spokeswoman declined to comment.

The Cupertino, Calilf., company has been unveiling new iPhones in the fall since 2011. It is planning a launch event on Sept. 10, according to AllThingsD, a news outlet that, like The Wall Street Journal, is owned by News Corp. It isn't clear whether Apple would launch both iPhones the same day or initially choose to showcase just one device.

New iPhones in the past have become available about a week and a half after their unveiling.

Competitors are planning to ramp up pressure by launching new products of their own around the same time.

Samsung Electronics Co., the largest smartphone maker in the world by shipments, is planning an event on Sept. 4, during which it plans to launch a new large-screen Galaxy Note phablet—or mobile device that has functions of a phone and a tablet—and a smartwatch called Galaxy Gear, people familiar with the matter have said.

Apple has been facing tough competition from Samsung and other firms making smartphones based on Google Inc.'s Android software. A perception that Apple's pace of innovation has slowed, along with some uncharacteristic missteps by the company, helped push its shares down more than 40% in the span of six months from all-time highs of more than $700 in September. The company's shares have since rebounded to above $500.

On Monday, Apple shares closed at $507.74, up 1.1%.

In years past, Apple saw spectacular expansion, with quarterly smartphone unit shipments increasing by more than 50% from a year earlier throughout the company's fiscal 2010 and in all but one quarter in 2011 and 2012. This year, however, the company has struggled to maintain that momentum; shipments rose 7% in the quarter ended in March, though they rose 20% in the period ended in June.

Apple's struggles have led to concerns among analysts that the smartphone market may be slowing, particularly in Western markets.

Even Samsung's stock has come under pressure, hurt by concerns about sales of its high-end Galaxy S4 smartphone and an announcement in July that its operating profit would be lower than expected. HTC Corp., meanwhile, has seen profits fall dramatically and BlackBerry Ltd., once a powerhouse in the industry, has put itself up for sale.

In April, The Wall Street Journal reported that Apple was working with its manufacturing partners in Asia on a less-expensive iPhone that would likely use a nonmetal casing to differentiate itself from the aluminum casing of the high-end iPhone. The shells of both iPhone models would likely come in multiple color options, officials at suppliers said at the time.

Analysts say a low-cost iPhone could help to boost Apple's sales, particularly in emerging countries such as China and India.

The company appears to be moving to capitalize on that theory, as people familiar with the matter said component orders in the current quarter for the low-cost iPhone are much higher than those for the high-end iPhone. But they said component orders for the high-end metal-case iPhone would go up in the fourth quarter.

Some market watchers are optimistic about prospects for the lower-price iPhone.

Ming-Chi Kuo, an analyst for KGI Securities in Taiwan, estimates that more than 5.2 million units of the next-generation high-end iPhone and nearly 8.5 million low-cost iPhones will be shipped during the third quarter. But by the fourth quarter, he predicts Apple will ship 28 million high-end iPhones and 18.7 million low-cost ones. All told, the analyst estimates that total iPhone shipments will top 35 million units in the third quarter—a 30% increase over the same time last year—and rise to 55 million in the fourth quarter.

People familiar with the matter in April said the new iPhone will be the same size and have the same screen resolution as the current iPhone 5.

Write to Lorraine Luk at and Ian Sherr at


Researchers Turn Off Down Syndrome Genes

Researchers Turn Off Down Syndrome Genes

by Nature and Beth Mole,

July 17th 2013

The insertion of one gene can muzzle the extra copy of chromosome 21 that causes Down’s syndrome, according to a studypublished today in Nature. The method could help researchers to identify the cellular pathways behind the disorder's symptoms, and to design targeted treatments.

“It’s a strategy that can be applied in multiple ways, and I think can be useful right now,” says Jeanne Lawrence, a cell biologist at the University of Massachusetts Medical School in Worcester, and the lead author of the study.

Lawrence and her team devised an approach to mimic the natural process that silences one of the two X chromosomes carried by all female mammals. Both chromosomes contain a gene called XIST (the X-inactivation gene), which, when activated, produces an RNA molecule that coats the surface of a chromosome like a blanket, blocking other genes from being expressed. In female mammals, one copy of the XIST gene is activated — silencing the X chromosome on which it resides.

Lawrence’s team spliced the XIST gene into one of the three copies of chromosome 21 in cells from a person with Down’s syndrome. The team also inserted a genetic 'switch' that allowed them to turn on XIST by dosing the cells with the antibiotic doxycycline. Doing so dampened expression of individual genes along chromosome 21 that are thought to contribute to the pervasive developmental problems that comprise Down's syndrome.

First steps

The experiment used induced pluripotent stem cells, which can develop into many different types of mature cells, so the researchers hope that one day they will be able to study the effects of Down’s syndrome in different organs and tissue types. That work could lead to treatments that address degenerative symptoms of Down’s syndrome, such as the tendency of people with the disorder to develop early dementia.

“The idea of shutting off a whole chromosome is extremely interesting” in Down’s syndrome research, says stem-cell researcher Nissim Benvenisty of Hebrew University in Jerusalem. He anticipates future studies that split altered cells into two batches — one with the extra chromosome 21 turned on, and one with it off — to compare how they function and respond to treatments.

Researchers have previously removed the extra chromosome in cells from people with Down’s syndrome using a different type of genetic modification. That technique relied on the fact that induced pluripotent stem cells that carry the third copy of chromosome 21 occasionally boot it out naturally — but "it’s a pain in the neck”, says Mitchell Weiss, a stem-cell researcher at the Children’s Hospital of Philadelphia in Pennsylvania. “You can’t control it.”

However, Weiss says that the latest method has its own drawbacks: turning on XIST may not block all gene expression in the extra chromosome, and that could muddle experimental results.

Still, Weiss thinks that the approach could yield fresh treatments for Down's syndrome — and prove useful for studying other chromosome disorders such as Patau syndrome, a developmental disorder caused by a third copy of chromosome 13.

This article is reproduced with permission from the magazine Nature. The article was first published on July 17, 2013.


Monday, August 19, 2013

The Quest for Better Pain Relief


The Quest for Better Pain Relief


July 29th 2013 6:51 AM

Scientists searching for better painkillers are taking inspiration from an unusual population: people who feel no pain at all.

Research has shown that rare mutations in a gene called SCN9A can give people complete immunity to pain. Now, pharmaceutical companies are aiming to develop drugs to mimic that genetic mutation.

Scientists have struggled to find better treatments for chronic pain, which affects about 1 in 5 people. Anti-inflammatory drugs such as ibuprofen and naproxen sometimes don't work very well, while more powerful opiates such as morphine, codeine or oxycodone can be dangerously addictive. People suffering from neuropathic pain tied to nerve damage, meanwhile, often get little relief from current painkillers.

Now Pfizer Inc. and a handful of smaller companies such as Canada's Xenon Pharmaceuticals Inc. and the U.K.'s Convergence Pharmaceuticals Ltd. are working on new methods tied to the SCN9A gene. Instead of muting pain by reducing inflammation, as ibuprofen and similar drugs do, or by switching on the body's own analgesic properties, as opiates do, the new experimental drugs seek to block the ability of nerve cells to send pain signals.

Nerve cells send these signals with the help of a certain type of protein, called a sodium channel, that forms a pore in the cell's membrane. Inherited mutations in the SCN9A gene block the functioning of these sodium channels, called Nav1.7 sodium channels. The experimental drugs also seek to block them—or at least to blunt their ability to transmit pain.

Because pain serves a useful biological function—it keeps us from burning ourselves, or breaking bones—complete congenital insensitivity to pain is actually a big problem. Children born with the rare pain-free syndrome need to be taught to abstain from the kind of dangerous behavior that a quick twinge of discomfort tells the rest of us to avoid.

Scientists linked the pain-free condition to SCN9A mutations in 2006, after studying several families in northern Pakistan afflicted with the syndrome, including a 10-year-old boy who worked as a street performer, entertaining crowds by walking on hot coals and forcing knives through his arms.

"Even as babies they had shown no evidence of pain appreciation," the researchers wrote of the families in a paper in the journal Nature. "None knew what pain felt like, although the older individuals realized what actions should elicit pain."

All subjects had injuries to their lips or tongues, caused by biting themselves as young children, and many had suffered frequent bruises, cuts or fractures.

Because the individuals were otherwise healthy, the researchers concluded that drugs that mimic their genetic mutation, by blocking Nav1.7 function, "have the potential to produce new and potentially safer analgesia."

Inspired by this sort of research, Pfizer and a biotech company it later acquired developed a drug that blocks Nav1.7 sodium channels, and decided that the best initial test of it was in patients with erythromelalgia—another rare genetic disease that is the mirror opposite of the pain-free syndrome.

People with erythromelalgia, also known as Man on Fire Syndrome, experience extreme sensitivity to pain. In these patients, a different type of mutation to the SCN9A gene causes Nav1.7 sodium channels to go haywire, resulting in hyperactive pain signaling.

"These people experience searing, scalding, burning pain in response to mild warmth. They describe it as feeling as if hot lava had been poured into their bodies," says Stephen Waxman, a neurologist and expert on rare pain disorders at Yale University and the Veterans Affairs Connecticut Healthcare System who has collaborated with Pfizer. Erythromelalgia often strikes the hands and feet, so sufferers spend a lot of time soaking their limbs in cold water, Dr. Waxman says. Most wear sandals, even in winter, because it keeps them cool.

Erythromelalgia is so rare that Pfizer has located just a handful of families in the U.S. to participate in the trial, says Ruth McKernan, chief scientific officer at a Pfizer unit in Cambridge, U.K., that focuses on pain.

To test the efficacy of the drug, the clinicians first trigger a pain attack in the patients by putting a warm blanket around their legs, she says. After the pain sets in, patients are given either the drug or a placebo and their pain levels are assessed. The blanket test is repeated several times over a 24-hour period. Pfizer hopes to have results of the trial by year-end.

Erythromelalgia is one, rare type of neuropathic pain, which results from nerve damage or dysfunction that is most often caused by injuries, infections or metabolic disorders such as diabetes.

Neuropathic pain affects about 8% of the population, and less than half of patients get satisfactory pain relief from current treatments, says David Bennett, a neurologist and pain expert at Oxford University in the U.K. Aside from anti-inflammatory drugs and opiates, drugs originally developed to treat epilepsy and depression also are used for neuropathic pain, with mixed success.

If the results of Pfizer's erythromelalgia study are successful, the company hopes to test the drug in other types of neuropathic pain, and possibly in pain associated with inflammation, Dr. McKernan says.

British Columbia-based Xenon Pharmaceuticals, working with partner Teva Pharmaceutical Industries Ltd. of Israel, also has tested a Nav1.7-blocking drug against a placebo pill in erythromelalgia. In the journal Pain last year, the companies reported that the drug "significantly reduced the amount of pain" in the four patients in the study. A second study of the drug's efficacy against post-dental-surgery pain also showed "encouraging" results, the partners say, though they haven't yet published the results in a medical journal.

While the efficacy of Nav1.7-blocking drugs is still far from clear, one possible benefit is their potential to be non-addictive, says Simon Tate, chief scientific officer of Convergence Pharmaceuticals, which is developing its own drug that blocks Nav1.7 sodium channels. Other types of drugs on the market today for epilepsy and other diseases block several sodium channels, including Nav1.7, and show "no evidence of addiction," he says.

Write to Jeanne Whalen at

Sunday, August 18, 2013

'Big leap' towards curing blindness in stem cell study


'Big leap' towards curing blindness in stem cell study

Jul 21st 2013

The prospect of reversing blindness has made a significant leap, according to scientists in the UK.

An animal study in the journal Nature Biotechnology showed the part of the eye which actually detects light can be repaired using stem cells.

The team at Moorfields Eye Hospital and University College London say human trials are now, for the first time, a realistic prospect.

Experts described it as a "significant breakthrough" and "huge leap" forward.

Photoreceptors are the cells in the retina which react to light and convert it into an electrical signal which can be sent to the brain.

However, these cells can die off in some causes of blindness such as Stargardt's disease and age-related macular degeneration.

There are already trials in people to use stem cells to replace the "support" cells in the eye which keep the photoreceptors alive.

Blind mice

Now the London-based team have shown it is possible to replace the light-sensing cells themselves, raising the prospect of reversing blindness.

They have used a new technique for building retinas in the laboratory. It was used to collect thousands of stem cells, which were primed to transform into photoreceptors, and injected them into the eyes of blind mice.

The study showed that these cells could hook up with the existing architecture of the eye and begin to function.

However, the effectiveness is still low. Only about 1,000 cells out of a transplant of 200,000 actually hooked up with the rest of the eye.

Lead researcher Prof Robin Ali told the BBC News website: "This is a real proof of concept that photoreceptors can be transplanted from an embryonic stem cells source and it give us a route map to now do this in humans.

"That's why we're so excited, five years is a now a realistic aim for starting a clinical trial."

Rods, blue, and cones, blue-green, detect light and create electrical signals which are sent to the brain.

The eye is one of the most advanced fields for stem cell research.

It is relatively simple as the light sensing cells only have to pass their electrical message on to one more cell in order to get their message to the brain, unlike an attempt to reverse dementia which would require cells to hook up with far more cells all across the brain.

The immune system is also very weak in the eye so there is a low chance of the transplant being rejected. A few cells can also make a big difference in the eye. Tens of thousands of stem cells in the eye could improve vision, but that number of stem cells would not regenerate a much larger organ such as a failing liver.

Prof Chris Mason, from University College London, told the BBC: "I think they have made a major step forward here, but the efficiency is still too low for clinical uses.

"At the moment the numbers of tiny and it will take quite a bit of work to get the numbers up and then the next question is 'Can you do it in man?'

"But I think it is a significant breakthrough which may lead to cell therapies and will give a much expanded knowledge on how to cure blindness."

Dr Marcelo Rivolta, from the University of Sheffield, said the study was a "huge leap" forward for treating blindness and could have implications across stem cell research.


Saturday, August 17, 2013

Device Trains Blind People To 'See' By Listening


Device Trains Blind People To 'See' By Listening

by Joey Carmichael,

Seeing without sight

Researchers have found that newly blind people can learn to "see" with their ears. The key: technology called sensory substitution devices (SSDs) that can convert visual stimuli into aural representations of the surroundings, allowing users to reacquire lost abilities; a blind man who drops his keys might be able to locate them.

The devices could eventually duplicate "the phenomenological experience of vision" in blind and partially blind patients, the researchers say, and could obviate the need for costly eye surgeries and other treatments.

Previous studies have shown that SSDs help congenitally blind people navigate their environments. This most recent study, led by Michael Proulx from the University of Bath and published in Frontiers In Cognitive Science, instead tested how quickly and effectively blindfolded, sighted people could use one such device, the vOICe. The point? People who've been blind most of their lives typically compensate for their lack of vision with sharpened hearing and other senses. Not so with the newly blind. The researchers wanted to prove that their device could work on those who've just lost their sight, too.

The vOICe consists of a backpack carrying a laptop, some sunglasses equipped with a camera, and earbuds. Here's how it works, according to the study:

The vOICe converts images captured by a camera into "soundscapes" delivered to the user through headphones at a default rate of one soundscape per second. Each soundscape is a left to right scan of the visual scene with frequency representing the image's vertical axis and loudness representing brightness... The user therefore experiences a series of "snapshots" passing from the left to the right ear.

A simple example would be a black screen with four slanted white lines, a bit like this (but with inverted colors):

/ / / / The "soundscape" for that image would be four distinct, loud bleeps, each with an escalating pitch. Actually navigating the big outside world would be challenging, but--with enough practice and skill--perhaps doable. One user described it as "Like figuring out where you're walking in the dark," the study notes. For those who learn best through experience, this video does a good job of simulating it (warning: harsh, loud noises):

Vision is measured in terms of acuity: 20/20 vision means that you can see from 20 feet what a normal person can see (often in terms of the eye chart); 20/40 means you can see from 20 feet what a normal person would be able to see from 40 feet. In the U.S., legal blindness is 20/200 (or worse).

In Proulx's study, blindfolded subjects equipped with the vOICe (or just headphones playing the associated sound profile, depending on the experiment) were asked to report on the orientation of E’s from a Snellen eye chart on a computer screen in front of them. The size of the E's corresponds to the acuity rating, as this chart displays. The vOICe allowed most subjects to report with 75 percent accuracy at an acuity of 20/2464-20/4682, with an absolute upper-bound of 20/408 (which means the letters had to be pretty big for them to accurately say which direction they faced). Keeping in mind both that this isn't actual vision and that these are inexperienced users, the results are promising, the researchers say. Of course, there's a big difference between using the device in a controlled lab setting and actually taking it out on a noisy, crowded city street. And I bet the constant, screechy noise would take some adjusting to. Nevertheless, I’m sure this guy is intrigued.

Tuesday, August 13, 2013

Gene Breakthroughs Spark a Revolution in Cancer Treatment

Gene Breakthroughs Spark a Revolution in Cancer Treatment

    By Ron Winslow
    Kellie Carey's doctor finally stopped dodging questions about how long she had to live six weeks after he diagnosed her lung cancer.

"Maybe three months," he told her in his office one sunny May morning in 2010, she recalls.

Yet she is still alive, a testament to the most extraordinary decade of progress ever in the long scientific struggle against lung cancer.

Tests found Ms. Carey's lung cancer to be of a rare type that researchers had found just three years earlier by deciphering its genetic code. The 45-year-old businesswoman in 2010 went on a drug Pfizer Inc. PFE +0.27% was testing for that type. By pinpointing her cancer, the drug probably helped give her years more to live than chemotherapy would have, her doctors say

That is remarkable because lung cancer for decades defied efforts to find drugs that could extend an average patient's life by even a few weeks.

But an explosion in knowledge about the genetic mutations that cause tumors is just now offering the first real promise of drugs that can control what is the most-common and most-deadly cancer.

Ms. Carey has one of at least 15 lung-cancer variations, almost all of which scientists didn't know existed 10 years ago. Researchers have identified those variations, most of them in just the past four years, by decoding DNA in tumors—akin to how crime labs analyze DNA to genetically fingerprint suspects.The drugs don't cure cancer and face significant hurdles. But doctors now talk of a "precision medicine" approach in which those pinpoint drugs can treat tumors far more effectively than catchall chemotherapy.The newfound variants have led major cancer centers to revamp their approach to treating cancer and have spurred a rush among drug companies to find medicines that narrowly target each one.

"What we're seeing is the beginning of a revolution in therapeutics," says Janet Woodcock, director of the Food and Drug Administration's Center for Drug Evaluation and Research. "We can only hope that this gets us to where cancer is managed or curable."

Among signs that revolution really is afoot: A June 2013 study found that lung-cancer patients who were treated with drugs targeted at their genetically identified varieties lived 1.4 years longer than patients on chemotherapy whose cancers weren't genetically identified.

In effect, lung cancer is no longer a few common diagnoses. Instead, it is a growing list of rare cancers, each a target for its own drug regimen.

"It's likely that more than half of tumors have some alteration we can target with a drug," says John V. Heymach, a lung-cancer specialist at MD Anderson Cancer Center, Houston. "They may not all have the same success, but we know that in many cases, a targeted agent will work very well."

The same goes for other malignancies: Scientists have decoded tumor DNA from breast, colon, kidney, skin and other cancers in recent years to discover scores of variations they didn't know existed before.

Research hospitals like MD Anderson, Vanderbilt University and Massachusetts General Hospital are among a growing number of cancer practices that routinely decode the tumor DNA of most patients with advanced cancer.

The lists of newfound variations have invigorated the drug industry, with companies like Pfizer, Roche Holding AG ROG.VX +0.38% and Merck MRK -0.08% & Co. racing to develop drugs that target each one.

Last year, nearly 1,000 cancer drugs were in clinical development, up 52% from 2006, says the Pharmaceutical Research and Manufacturers of America, a trade group. The "vast majority" of that growth is from drugs targeted at genetic mutations, says Bill Chin, the group's head of science and regulatory affairs.

Three drugs are on the market for newly discovered lung-cancer mutations. Dozens more are in clinical trials. Some approved for other cancers appear effective for specific lung cancers. And drug companies are targeting other mutations of all cancer types.

At least half the 27 medicines on Novartis AG's NOVN.VX +0.74% current list of oncology drugs in clinical development target cancer mutations. Precision medicine is "fundamentally changing the way we think about cancer drug development," says Hervé Hoppenot, president of the company's Novartis Oncology unit.

Just last year, the FDA established a "breakthrough therapy designation" to hasten approval of experimental drugs that show striking benefits in early trials, including those targeted at cancer mutations.

Ms. Carey's diagnosis in 2010 came just as that thinking was starting to change. Her roller-coaster ride of cancer remission and recurrence over the next three years shows the promise and shortcomings of precision medicine.

Ms. Carey, who worked for a business selling private jets, suffered an apparent seizure at her gym. Doctors discovered a nodule in her lung of cancer that had spread to her brain. Surgery and radiation treated the brain tumor.

But when the New York City resident's doctor said she probably had three months left, "I definitely felt like there were no options," she says.

It wasn't an unusual prognosis for lung cancer in 2010. Three decades of research starting in the 1970s into hundreds of potential lung-cancer drugs had produced dismal results, says MD Anderson's Dr. Heymach: Over that time, a lung-cancer patient's median survival improved by just one month, to eight months.

Ms. Carey found hope in news accounts of a drug Pfizer was testing against a cancer type researchers had identified in 2007. The type was caused by a mutation in the so-called ALK gene—it normally plays a role in brain development—and Ms. Carey wanted to know if that was her cancer.

In 2010, precision medicine was still so nascent that Ms. Carey had to show unusual persistence. Few doctors even considered testing tumors for mutations.

She says she had to demand the test. "Are you helping to save my life," she recalls asking her doctor at the time, "or just waiting for me to die?"

That ALK-gene mutation was only the second mutation researchers had identified using advanced DNA-sequencing technology on lung-cancer tumors. The first was in 2004, a mutation in the so-called EGFR gene that responded well to an existing drug, Tarceva, now sold by Roche. (Another mutation, KRAS was discovered previously, with earlier technology.)

The discovery of the role of the EGFR mutation in 2004 sparked the search for more cancer-causing mutations.

Before that, a pathologist would identify a patient's lung-cancer tumors through a microscope to see if they were of the "small-cell" or "non-small-cell" variety. The difference helped determine which regimen of chemotherapy to prescribe.

After finding the ALK-gene mutation, researchers in 2007 found another mutation. By 2010, for a few lucky patients whose tumors proved to be of the newly discovered varieties, there were a few drugs on the market or in trials.

Ms. Carey was among the fortunate: Her mutation proved to be of the ALK gene, which represents about 5% of lung-cancer cases.

The discovery of the ALK-gene mutation had prompted Pfizer to test a drug already in its portfolio, brand-named Xalkori and generically called crizotinib, to see if it worked on the mutation. Pfizer's study of the first patients showed dramatic results, which Ms. Carey read about.

Again, Ms. Carey needed persistence, this time to get the drug. She visited different sites participating in Pfizer's trials before finding a slot at the University of Chicago.

Within six weeks, two of three cancerous nodules in her lungs had disappeared, and the third had shrunk significantly.

The FDA approved the Pfizer drug in 2011 based on 250 patients, four years after the ALK-mutation link was discovered. That is lightning speed in an industry accustomed to spending a decade with thousands of test subjects to get drug approval.

Ms. Carey in 2011 began buying the Pfizer drug by prescription. It was expensive—today Pfizer charges $10,800 a month for it—but her insurance covered it.

Prices like that raise questions about the affordability of precision medicine. But those prices, and the speed at which genetically targeted drugs can come to market, had begun changing the economics of drug development.

The "precision medicine approach requires people to change the way they look at opportunities," says Mace Rothenberg, a senior vice president who heads cancer clinical development for Pfizer. Instead of trying to apply a drug to the largest number of patients possible, it is possible to "demonstrate very significant value of the drug to the patient, the physician, the payers and the company."

Discovery of new mutations accelerated. A 2011 report linked a mutation of a gene called RET to lung cancer, prompting researchers at Memorial Sloan-Kettering Cancer in New York to approach Exelixis Inc. EXEL -0.61% The South San Francisco biotechnology company was developing a drug called cabozantinib to treat a rare form of thyroid cancer linked to the RET mutation.

That mutation is found in only about 1% of lung-cancer patients, but Sloan-Kettering launched a drug trial. The first few patients tested had striking benefits. "These were patients who had nothing six months earlier," says Mark Kris, a lung-cancer specialist at Sloan-Kettering.

Discovery of still-more lung cancer mutations continued in rapid fire. The count is 15 today, accounting for about 60% of all lung cancers, according to some estimates, and researchers expect to find more.

Precision medicine is no cure. A tumor with a pinpointed mutation doesn't always respond to a drug targeted at it. The drug often shrinks tumors within weeks. But the tumors can develop resistance and come roaring back.

Ms. Carey's cancer found a way around the treatment, in early 2012. An analysis of her tumor found the ALK-gene mutation still active. She took to calling her mutation the "Darth Vader of cells."

Doctors think most patients will need a series of precision drugs, sometimes with chemotherapy. "The tumor will keep evading our best therapies," says Trever Bivona, a lung-cancer researcher at University of California San Francisco. "Ultimately we're going to have to get to combination approaches." exdiscovery of new

Ms. Carey in the spring of 2012 went off crizotinib for another regimen of brain radiation, then went back on the drug.

By that year, interest was surging among drug companies in targeted drugs. At least three "next-generation crizotinibs" against the ALK-gene mutation were now in trials. Ms. Carey entered a trial for one of them, being developed by Ariad Pharmaceuticals Inc. ARIA +0.27%

Not all patients can find a trial. Precision drugs are approved for only two lung-cancer mutations, the ALK and the EGFR-gene mutations. A patient with a different mutation must look for a drug in development and try to join its trial.

Dr. Bivona of University of California San Francisco says he treated a patient this year who died a month before the launch of a clinical trial for a drug that matched the patient's mutation. "We were in a black hole," he says. "Getting drugs to the patients who need them will take an entire remodeling of the drug-development system."

While there are drugs approved for other cancers that appear effective for some newfound lung cancers, insurers generally feel data don't yet justify coverage of such "off-label" drugs. And for several of the 15 known lung-cancer variants, an especially promising drug has yet to emerge.

Tests for mutations are less likely to be available in smaller doctors' offices. Even many large centers are just putting in place systems to act on the information. "A lot of places can tell you they do this now, but few really have the people in place who know what to do," says Roy Herbst, chief of medical oncology at Yale Cancer Center, New Haven, Conn., who is Ms. Carey's current oncologist.

But rapid diagnostic advances are making it easier for any doctor to test for the newfound cancers. Tests now can hunt for more than 200 mutations—of lung and other cancers—in one biopsy.

Evidence that precision medicine works will likely broaden its use quickly. A June 2013 report on 1,007 patients with advanced lung cancer whose tumors were sequenced by a group of researchers called the Lung Cancer Mutation Consortium found that 62% had alterations suspected of being driver mutations.

The researchers reported that the 265 patients on the study treated with a targeted drug had a median survival of 3.5 years from diagnosis, compared with 2.1 years for the 361 patients for whom a mutation wasn't identified.

"It opens up so many more doors for patients if you can find their target," says Alice Shaw, an oncologist at Mass General in Boston.

At Ms. Carey's checkup late this July, her doctor said her new drug regimen is keeping her lung tumor from progressing.

She is also considering a new class of drugs called PD-1 inhibitors that enlist the immune system. Such agents from Merck, Roche and Bristol-Myers Squibb Co.BMY +0.51% are creating a buzz among oncologists for use in parallel with the genomic strategy.

"Now when I look back, I'm astonished at the timing of everything," she says.

"My quality of life is extraordinary," she says. "The science in this and the positive response I've had—I wouldn't be alive without that."

Write to Ron Winslow at

A version of this article appeared August 12, 2013, on page A1 in the U.S. edition of The Wall Street Journal, with the headline: Gene Breakthroughs Spark A Revolution in Cancer Treatment.