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#434648 The Pediatric AI That Outperformed ...
Training a doctor takes years of grueling work in universities and hospitals. Building a doctor may be as easy as teaching an AI how to read.
Artificial intelligence has taken another step towards becoming an integral part of 21st-century medicine. New research out of Guangzhou, China, published February 11th in Nature Medicine Letters, has demonstrated a natural-language processing AI that is capable of out-performing rookie pediatricians in diagnosing common childhood ailments.
The massive study examined the electronic health records (EHR) from nearly 600,000 patients over an 18-month period at the Guangzhou Women and Children’s Medical Center and then compared AI-generated diagnoses against new assessments from physicians with a range of experience.
The verdict? On average, the AI was noticeably more accurate than junior physicians and nearly as reliable as the more senior ones. These results are the latest demonstration that artificial intelligence is on the cusp of becoming a healthcare staple on a global scale.
Less Like a Computer, More Like a Person
To outshine human doctors, the AI first had to become more human. Like IBM’s Watson, the pediatric AI leverages natural language processing, in essence “reading” written notes from EHRs not unlike how a human doctor would review those same records. But the similarities to human doctors don’t end there. The AI is a machine learning classifier (MLC), capable of placing the information learned from the EHRs into categories to improve performance.
Like traditionally-trained pediatricians, the AI broke cases down into major organ groups and infection areas (upper/lower respiratory, gastrointestinal, etc.) before breaking them down even further into subcategories. It could then develop associations between various symptoms and organ groups and use those associations to improve its diagnoses. This hierarchical approach mimics the deductive reasoning human doctors employ.
Another key strength of the AI developed for this study was the enormous size of the dataset collected to teach it: 1,362,559 outpatient visits from 567,498 patients yielded some 101.6 million data points for the MLC to devour on its quest for pediatric dominance. This allowed the AI the depth of learning needed to distinguish and accurately select from the 55 different diagnosis codes across the various organ groups and subcategories.
When comparing against the human doctors, the study used 11,926 records from an unrelated group of children, giving both the MLC and the 20 humans it was compared against an even playing field. The results were clear: while cohorts of senior pediatricians performed better than the AI, junior pediatricians (those with 3-15 years of experience) were outclassed.
Helping, Not Replacing
While the research used a competitive analysis to measure the success of the AI, the results should be seen as anything but hostile to human doctors. The near future of artificial intelligence in medicine will see these machine learning programs augment, not replace, human physicians. The authors of the study specifically call out augmentation as the key short-term application of their work. Triaging incoming patients via intake forms, performing massive metastudies using EHRs, providing rapid ‘second opinions’—the applications for an AI doctor that is better-but-not-the-best are as varied as the healthcare industry itself.
That’s only considering how artificial intelligence could make a positive impact immediately upon implementation. It’s easy to see how long-term use of a diagnostic assistant could reshape the way modern medical institutions approach their work.
Look at how the MLC results fit snugly between the junior and senior physician groups. Essentially, it took nearly 15 years before a physician could consistently out-diagnose the machine. That’s a decade and a half wherein an AI diagnostic assistant would be an invaluable partner—both as a training tool and a safety measure. Likewise, on the other side of the experience curve you have physicians whose performance could be continuously leveraged to improve the AI’s effectiveness. This is a clear opportunity for a symbiotic relationship, with humans and machines each assisting the other as they mature.
Closer to Us, But Still Dependent on Us
No matter the ultimate application, the AI doctors of the future are drawing nearer to us step by step. This latest research is a demonstration that artificial intelligence can mimic the results of human deductive reasoning even in some of the most complex and important decision-making processes. True, the MLC required input from humans to function; both the initial data points and the cases used to evaluate the AI depended on EHRs written by physicians. While every effort was made to design a test schema that removed any indication of the eventual diagnosis, some “data leakage” is bound to occur.
In other words, when AIs use human-created data, they inherit human insight to some degree. Yet the progress made in machine imaging, chatbots, sensors, and other fields all suggest that this dependence on human input is more about where we are right now than where we could be in the near future.
Data, and More Data
That near future may also have some clear winners and losers. For now, those winners seem to be the institutions that can capture and apply the largest sets of data. With a rapidly digitized society gathering incredible amounts of data, China has a clear advantage. Combined with their relatively relaxed approach to privacy, they are likely to continue as one of the driving forces behind machine learning and its applications. So too will Google/Alphabet with their massive medical studies. Data is the uranium in this AI arms race, and everyone seems to be scrambling to collect more.
In a global community that seems increasingly aware of the potential problems arising from this need for and reliance on data, it’s nice to know there’ll be an upside as well. The technology behind AI medical assistants is looking more and more mature—even if we are still struggling to find exactly where, when, and how that technology should first become universal.
Yet wherever we see the next push to make AI a standard tool in a real-world medical setting, I have little doubt it will greatly improve the lives of human patients. Today Doctor AI is performing as well as a human colleague with more than 10 years of experience. By next year or so, it may take twice as long for humans to be competitive. And in a decade, the combined medical knowledge of all human history may be a tool as common as a stethoscope in your doctor’s hands.
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Posted in Human Robots
#434580 How Genome Sequencing and Senolytics Can ...
The causes of aging are extremely complex and unclear. With the dramatic demonetization of genome reading and editing over the past decade, and Big Pharma, startups, and the FDA starting to face aging as a disease, we are starting to find practical ways to extend our healthspan.
Here, in Part 2 of a series of blogs on longevity and vitality, I explore how genome sequencing and editing, along with new classes of anti-aging drugs, are augmenting our biology to further extend our healthy lives.
In this blog I’ll cover two classes of emerging technologies:
Genome Sequencing and Editing;
Senolytics, Nutraceuticals & Pharmaceuticals.
Let’s dive in.
Genome Sequencing & Editing
Your genome is the software that runs your body.
A sequence of 3.2 billion letters makes you “you.” These base pairs of A’s, T’s, C’s, and G’s determine your hair color, your height, your personality, your propensity to disease, your lifespan, and so on.
Until recently, it’s been very difficult to rapidly and cheaply “read” these letters—and even more difficult to understand what they mean.
Since 2001, the cost to sequence a whole human genome has plummeted exponentially, outpacing Moore’s Law threefold. From an initial cost of $3.7 billion, it dropped to $10 million in 2006, and to $5,000 in 2012.
Today, the cost of genome sequencing has dropped below $500, and according to Illumina, the world’s leading sequencing company, the process will soon cost about $100 and take about an hour to complete.
This represents one of the most powerful and transformative technology revolutions in healthcare.
When we understand your genome, we’ll be able to understand how to optimize “you.”
We’ll know the perfect foods, the perfect drugs, the perfect exercise regimen, and the perfect supplements, just for you.
We’ll understand what microbiome types, or gut flora, are ideal for you (more on this in a later blog).
We’ll accurately predict how specific sedatives and medicines will impact you.
We’ll learn which diseases and illnesses you’re most likely to develop and, more importantly, how to best prevent them from developing in the first place (rather than trying to cure them after the fact).
CRISPR Gene Editing
In addition to reading the human genome, scientists can now edit a genome using a naturally-occurring biological system discovered in 1987 called CRISPR/Cas9.
Short for Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein 9, the editing system was adapted from a naturally-occurring defense system found in bacteria.
Here’s how it works:
The bacteria capture snippets of DNA from invading viruses (or bacteriophage) and use them to create DNA segments known as CRISPR arrays.
The CRISPR arrays allow the bacteria to “remember” the viruses (or closely related ones), and defend against future invasions.
If the viruses attack again, the bacteria produce RNA segments from the CRISPR arrays to target the viruses’ DNA. The bacteria then use Cas9 to cut the DNA apart, which disables the virus.
Most importantly, CRISPR is cheap, quick, easy to use, and more accurate than all previous gene editing methods. As a result, CRISPR/Cas9 has swept through labs around the world as the way to edit a genome.
A short search in the literature will show an exponential rise in the number of CRISPR-related publications and patents.
2018: Filled With CRISPR Breakthroughs
Early results are impressive. Researchers from the University of Chicago recently used CRISPR to genetically engineer cocaine resistance into mice.
Researchers at the University of Texas Southwestern Medical Center used CRISPR to reverse the gene defect causing Duchenne muscular dystrophy (DMD) in dogs (DMD is the most common fatal genetic disease in children).
With great power comes great responsibility, and moral and ethical dilemmas.
In 2015, Chinese scientists sparked global controversy when they first edited human embryo cells in the lab with the goal of modifying genes that would make the child resistant to smallpox, HIV, and cholera.
Three years later, in November 2018, researcher He Jiankui informed the world that the first set of CRISPR-engineered female twins had been delivered.
To accomplish his goal, Jiankui deleted a region of a receptor on the surface of white blood cells known as CCR5, introducing a rare, natural genetic variation that makes it more difficult for HIV to infect its favorite target, white blood cells.
Setting aside the significant ethical conversations, CRISPR will soon provide us the tools to eliminate diseases, create hardier offspring, produce new environmentally resistant crops, and even wipe out pathogens.
Senolytics, Nutraceuticals & Pharmaceuticals
Over the arc of your life, the cells in your body divide until they reach what is known as the Hayflick limit, or the number of times a normal human cell population will divide before cell division stops, which is typically about 50 divisions.
What normally follows next is programmed cell death or destruction by the immune system. A very small fraction of cells, however, become senescent cells and evade this fate to linger indefinitely.
These lingering cells secrete a potent mix of molecules that triggers chronic inflammation, damages the surrounding tissue structures, and changes the behavior of nearby cells for the worse.
Senescent cells appear to be one of the root causes of aging, causing everything from fibrosis and blood vessel calcification, to localized inflammatory conditions such as osteoarthritis, to diminished lung function.
Fortunately, both the scientific and entrepreneurial communities have begun to work on senolytic therapies, moving the technology for selectively destroying senescent cells out of the laboratory and into a half-dozen startup companies.
Prominent companies in the field include the following:
Unity Biotechnology is developing senolytic medicines to selectively eliminate senescent cells with an initial focus on delivering localized therapy in osteoarthritis, ophthalmology and pulmonary disease.
Oisin Biotechnologiesis pioneering a programmable gene therapy that can destroy cells based on their internal biochemistry.
SIWA Therapeuticsis working on an immunotherapy approach to the problem of senescent cells.
In recent years, researchers have identified or designed a handful of senolytic compounds that can curb aging by regulating senescent cells. Two of these drugs that have gained mainstay research traction are rapamycin and metformin.
Rapamycin
Originally extracted from bacteria found on Easter Island, Rapamycin acts on the m-TOR (mechanistic target of rapamycin) pathway to selectively block a key protein that facilitates cell division.
Currently, rapamycin derivatives are widely used as immunosuppression in organ and bone marrow transplants. Research now suggests that use results in prolonged lifespan and enhanced cognitive and immune function.
PureTech Health subsidiary resTORbio (which started 2018 by going public) is working on a rapamycin-based drug intended to enhance immunity and reduce infection. Their clinical-stage RTB101 drug works by inhibiting part of the mTOR pathway.
Results of the drug’s recent clinical trial include:
Decreased incidence of infection
Improved influenza vaccination response
A 30.6 percent decrease in respiratory tract infections
Impressive, to say the least.
Metformin
Metformin is a widely-used generic drug for mitigating liver sugar production in Type 2 diabetes patients.
Researchers have found that Metformin also reduces oxidative stress and inflammation, which otherwise increase as we age.
There is strong evidence that Metformin can augment cellular regeneration and dramatically mitigate cellular senescence by reducing both oxidative stress and inflammation.
Over 100 studies registered on ClinicalTrials.gov are currently following up on strong evidence of Metformin’s protective effect against cancer.
Nutraceuticals and NAD+
Beyond cellular senescence, certain critical nutrients and proteins tend to decline as a function of age. Nutraceuticals combat aging by supplementing and replenishing these declining nutrient levels.
NAD+ exists in every cell, participating in every process from DNA repair to creating the energy vital for cellular processes. It’s been shown that NAD+ levels decline as we age.
The Elysium Health Basis supplement aims to elevate NAD+ levels in the body to extend one’s lifespan. Elysium’s clinical study reports that Basis increases NAD+ levels consistently by a sustained 40 percent.
Conclusion
These are just a taste of the tremendous momentum that longevity and aging technology has right now. As artificial intelligence and quantum computing transform how we decode our DNA and how we discover drugs, genetics and pharmaceuticals will become truly personalized.
The next blog in this series will demonstrate how artificial intelligence is converging with genetics and pharmaceuticals to transform how we approach longevity, aging, and vitality.
We are edging closer to a dramatically extended healthspan—where 100 is the new 60. What will you create, where will you explore, and how will you spend your time if you are able to add an additional 40 healthy years to your life?
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Posted in Human Robots
#433939 The Promise—and Complications—of ...
Every year, for just a few days in a major city, a small team of roboticists get to live the dream: ordering around their own personal robot butlers. In carefully-constructed replicas of a restaurant scene or a domestic setting, these robots perform any number of simple algorithmic tasks. “Get the can of beans from the shelf. Greet the visitors to the museum. Help the humans with their shopping. Serve the customers at the restaurant.”
This is Robocup @ Home, the annual tournament where teams of roboticists put their autonomous service robots to the test for practical domestic applications. The tasks seem simple and mundane, but considering the technology required reveals that they’re really not.
The Robot Butler Contest
Say you want a robot to fetch items in the supermarket. In a crowded, noisy environment, the robot must understand your commands, ask for clarification, and map out and navigate an unfamiliar environment, avoiding obstacles and people as it does so. Then it must recognize the product you requested, perhaps in a cluttered environment, perhaps in an unfamiliar orientation. It has to grasp that product appropriately—recall that there are entire multi-million-dollar competitions just dedicated to developing robots that can grasp a range of objects—and then return it to you.
It’s a job so simple that a child could do it—and so complex that teams of smart roboticists can spend weeks programming and engineering, and still end up struggling to complete simplified versions of this task. Of course, the child has the advantage of millions of years of evolutionary research and development, while the first robots that could even begin these tasks were only developed in the 1970s.
Even bearing this in mind, Robocup @ Home can feel like a place where futurist expectations come crashing into technologist reality. You dream of a smooth-voiced, sardonic JARVIS who’s already made your favorite dinner when you come home late from work; you end up shouting “remember the biscuits” at a baffled, ungainly droid in aisle five.
Caring for the Elderly
Famously, Japan is one of the most robo-enthusiastic nations in the world; they are the nation that stunned us all with ASIMO in 2000, and several studies have been conducted into the phenomenon. It’s no surprise, then, that humanoid robotics should be seriously considered as a solution to the crisis of the aging population. The Japanese government, as part of its robots strategy, has already invested $44 million in their development.
Toyota’s Human Support Robot (HSR-2) is a simple but programmable robot with a single arm; it can be remote-controlled to pick up objects and can monitor patients. HSR-2 has become the default robot for use in Robocup @ Home tournaments, at least in tasks that involve manipulating objects.
Alongside this, Toyota is working on exoskeletons to assist people in walking after strokes. It may surprise you to learn that nurses suffer back injuries more than any other occupation, at roughly three times the rate of construction workers, due to the day-to-day work of lifting patients. Toyota has a Care Assist robot/exoskeleton designed to fix precisely this problem by helping care workers with the heavy lifting.
The Home of the Future
The enthusiasm for domestic robotics is easy to understand and, in fact, many startups already sell robots marketed as domestic helpers in some form or another. In general, though, they skirt the immensely complicated task of building a fully capable humanoid robot—a task that even Google’s skunk-works department gave up on, at least until recently.
It’s plain to see why: far more research and development is needed before these domestic robots could be used reliably and at a reasonable price. Consumers with expectations inflated by years of science fiction saturation might find themselves frustrated as the robots fail to perform basic tasks.
Instead, domestic robotics efforts fall into one of two categories. There are robots specialized to perform a domestic task, like iRobot’s Roomba, which stuck to vacuuming and became the most successful domestic robot of all time by far.
The tasks need not necessarily be simple, either: the impressive but expensive automated kitchen uses the world’s most dexterous hands to cook meals, providing it can recognize the ingredients. Other robots focus on human-robot interaction, like Jibo: they essentially package the abilities of a voice assistant like Siri, Cortana, or Alexa to respond to simple questions and perform online tasks in a friendly, dynamic robot exterior.
In this way, the future of domestic automation starts to look a lot more like smart homes than a robot or domestic servant. General robotics is difficult in the same way that general artificial intelligence is difficult; competing with humans, the great all-rounders, is a challenge. Getting superhuman performance at a more specific task, however, is feasible and won’t cost the earth.
Individual startups without the financial might of a Google or an Amazon can develop specialized robots, like Seven Dreamers’ laundry robot, and hope that one day it will form part of a network of autonomous robots that each have a role to play in the household.
Domestic Bliss?
The Smart Home has been a staple of futurist expectations for a long time, to the extent that movies featuring smart homes out of control are already a cliché. But critics of the smart home idea—and of the internet of things more generally—tend to focus on the idea that, more often than not, software just adds an additional layer of things that can break (NSFW), in exchange for minimal added convenience. A toaster that can short-circuit is bad enough, but a toaster that can refuse to serve you toast because its firmware is updating is something else entirely.
That’s before you even get into the security vulnerabilities, which are all the more important when devices are installed in your home and capable of interacting with them. The idea of a smart watch that lets you keep an eye on your children might sound like something a security-conscious parent would like: a smart watch that can be hacked to track children, listen in on their surroundings, and even fool them into thinking a call is coming from their parents is the stuff of nightmares.
Key to many of these problems is the lack of standardization for security protocols, and even the products themselves. The idea of dozens of startups each developing a highly-specialized piece of robotics to perform a single domestic task sounds great in theory, until you realize the potential hazards and pitfalls of getting dozens of incompatible devices to work together on the same system.
It seems inevitable that there are yet more layers of domestic drudgery that can be automated away, decades after the first generation of time-saving domestic devices like the dishwasher and vacuum cleaner became mainstream. With projected market values into the billions and trillions of dollars, there is no shortage of industry interest in ironing out these kinks. But, for now at least, the answer to the question: “Where’s my robot butler?” is that it is gradually, painstakingly learning how to sort through groceries.
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Posted in Human Robots