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  • richardmitnick 12:55 pm on September 12, 2019 Permalink | Reply
    Tags: "Poor Motor Skills Predict Long-Term Language Impairments For Children with Autism, , , Medicine, Rutgers Study Finds",   

    From Rutgers University: “Poor Motor Skills Predict Long-Term Language Impairments For Children with Autism, Rutgers Study Finds” 

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    From Rutgers University

    September 10, 2019
    Megan Schumann
    MEGAN.SCHUMANN@rutgers.edu
    848-445-1907

    1
    Fine motor skills may be a strong predictor for identifying whether children with autism are at risk for long-term language disabilities, according to a Rutgers-led study. Shutterstock

    Fine motor skills – used for eating, writing and buttoning clothing – may be a strong predictor for identifying whether children with autism are at risk for long-term language disabilities, according to a Rutgers-led study.

    The study, in the Journal of Child Psychology and Psychiatry, highlights the association between fine motor skills and their later language development in young speech-delayed children with autism who, at approximately age three, are nonverbal or using primarily single words to communicate.

    In an American sample of language-delayed children with autism, researchers found that nearly half had extremely delayed fine motor skills. Of this group, 77.5 percent who had extremely delayed motor skills continued to have language disabilities in later childhood or young adulthood. By contrast, 69.6 percent of children who demonstrated less impaired fine motor skills overcame their language delays by late childhood or young adulthood.

    In a second study of Canadian children with autism, researchers found that those with extremely delayed fine motor skills made fewer gains in expressive language.

    “Language development is complex. Many interventions for young children with autism focus on language intervention or social skills,” said lead researcher Vanessa Bal, the Karmazin and Lillard Chair in Adult Autism at Rutgers University-New Brunswick’s Graduate School of Applied and Professional Psychology. “But our findings indicate it may be useful for clinicians and parents to assess fine motor skills and build opportunities for these skills to be further developed, in order to help with language development.”

    The researchers analyzed data from existing studies that used different standardized developmental tests to assess fine motor skills through tasks that require children to manipulate small objects, such as picking up Cheerios or stacking small blocks.

    The first analyses focused on 86 children with autism recruited to an American study from before their second birthday to age 19. The replication study was conducted using data from a Canadian study that followed 181 children with autism from two to four years of age, until age 10.

    The Rutgers-led researchers analyzed the American study and found the link between fine motor skills and later language ability. They replicated the findings in the Canadian study sample. Replication in independent samples, using different developmental tests of fine motor skills is a strength of this study and underscores the potential importance of the findings.

    The study was a collaboration between Dr. Bal’s Rutgers LifeSPAN ASD Lab, and researchers from University of California Los Angeles, and the Canadian Pathways Study.

    See the full article here .


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  • richardmitnick 10:06 am on September 9, 2019 Permalink | Reply
    Tags: "When You Don’t Know You Feel Alone in the World", , Medicine, , Undiagnosed Diseases Network   

    From Stanford University: “When You Don’t Know, You Feel Alone in the World” 

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    From Stanford University

    The odyssey of the undiagnosed.

    9.9.19

    By Deni Ellis Béchard
    Photography by Timothy Archibald

    1
    IT’S GENETIC: Carson’s cerebral palsy diagnosis had to be thrown out after his brother, Chase, began to show similar symptoms.

    Danny Miller was spending every free minute searching the internet, reading page after page about medical conditions. His son, Carson, was a year old, and Miller believed something was wrong with him. He and his wife, Nikki, had noticed the first signs a few months earlier, during playdates with other children. He couldn’t exactly put his finger on the problem. “It was just the quality of movement and the types of movement,” Miller recalls. “He didn’t like tummy time. The movements were a little bit stiff and not as smooth as the other kids’.”

    During an appointment with the pediatrician, the Millers were told that children develop at different rates. And yet Carson’s hands were curled tightly into fists, and his movements showed signs of spasticity. The Millers set up appointments with neurologists and behavior specialists, all of whom said there was probably nothing to worry about.

    “That’s when I sort of began to dive into my research career,” Miller says. “I was looking at different conditions and would just enter symptoms into Google to figure out what would come up or what would explain why he wasn’t crawling, why he wasn’t pulling himself up to standing.”

    The condition that Miller repeatedly circled back to was cerebral palsy. Its symptoms matched Carson’s: tremors, muscle weakness and lack of coordination. The cause was often unknown and usually attributed to atypical brain development or damage during pregnancy or childbirth, or shortly afterward. Miller continued taking Carson to see specialists, and Carson finally received a diagnosis of cerebral palsy in 2013, when he was 15 months old.

    Shortly afterward, the Millers had their second son, Chase. The pregnancy was easy, and the baby looked healthy. “But fast forward to 6, 7 months of age,” Miller says, “[and] we began to see some of the same things. That’s when we really began to get worried.”

    Suddenly, the cerebral palsy diagnosis seemed unlikely. CP occurs in approximately 2 out of 1,000 births and in 1 out of 1,000 that are not premature. The odds of both boys having it were 1 in a million. Miller turned his research toward genetic movement disorders. Testing for the boys was now more extensive: metabolomics (the study of the body’s metabolic byproducts, such as lactic acid or nitrogen compounds), karyotyping (the evaluation of the chromosomes for structural abnormalities), gene panels (to test for common mutations) and then sequencing of the entire exome (the genome’s coding portions, which are expressed in proteins and linked to traits). The brothers also received several MRIs. Carson’s showed lesions in the brain’s basal ganglia, an area important for motor activity. But the neurologist couldn’t identify the cause. Many disorders—among them many rare diseases—could cause lesions.

    As the Millers did test after test for their sons, the boys’ physical development plateaued. By the time Carson was 5 and Chase was 3, neither could speak or walk, and their motor control was extremely limited, and yet both boys appeared to be cognitively intact and could understand spoken language. Though Miller continued researching diseases online, none of the symptoms quite fit.

    In 2016, Miller read about the Undiagnosed Diseases Network, a research initiative created by the National Institutes of Health in 2014 in conjunction with six clinical sites at academic medical centers, including Stanford. The UDN accepted its first patients—adults as well as children—in September 2015. In its first 20 months, it would evaluate 601 patients, find diagnoses for 35 percent of them and identify 31 previously unknown syndromes. In 2019, it expanded to include a dozen clinical sites, and it has now accepted 1,393 patients, evaluated 1,190 of them and made 330 diagnoses. The network works collaboratively, sharing data and resources and bringing together the best specialists from multiple institutions to take on the most challenging medical cases. It refuses no one on the basis of ability to pay. The only standard is whether the person has, according to the website, a condition that includes at least one objective medical finding—a detectable biological anomaly—and “that remains undiagnosed despite thorough evaluation.”

    For the Millers, the UDN was a lifeline after a long, repetitive and frustrating search.

    “It was sort of the end of the line for undiagnosed families,” Miller recalls. He spent the next several months compiling his sons’ medical records. In the spring of 2016, he applied on their behalf to the UDN. By December, they were admitted, and since they lived in Corte Madera, Calif., a 30-minute drive north of San Francisco, they were assigned to Stanford’s Center for Undiagnosed Diseases.

    “It was very scary,” Miller says, recalling the stress of four years of searching for answers and coming up empty. “As a parent, you go through a lot of self-doubt, a lot of blame. You wonder, ‘What did we do wrong? Did I not take care of my body the right way as a young man and now that’s had an impact on our children?’ My wife went through a period where she asked, what did she do wrong during her pregnancy? Did she not get proper nutrition? We were both really determined to try to find answers, and we weren’t getting them.”

    The Millers’ first visit to Stanford was in early 2017. Again, they went through a series of consultations with specialists. The team then decided to do whole-genome sequencing for the family—the parents as well
    as Carson and Chase.

    A little more than a year later, the Millers had an answer.

    The head of pediatrics at Stanford’s Center for Undiagnosed Diseases is associate professor Jon Bernstein, MD ’03, PhD ’03, a pediatric medical geneticist who chose his field of study because it combined the kind of challenging problem solving he found satisfying with a lifelong love of working with children.

    After he joined Stanford Medicine’s faculty in 2008, much of his focus was on helping families find explanations for their children’s chronic conditions. When he heard that several colleagues were applying to join the UDN, he wrote to say he wanted to be involved.

    Through the UDN, Bernstein has access to far more diagnostic tools—and more freedom to use them—than he has in a standard clinic, where patients are generally limited to services included in their health plans. Whereas research scientists use techniques under development—such as whole-genome sequencing and RNA sequencing—few clinicians have access to those services and few health plans cover them until the techniques become sufficiently mainstream that their costs decrease.

    When the Millers brought Chase and Carson, Bernstein and the UDN team compared their symptoms with those of known conditions shared in databases among scientists around the world. Whole-genome sequencing was the next step. Exome sequencing shows only the expressed genes—1.5 percent of the genome—whereas whole-genome sequencing covers the regions that control many other processes, including which genes get expressed.

    When the results came back, they showed two mutations that might have an impact—one in the father and one in the mother, both of which the sons had inherited. A paper published in 2016 in the American Journal of Human Genetics had described the mother’s mutation for the first time, introducing MEPAN syndrome (an acronym for mitochondrial enoyl CoA reductase protein-associated neurodegeneration). The symptoms matched those of the brothers, from the inability to speak and movement difficulties to the lesions in the basal ganglia. The mutation hadn’t come up in the boys’ previous exome sequencing possibly because it was discovered so recently and was unlikely to be included in all databases, or because it lay at the boundary of an exon and an intron—DNA that is expressed and that is not.

    The father’s mutation, however, was entirely in the unexpressed (or noncoding) regions of DNA, which explained why it hadn’t shown up during exome sequencing. Though his mutation had never been described in the scientific literature, it lay within a region that was predicted to regulate the same gene affected by the mother’s mutation: the MECR gene, which is involved in producing mitochondrial fatty acids in humans.

    In both Carson and Chase, the MECR gene from their mother didn’t function. The Stanford team established that the MECR gene from their father—though intact—wasn’t expressed. Since each parent carried one functioning copy of the gene, neither of them had MEPAN. There was a 50 percent chance that each parent would pass on his or her single mutation, and a 25 percent chance that a child would receive the mutations from both parents. Carson and Chase, despite the odds, had each received the two mutations. The result was that mitochondria—the parts of cells that produce energy—functioned poorly.

    For the Millers, the boys’ symptoms suddenly made sense. The brain, though it constitutes only 2 percent of the body’s weight, uses approximately 20 percent of its energy. And the basal ganglia—because it controls motor functions—is one of its most energy-intensive regions. Since Carson and Chase had a genetic mitochondrial disease, this area was most affected, resulting in severe impairment of movement.

    Through the UDN, the Millers were put in contact with other families with MEPAN.

    “With rare diseases,” Miller says, “building community is really important—connecting with the other families.”

    He acknowledges how scary it was to find out that their sons have a rare genetic condition with no proven treatments, but he was relieved to know what they faced. “It allowed us to turn the page and write the next chapter: connect with other MEPAN families, figure out who the researchers are that can help discover treatments.”

    2

    Though only seven patients had been identified worldwide, the families were able to compare notes on potential treatments and how the disease might progress. The oldest known patient, Mike Cohn, lived in Minnesota. He had gone decades without a diagnosis and was an exemplar of how a person could embrace life with a disability. He was 50, had a master’s in education and ran not only a nonprofit to create awareness around disabilities but also his own dance company.

    Carson is almost 9 and Chase is 6, and both lead active lives. “Even though they can’t talk, they’re very vocal in the morning,” Miller says. “They just make noises and let us know that they’re up.”

    Neither of them can crawl, but Chase can climb out of bed and roll down the hallway to the kitchen, whereas Carson can roll only a little. Their parents bathe them, feed them and take them to school, where each has a one-on-one aide who serves as their hands and voice. Miller remarks that the boys are often joking and almost always smiling, though once, a few months ago, with a speech therapist, Carson wrote, “I hate my wheelchair.”

    To communicate, the boys use assistive technology: an iPad for Chase and a speech-generating device with an eye tracker for Carson, whose motor skills were further limited after a brain infection. They have tried VR headsets and like watching YouTube videos of people playing Minecraft or Grand Theft Auto. Chase enjoys exploring the outdoors with his father and roughhousing, whereas Carson would often prefer to be inside reading or watching TV. Carson has also become fascinated by the science of how the body works and watches videos about everything from digestion to reproduction. And he loves Harry Potter.

    “At the very end of the night, as he’s falling asleep,” Miller says, “I read him Harry Potter. We’re reading Harry Potter and the Order of the Phoenix right now, and we’re on like page 690. It’s supposed to be when he’s winding down, and as you’re reading the part where Harry is about to do battle with Voldemort, he gets very excited and animated.”

    Euan Ashley is one of the four principal investigators at Stanford’s Center for Undiagnosed Diseases and served as the first national co-chair of the UDN. Originally from Scotland, Ashley studied physiology and medicine at the University of Glasgow before earning a PhD in genetics from Oxford. He came to Stanford in 2002 as a cardiology fellow, joined the faculty in 2006, and is now a professor of medicine, of genetics and of biomedical data science. As he increasingly focused on precision medicine—which typically involves treating patients according to the genetics of their disease—he heard about the UDN. The National Institutes of Health had started the first center in Bethesda, Md., and, after its initial success, was partnering with academic medical centers. Ashley liked the idea of treating everyone regardless of their ability to pay, and he saw the central role of genetics in diagnostics. He applied alongside the Stanford scientists who would become the other principal investigators at the Center for Undiagnosed Diseases: Bernstein; Paul Fisher, ’84, a professor and pediatric neurologist; and Matthew Wheeler, an assistant professor and fellow cardiologist.

    A 2018 study conducted by UDN-affiliated researchers and published in the New England Journal of Medicine confirmed the power of the UDN model to shorten a patient’s diagnostic odyssey. Prior to being accepted by the UDN, in a small group of patients for whom data was available, the cumulative cost of health care was, on average, $305,428. A UDN evaluation leading to diagnosis averaged $18,903.

    Ashley attributes the UDN’s efficiency in part to its frequent practice of performing immediate exome or whole-genome sequencing, which can identify a syndrome and obviate visits to a merry-go-round of specialists, who may repeat expensive tests or MRIs. “These patients often go and get the same tests in a new place,” Ashley says. “One of the reasons I think the network is so successful is because it’s much more integrated than our normal health-care system. The key part of the approach for the UDN is that we integrate all the opinions and then find the right person who has seen something like this before.”

    The story of Lauren Wong illustrates how long the quest for an answer can be and how quickly it can be resolved. She and her fraternal twin, Nathanial, were born prematurely in 2015. Whereas Nathanial spent a day in the newborn intensive care unit, Lauren, who was much smaller, remained for more than two weeks. Afterward, as the twins grew up, their parents, Mary and Craig Wong, noticed that Lauren wasn’t developing as quickly. A neurologist diagnosed cerebral palsy, but as the months passed, more and more problems presented themselves. Lauren had little appetite. She developed infantile spasms, resulting in numerous, barely perceptible seizures each day. By the time she was 4, she was cognitively at the level of a 5-month-old and physically at the level of an 8-month-old. Eventually, the family’s neurologist ruled out CP and other known conditions. He requested exome sequencing several times, but the Wongs’ health insurance refused the cost.

    3
    COMMUNITY: About 50 children, most of them girls, have the same mutation as Lauren. Her family can now turn to others for advice.

    “When you don’t know,” Mary Wong says of the family’s search for a diagnosis as she tries not to cry, “you feel alone in the world. And you’re just uncertain of what to do next.”

    Every two hours, Lauren is fed via a tube in her stomach, since she doesn’t eat on her own. She receives physical and occupational therapy, as well as vision and speech services. During the day, Lauren attends a special class with a one-to-one aide to support her.

    “She’s a really good kid,” Mary says. “She’s always smiling. She’s never unhappy, which is crazy. Any little thing will make her smile, whether it be a toy or something that lights up or her brother walking by.”

    In 2017, Lauren was accepted at the UDN. Craig, Mary, Nathanial and Lauren all had their exomes sequenced. Within a month, the team at the Stanford center found that, unlike the other members of her family, Lauren had a defective copy of a gene called ALG13. This type of mutation was known as de novo—newly created in the embryo from an error during gene replication. The Stanford team informed them that roughly 20 other girls were known to have Lauren’s mutation and symptoms.

    “We were like, ‘Excuse me? Did you just say about 20?’” Mary recalls.

    In fact, the Wongs have learned, 40 to 50 children have the mutation, most of them girls. (Boys with a defective ALG13 are thought to often die before birth.) The oldest girl with the condition was 16. In many of them, the condition was expressed differently. Some were like Lauren. Others were more active. One was able to walk and run.

    “You just don’t know what to do for your child,” Mary says. “When that unknown is there, it’s hard to figure out which way to go. Even with the diagnosis, we’re still not sure where this is going to take us. But at least we have a group of people that have the same diagnosis, and we can go to them for advice.”

    One of Stanford’s first UDN patients, Anahi Villanueva, had a condition that was unknown to science. Shortly after Anahi’s birth in August 2008, her mother, Maria, saw that her daughter was just sleeping—“She didn’t even cry.” The doctors soon realized that Anahi had gone into a coma. She was transferred first to a hospital in Oakland and then, as her condition worsened, to Lucile Packard Children’s Hospital Stanford. Blood tests showed very low pH from high levels of lactic acid and ammonia.

    4
    RARE: Scientists had never before seen Anahi’s condition­, a mitochondrial disorder that affects energy production.

    “That’s the adult human equivalent of having run a marathon,” says Wheeler, the medical director for adults at the Stanford Center for Undiagnosed Diseases. “You get that sort of burning soreness that’s from lactic acid. It could lead to risk of arrhythmia, injury to the brain or death.”

    For days, Anahi received IV fluids until the acidemia subsided and she recovered. In the years that followed, she had similar crises, brought on by overexertion, not eating enough or—most commonly—a virus like the flu. Each time, her blood levels suggested that her body was exerting itself far beyond the norm. “A couple of times when she got really sick,” her mother recalls, “we thought she wouldn’t make it.”

    Though the episodes were caught early and addressed with emergency room visits and IV fluids, the doctors could offer no diagnosis, and yet the symptoms clearly suggested a mitochondrial disorder.

    One of the hallmarks of mitochondrial disorders is lactic acid buildup. When people can’t generate enough energy from the mitochondria, they produce lactic acid through fermentation—a more rapid but less efficient metabolic process. Anahi’s acidemia suggested that she was relying largely on this backup mechanism. Unlike Carson and Chase’s mitochondrial condition, hers allowed her to walk and speak so long as she avoided taxing activities and getting sick.

    When the UDN began accepting patients in 2015, Anahi was 6 years old. She had an MRI, exome sequencing and sequencing of the mitochondrial genome (mitochondria, being descended from bacteria that were incorporated into larger bacteria between 1.7 billion and
    2 billion years ago, have their own set of genes).

    The Stanford UDN team identified a mutation in a gene involved in the creation of ATP synthase, the mitochondrial subunit that makes adenosine triphosphate—or ATP—the molecule responsible for all energy in the human body (people generate their body weight in ATP every day). But the mutation was entirely new, existing nowhere in the scientific literature.

    “It looked like it was in both copies from her mom and her dad,” Bernstein recalls.

    The researchers searched through databases for another patient with a similar mutation, but nothing turned up. Fortuitously, when Wheeler presented Anahi’s case at a meeting of the American Society of Human Genetics, British scientist Robert Taylor—a specialist in mitochondrial diseases—said he had been studying a patient with similar symptoms and a similar but not identical mutation in the same gene.

    The next step involved creating a model organism—in this case, the fruit fly—to study the impact of the genes. First studied by the geneticist Thomas Hunt Morgan in the early 1900s, fruit flies are among the organisms that—thanks to their rapid breeding time and the facility with which they can be handled—have most furthered our current understanding of genetics.

    When a team of UDN researchers at Baylor knocked down the gene—reducing its expression—in fruit flies, no viable flies were born. A partial knockdown of the gene followed, with the researchers reducing expression only in the head. “When you do that,” Wheeler explains, “you get a shrunken-head fly, with a tiny head that’s very slow to develop.” The team then introduced Anahi’s mutation into a fly’s head, which developed with slight problems, confirming that Anahi’s version of the gene was impaired but still functional.

    Anahi was 9 when the scientists at the UDN made the diagnosis of the new mitochondrial disorder. Though she is not as tall as expected for her age and has to manage her effort carefully, she can otherwise live a relatively normal life.

    “She has missed so many days when she’s sick through the years,” Villanueva says of Anahi’s schooling, “so she’s behind a little bit. Sometimes she says she doesn’t like herself. Sometimes she will say, ‘I wish I was dead instead.’ And then at school sometimes kids pick on her because she’s short.”

    When discussing Anahi’s future, Bernstein weighs the factors that may influence the girl’s life. As people get older, their energy reserves—both fat and starch—increase, allowing them to go longer without food. “In mitochondrial diseases, though, there’s a competing thing, which is that the wear and tear on your body’s cells apparently over time causes the conditions to actually get worse, even if the shorter-term reserve may be bigger.”

    Though Anahi has a diagnosis now, she is one of only two people with her condition, and their symptoms and mutations aren’t exactly the same. Unlike for other patients who have found a community and learned how their disease will progress, her future remains unclear.

    Though the UDN largely focuses on diagnosing disease, one of its scientists, Matthew Might, heads up an effort to match rare diseases with potential treatments. Might, who directs the University of Alabama at Birmingham’s Hugh Kaul Precision Medicine Institute, earned his PhD in 2007 in computer science and began his academic career researching cybersecurity. But when he and his wife, Cristina Casanova, had their first son, Bertrand, they discovered that he had a rare unknown disease. In 2014, the New Yorker article “One of a Kind” described their journey to diagnose it. A struggle they faced was that competing scientists, intent on taking credit for discoveries, weren’t sharing data on rare diseases—an obstacle the UDN has tried to solve.

    In the process of educating himself on how to treat his son, Might embarked on his own odyssey, as he calls it. “If you read enough Wikipedia, you can do almost anything these days,” he says. He taught himself so much about pharmaceutical chemistry that he received a second faculty appointment in the subject at the University of Utah. He then joined Harvard’s department of biomedical informatics while working as a strategist at the White House for President Obama’s precision medicine initiative.

    Might was asked to be the UDN’s director of precision medicine so he could scale up what he had done for his son: use algorithms to classify known medicines and determine whether they might be used to treat rare diseases. (In the United States, a rare disease is one that affects fewer than 200,000 Americans, which works out to about the same proportion used in the European Union’s definition: one in 2,000 people.) While the number of already identified rare diseases has surpassed 6,000—affecting approximately 25 million Americans and vastly more people worldwide—few treatments exist for the conditions. To address this, Might’s team has built an artificial intelligence agent.

    “It’s really a logical reasoning engine,” Might says, “and the first data set it digested to be reasoning over was about 30 million published medical abstracts—so essentially every paper ever published in medicine.”

    To harness the power of this engine, those attempting to treat a rare disease first examine how the disease affects the body on the cellular level. As in a factory, if any part of the machinery isn’t working correctly, material will either stop moving, accumulate or be absent. If scientists can determine where blockages or improper levels of substances occur, they can then use the software to search for a compound that might create balance in the system.

    “You can ask it very low-level questions, like ‘What’s an inhibitor for this gene?’” Might says. “Or you can ask it very high-level questions, like ‘What is the potential treatment for this condition?’”

    He often finds himself working with parents who, through their own online research, have become experts just as he has. Danny Miller, the father of Carson and Chase, recently reached out to Might to propose a way that an enzyme missing in MEPAN might be circumvented.

    “We checked it out,” Might says, “and sure enough, it looks like he’s right.”

    The lesson in Might’s work is that previous scientific discoveries can be built on; they aren’t investments for a single individual or disease. This addresses the skepticism of those who see research, diagnosis and treatment of rare diseases as too costly.

    “There is essentially no rare disease,” Evan Ashley says, “that doesn’t have a correlate in common disease. You can have variants in that gene that are common and have a small effect on the function of the gene, or you can have variants that are extremely rare and have a massive effect.”

    He gives the example of how studying hypercholesterolemia—a genetic condition that causes unusually high cholesterol—led to treatment of commonplace cholesterol problems.

    “That gene,” he says, “is now the target of the newest and best drug for cholesterol.”

    And whereas Ashley acknowledges the satisfaction in the “Sherlock Holmes element” of the work, he finds the human element most compelling.

    “Each story is literally an odyssey for a family. What makes it so meaningful is that there’s always a face, there’s a person, a family suffering. If you can solve this case, if you were staying up late at night wading through data, the chances are that if you solve it, you help that person and another 10 families with the same condition.”

    5
    IN LIMBO: Doctors suspect Miguel has multiple syndromes.

    For many families, the odyssey that the UDN’s doctors speak of is ongoing and may last for years. Genetic and patient databases are constantly updated, allowing scientists to find new matches, but the wait can be torturous, as it has been for Miguel Bejar and Georgina Guerrero.

    Born in 1977, in the small town of Tizapan, in Jalisco, Mexico, Miguel Bejar moved to Redwood City, Calif., when he was 17. After getting his high school diploma, he took a job as housekeeping assistant at Stanford Hospital. Over more than 20 years, he was promoted first to housekeeping lead, then to housekeeping supervisor, and then transferred to the main operating room, where he is now a lead assistant.

    After he married Guerrero, a dentist’s assistant from Michoacán, they waited more than four years, preparing their home and finances, before starting a family. Their son, Miguel, was born in April 2015. The pregnancy was healthy, though a doctor detected a heart murmur shortly after birth. “He told me that’s pretty normal in babies when they are newborns, and usually it will go away in two or three days,” Bejar recalls.

    But an echocardiogram showed a deformation of the aortic valve and a narrowing of the aorta, which limited blood flow. Doctors successfully performed heart surgery, but three months later, crystals appeared in Miguel’s urine, gathering in his diapers. Further medical tests showed that his red blood cells were slightly smaller than normal, and a genetic test immediately revealed that he had 8p23.1 duplication syndrome—a rare chromosomal anomaly in which the short arm of chromosome 8 is partially duplicated.

    Bejar recalls the doctors explaining the syndrome. “They told me that there were 17 known cases and the syndrome in those situations behaved differently. But they all have cardiac issues.”

    The syndrome, however, didn’t explain all of the symptoms Miguel would soon have. He began growing too quickly—his head even more rapidly than his body. In January 2018, his head’s circumference was 21.8 inches. By October, it was 22. By May 2019, it was 22.4. An MRI showed that his brain was underdeveloped and had large white ventricles. He was soon diagnosed with autism, and his muscles were weak. He walked poorly, fell easily and hadn’t learned to speak. He had kidney stones and would soon need more heart surgery. At the age of 4, he is the size of a 7-year-old, and his head has now surpassed 22.6 inches—almost as big as his father’s.

    “I was a little blessed by having the job at Stanford and having access to doctors,” Bejar recalls. “Without this place, I can’t imagine how other families . . . I mean, for me it has been a little hard. For other families,
    I believe it’s harder.”

    In early 2018, he applied to the UDN, and Miguel was accepted within weeks. The team assigned to Miguel is sequencing the DNA from both his blood and his skin to compare them to determine whether he has mosaicism—a condition in which genetic mutations occur early during development and present only in certain tissues. The team is looking for multiple syndromes, which Bernstein says can be especially challenging: “One condition can mask or confuse you about what’s going on with the other one.”

    As for the next step, that will depend on what current tests reveal—if anything—and what the team decides once it has reviewed the data. After all, more often than not, the UDN does not come up with diagnoses or must wait to connect patients on file to new findings in the scientific literature. Its success rate to date hovers around 28 percent, which means hundreds of people continue to live in limbo.

    While Bejar awaits the results, he tries to reconcile the pain of uncertainty with the tenderness he feels for his son.

    “If I had the opportunity to be a father and this happens again,” he says, “I will take it because it’s one of the best experiences, taking care of a child with necessities. It brings the best out of your human side. You go beyond a lot of your limits on the way you love life, and the way you appreciate life and people.”

    See the full article here .


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  • richardmitnick 12:47 pm on September 4, 2019 Permalink | Reply
    Tags: , Building the new soft electronics will require a new class of materials that exhibits high conductivity while also remaining chemically and mechanically compatible with the host matrix., Medicine, , Soft nanoelectronic composites are critical to advancing fields such as wearable devices; soft robotics; and personalized healthcare., The conductive protein nanowires exhibit highly tunable conductivity while remaining significantly softer than carbon nanotubes or noble metals such as gold., The new devices will use conductive protein nanowires-or pili- that will function as the conductive element of the protein-based soft electronics., The scientists plan to use conductive protein nanowires and mechanically soft nanomaterials to create a new nanocomposite that is strong flexible and highly conductive., They disperse evenly in water while nanotubes and metals clump together.,   

    From UMass Amherst: “UMass Amherst Researchers Awarded $1.75-million in NSF Funding to Study and Develop New Class of Soft Electronics” 

    U Mass Amherst

    From UMass Amherst

    September 4, 2019
    Stephen S. Nonnenmann
    ssn@engin.umass.edu
    413-545-4051

    1
    Soft stretchable electronic device

    New devices will exhibit both flexibility and high conductivity.

    A team of researchers at the University of Massachusetts Amherst has received a four-year, $1.75 million grant from the National Science Foundation (NSF) to study and construct soft stretchable electronic devices that can be used in future healthcare, security and communications applications.

    The scientists plan to use conductive protein nanowires and mechanically soft nanomaterials to create a new nanocomposite that is strong, flexible and highly conductive.

    The interdisciplinary research team is led by Stephen S. Nonnennman, associate professor of mechanical and industrial engineering, and includes Todd S. Emrick, professor of polymer science and engineering, Derek R. Lovley, Distinguished Professor of microbiology, and Jessica D. Schiffman, associate professor of chemical engineering. All four faculty members are affiliated with the Institute of Applied Life Sciences (IALS), which combines deep and interdisciplinary expertise from 29 departments on the UMass Amherst campus to translate fundamental research into innovations that benefit humankind.

    Soft nanoelectronic composites are critical to advancing fields such as wearable devices, soft robotics, and personalized healthcare. “The conductive protein nanowires exhibit highly tunable conductivity while remaining significantly softer than carbon nanotubes or noble metals such as gold,” says Nonnenmann. “The second key point is that they disperse evenly in water, while nanotubes and metals clump together. These two factors really make pili-polymer nanocomposite pairings particularly exciting to explore and manufacture.”

    The NSF Designing Materials to Revolutionize and Engineer our Future (DMREF) program is related to the national Materials Genome Initiative (MGI) which aims to “deploy advanced materials at least twice as fast as possible today, at a fraction of the cost.” MGI integrates experimental materials discovery with computational design. The DMREF team also includes Arthi Jayaraman, professor of chemical engineering and materials science at the University of Delaware, a world-renowned authority on computational studies of molecular-level phenomena. Together, their work “has the potential to bring the U.S. to the forefront of flexible electronics development, while training the next generation workforce to maintain this competitive advantage.”

    Building the new soft electronics will require a new class of materials that exhibits high conductivity while also remaining chemically and mechanically compatible with the host matrix. Current stretchable electronics use thin, hard and brittle conductive materials such as metal nanowires or carbon nanotubes embedded in stretchable elastic polymers, but they often fail because of the mechanical mismatch between the materials. The new devices will use conductive protein nanowires, or pili, that will function as the conductive element of the protein-based soft electronics.

    The team will leverage their collective expertise to design and develop protein nanowire-matrix pairings that are both highly functional and easily manufactured. Development of such structures will pair molecular modeling (Jayaraman) with synthetic biology (Lovley) to determine amino acid sequences that not only provide conductivity, but also anchor points to integrate into the polymer matrices (Emrick) and flexible fabrics (Schiffman) developed in parallel. Nonnenmann will evaluate their electronic-mechanical functionality using advanced microscopy and transport methods, thus forming a computational-synthetic-experimental feedback loop across the team. The goal of advantageously combining new synthetic polymers with these biologically derived protein nanowires is both intellectually challenging and vital to making advances in this bioelectronics field.

    See the full article here .

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    U Mass Amherst campus

    UMass Amherst, the Commonwealth’s flagship campus, is a nationally ranked public research university offering a full range of undergraduate, graduate and professional degrees.

    As the flagship campus of America’s education state, the University of Massachusetts Amherst is the leader of the public higher education system of the Commonwealth, making a profound, transformative impact to the common good. Founded in 1863, we are the largest public research university in New England, distinguished by the excellence and breadth of our academic, research and community outreach programs. We rank 29th among the nation’s top public universities, moving up 11 spots in the past two years in the U.S. News & World Report’s annual college guide.

     
  • richardmitnick 12:01 pm on September 4, 2019 Permalink | Reply
    Tags: , “This study demonstrates how mechanical perturbations of an implant can modulate the host foreign body response...", DSR-dynamic soft reservoir, Implantable medical devices have various failure rates that can be attributed to fibrosis ranging from 30-50 percent for implantable pacemakers or 30 percent for mammoplasty prosthetics., Medicine, , Soft robotics, Soft robots are flexible devices that can be implanted into the body., The research describes the use of soft robotics to modify the body’s response to implanted devices., These complex and unpredictable foreign-body responses impair device function and drastically limit the long-term performance and therapeutic efficacy of these devices., These implanted devices are not without problems caused in part by the body’s own protection responses., This work could help patients requiring in-situ (implanted) medical devices such as breast implants; pacemakers; neural probes; glucose biosensors; and drug and cell delivery devices.   

    From MIT News: “Soft robotics breakthrough manages immune response for implanted devices” 

    MIT News

    From MIT News

    September 4, 2019
    Institute for Medical Engineering and Science

    1
    Depiction of a soft robotic device known as a dynamic soft reservoir (DSR) Image courtesy of the researchers.

    Discovery could enable longer-lasting and better-functioning devices — including pacemakers, breast implants, biosensors, and drug delivery devices.

    Researchers from the Institute for Medical Engineering and Science (IMES) at MIT; the National University of Ireland Galway (NUI Galway); and AMBER, the SFI Research Centre for Advanced Materials and BioEngineering Research, recently announced a significant breakthrough in soft robotics that could help patients requiring in-situ (implanted) medical devices such as breast implants, pacemakers, neural probes, glucose biosensors, and drug and cell delivery devices.

    The implantable medical devices market is currently estimated at approximately $100 billion, with significant growth potential into the future as new technologies for drug delivery and health monitoring are developed. These devices are not without problems, caused in part by the body’s own protection responses. These complex and unpredictable foreign-body responses impair device function and drastically limit the long-term performance and therapeutic efficacy of these devices.

    One such foreign body response is fibrosis, a process whereby a dense fibrous capsule surrounds the implanted device, which can cause device failure or impede its function. Implantable medical devices have various failure rates that can be attributed to fibrosis, ranging from 30-50 percent for implantable pacemakers or 30 percent for mammoplasty prosthetics. In the case of biosensors or drug/cell delivery devices, the dense fibrous capsule which can build up around the implanted device can seriously impede its function, with consequences for the patient and costs to the health care system.

    A radical new vision for medical devices to address this problem was published in the internationally respected journal, Science Robotics. The study was led by researchers from NUI Galway, IMES, and the SFI research center AMBER, among others. The research describes the use of soft robotics to modify the body’s response to implanted devices. Soft robots are flexible devices that can be implanted into the body.

    The transatlantic partnership of scientists has created a tiny, mechanically actuated soft robotic device known as a dynamic soft reservoir (DSR) that has been shown to significantly reduce the build-up of the fibrous capsule by manipulating the environment at the interface between the device and the body. The device uses mechanical oscillation to modulate how cells respond around the implant. In a bio-inspired design, the DSR can change its shape at a microscope scale through an actuating membrane.

    IMES core faculty member, assistant professor at the Department of Mechanical Engineering, and W.M. Keck Career Development Professor in Biomedical Engineering Ellen Roche, the senior co-author of the study, is a former researcher at NUI Galway who won international acclaim in 2017 for her work in creating a soft robotic sleeve to help patients with heart failure. Of this research, Roche says “This study demonstrates how mechanical perturbations of an implant can modulate the host foreign body response. This has vast potential for a range of clinical applications and will hopefully lead to many future collaborative studies between our teams.”

    Garry Duffy, professor in anatomy at NUI Galway and AMBER principal investigator, and a senior co-author of the study, adds “We feel the ideas described in this paper could transform future medical devices and how they interact with the body. We are very excited to develop this technology further and to partner with people interested in the potential of soft robotics to better integrate devices for longer use and superior patient outcomes. It’s fantastic to build and continue the collaboration with the Dolan and Roche labs, and to develop a trans-Atlantic network of soft roboticists.”

    The first author of the study, Eimear Dolan, lecturer of biomedical engineering at NUI Galway and former researcher in the Roche and Duffy labs at MIT and NUI Galway, says “We are very excited to publish this study, as it describes an innovative approach to modulate the foreign-body response using soft robotics. I recently received a Science Foundation Ireland Royal Society University Research Fellowship to bring this technology forward with a focus on Type 1 diabetes. It is a privilege to work with such a talented multi-disciplinary team, and I look forward to continuing working together.”

    See the full article here .


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    Please help promote STEM in your local schools.


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    MIT Seal

    The mission of MIT is to advance knowledge and educate students in science, technology, and other areas of scholarship that will best serve the nation and the world in the twenty-first century. We seek to develop in each member of the MIT community the ability and passion to work wisely, creatively, and effectively for the betterment of humankind.

    MIT Campus

     
  • richardmitnick 9:17 am on August 26, 2019 Permalink | Reply
    Tags: "The New Black Bag", , Harvard Medicine, Medicine   

    From Harvard University Medicine: “The New Black Bag” 


    From Harvard University Medicine

    8.26.19
    Jessica Cerretani

    Many are flummoxed over how to improve health care delivery. But for some doctors, the answer is clear—meet patients where they are.

    7

    It’s a sweltering summer morning outside Dallas, and the doctor’s bag weighs heavy as the physician stands on the porch, waiting for the door to open. When it does, she’s greeted with wide smiles from her three young patients and their mother. They welcome her inside, hand her a glass of water, and clear a place at the table. Over the next two hours, the pediatrician checks the children’s vitals, conducts physical exams, and writes any necessary prescriptions. She catches up with the family, too, listening intently to the details of their lives and plans for the coming school year. When she departs, the goodbyes are like those to an old friend.

    1
    Tonya McDonald

    Today, such a scenario seems quaint. But for Tonya McDonald, MD ’98, it’s business as usual. This past spring, she opened Radiance Pediatrics, a direct primary care practice that provides in-home and virtual pediatric care to families who pay a flat monthly fee. For this fee, families get extended visits, same- or next-day appointments, telemedicine visits, and direct access to McDonald through phone, text, and email.

    “In some ways, this is a throwback, an old-school approach to medicine,” she admits. “But it gives me the opportunity to help rebuild the doctor-patient relationship. It’s a gift to be able to truly bond with families.”

    Not long ago, McDonald was part of the 78 percent of U.S. physicians struggling to cope with burnout, a problem some have labeled a public health crisis.

    “In the past five years, I was seeing up to thirty children a day, feeling sad that I couldn’t practice medicine the way I wanted,” McDonald says. “Insurance dictated what I could do.”

    McDonald knew it was time for a change. And she’s far from alone.

    “People point to our salaries as an issue,” says Rushika Fernandopulle, MD ’94, “but the real problem is that the job of primary care itself can be awful. Until we fix that, no amount of money will matter.”

    5
    Rushika Fernandopulle

    For Fernandopulle, founder and CEO of team-based primary care provider Iora Health, that means rebuilding the field.

    “Imagine that it’s 1902 and we want to get from Boston to London in a day and all we have are ships,” he muses. “We need a plane, but you can’t just slap wings on a ship.”

    “Incremental change hasn’t worked,” he adds.

    Then, like McDonald and others working in primary care today, Fernandopulle gets to the heart of the matter, “Let’s stop making excuses and build what we know primary care should be.”

    Patients’ voices

    Even as physicians like McDonald and Fernandopulle find themselves at the forefront of an evolving field, they acknowledge that much of the transformation in primary care is being driven by patients themselves. Dissatisfied with long waits, short appointments, and inadequate access to physicians, patients are voting with their feet and increasingly moving their care to models that prioritize wellness, relationships, and continuity.

    Giving patients a voice—and listening to that voice—might seem faddish, but for some physicians, this has been the norm for decades. It’s an approach that James O’Connell, MD ’82, learned early in his career working with Boston’s homeless population.

    As the first doctor for the nonprofit Boston Health Care for the Homeless Program, O’Connell quickly discovered that many of the qualities he was taught to value, like speed and efficiency, had to be tossed out the window. To gain his patients’ trust and respect, O’Connell needed to meet them where they were—usually literally—and establish solid relationships.

    “This population hated people like me, who were there to ‘do good’ for a year and move on,” he says. “They wanted what we all look for in a doctor: Someone to form a relationship with over time.”

    3
    James O’Connell

    Nearly four decades later, O’Connell says his patients continue to drive the conversation about what primary care means, whether that’s being on call for late-night visits on the street or ensuring continuity of services after a patient receives housing. For the men and women O’Connell sees, these are needs born of the realities of living on the street. In some ways, those needs mirror the shortfalls of primary care as a whole.
    James O’Connell

    “The homeless population will show you the weaknesses in the traditional health care system without even trying,” he says. “They continue to teach us how we’ve been doing things wrong.”

    Giving patients a say in care delivery is also integral to Sonya Shin’s work with the Navajo Nation. Shin, MD ’98, is an HMS associate professor of medicine at Brigham and Women’s Hospital and the director of Community Outreach and Patient Empowerment (COPE), which is part of a joint tribal–Indian Health Services effort to address health disparities in the Navajo Nation. In the decade since its inception, COPE has strengthened relationships between physicians and community health representatives (CHRs), who are public health workers and members of the Navajo Nation community. COPE has also created a team approach to primary care for its patients, many of whom live in poverty and have diagnoses of chronic conditions such as diabetes and cardiovascular disease.

    __________________________________________________
    Enhanced interaction between clinicians and CHRs may be linked to better outcomes in patients.
    __________________________________________________

    The citizen-patients of Navajo Nation aren’t afraid to voice their opinions about health care, and they have the means for doing so. A number of programs, including patient and family advisory councils, allow patients to meet with tribal elders, executive leadership, and clinicians to advocate for quality care. Their insight, says Shin, has helped improve communication between physicians and CHRs.

    “It takes a lot of time to work with the community and build trust; we can’t just give lip service to their needs,” she explains. “Our providers are grateful for the patients who have really thought about the changes that need to be made in care delivery.”

    Group practice

    Making primary care a team-based endeavor is one significant change.

    In the Navajo Nation, where patients with chronic diseases may see a physician only every six to 12 months, CHRs have been a critical part of primary care delivery since the 1960s. There had been, however, a disconnect when it came to ensuring that physicians and CHRs were keeping each other in the loop regarding patients’ health.

    “Doctors work at hospitals; CHRs work within the community,” says Shin. “They were practicing in separate spheres.”

    __________________________________________________
    “The homeless population will show you the weaknesses in the traditional health care system without even trying,” he says. “They continue to teach us how we’ve been doing things wrong.”
    __________________________________________________

    To address this disconnect, Shin and her colleagues at COPE began mapping the care process, implementing electronic health records for referral and CHR documentation, and creating teaching materials to train physicians and CHRs to work together for patients.

    The approach has paid off. A 2017 study published in BMC Public Health found that more than 80 percent of CHRs felt strongly that COPE trainings were useful, while nearly 45 percent believed that communication and teamwork had improved because of COPE’s initiatives. What’s more, early data suggest that enhanced interaction between clinicians and CHRs may be linked to better outcomes in patients, including improved lipid profiles and A1c values.

    CHRs and health coaches also play an important role in primary care at Fernandopulle’s Iora Health. At the provider’s practices throughout the United States, patients receive care not only from a physician but also from a team of professionals that includes community-based health coaches, behavioral health specialists, social workers, and nurses. According to Fernandopulle, patients who visit an Iora practice—intentionally kept small and situated in accessible locations such as strip malls—are met by a dedicated greeter before being seen by all members of their core health care team in one visit. After a patient visits, the team huddles and discusses next steps for helping that patient achieve their health and wellness goals. That might mean providing clinical advice, involving a support group, or recommending specialty care.

    “We can’t just tell patients what to do,” says Fernandopulle. “We need to help them develop a plan and execute it.”

    At Iora, health coaches perform outreach, working with patients in their community to improve adherence to treatment and address such social determinants of health as access to healthy food, safe public spaces, transportation, and other environmental factors that influence health and perpetuate health inequities.

    Fernandopulle recalls an older woman who had moved to a new city and lacked a car. Worried about being a burden on her family, she isolated herself by staying at home, and she became sedentary, which worsened her diabetes.

    In an Iora team huddle, her physician asked if she needed a higher dose of medication.

    “No,” her coach replied, “she needs to get more engaged.”

    3
    Elizabeth Kwo

    Her coach taught the patient how to take public transportation and encouraged her to join a local social group. With time, her blood-sugar levels improved.

    Such results are impressive to clinicians but not necessarily to insurance companies in the traditional fee-for-service system. “There’s no CPT code for ‘teach patient to ride the bus,’” Fernandopulle says ruefully. “So in most practices, no one thinks of doing this—even if it’s the right thing to do.”

    People power

    By placing primary care at the top of the funnel, Fernandopulle hopes that Iora will shift the current specialty-driven power dynamic in medicine.

    “We think that primary care is the best platform for fixing health care as a whole because it’s closest to the consumer,” he says. “We can help patients upstream by encouraging them to eat better and exercise and downstream by helping them navigate choosing a specialist. When you flip the model, primary care now becomes the center of the health care system.”

    Access to specialists is getting a makeover, too. Traditionally accomplished through referrals and marred by lengthy wait times, seeing a specialist can be fraught with frustration. Companies like InfiniteMD, co-founded by Elizabeth Kwo, MD ’09, who is also the company’s chief medical officer, are seeking to change that, relying on telemedicine to offer patients virtual second-opinion consultations with specialists. The service, available worldwide to people who self-pay or whose employers provide the service, allows patients to video chat with top-ranked oncologists, neurologists, pediatricians, and other specialists.

    “Physicians don’t have the capacity to see hundreds of patients a day, but you can streamline that process by having patient coordinators work with patients to review their records and help them winnow their concerns to just five questions,” says Kwo. By paying specialists for their time directly, the company moves its customers to the front of the line, giving them the opportunity to gain medical insights quickly.

    “Getting specialists to weigh in on complicated cases can be really helpful for patients and for community doctors,” she says. “We’ve had cases where our specialists have led people to better treatment or helped them access clinical trials.”

    Support systems

    Any changes in health care delivery generate the question of who pays. For now, the answer depends on the model—and the differences can be notable.

    The model that O’Connell describes is “the other side of concierge medicine.” That means allowing for an on-call, no-appointment system in which a clinician’s hospital affiliation automatically makes homeless people patients of that clinician’s hospital, even if they never set foot inside it. About three-quarters of the caregiving costs for patients of Boston Health Care for the Homeless are covered by Medicaid, with the remainder coming from grants and philanthropic support.
    Rushika Fernandopulle

    “When people live on the streets, they end up subjugating their health care needs to simply trying to stay alive,” O’Connell says. “They come to the emergency department when they’re very sick. If we want to provide ongoing care of chronic diseases, we need to go to them.”

    Iora Health partners with companies to make its services available to employees; Medicare Advantage patients also make up a large portion of its population. But it began as essentially a direct-care model, in which people pay about $40 a month for team-based primary care services. “The current health care system is all about transactions, but when did transactions ever heal people?” says Fernandopulle. “We want to stop the madness of fee-for-service reimbursement and the games that go with that.”

    Radiance Pediatrics is also a direct-care model but one that eschews insurance altogether. McDonald does, however, encourage parents to carry some form of coverage, such as catastrophic insurance. Families pay a per-child monthly fee, ranging from $75 to $125 depending on the age and number of children.
    “It’s reasonable over the long term if parents are self-employed and their kids have chronic health issues,” she says.

    It’s a harder sell for families who need only an annual well-child visit, but McDonald says she also sees families who are insured yet willing to pay out of pocket for her availability and the convenience of house calls. Her practice also appeals to members of health-sharing ministries, organizations in which members with similar religious or ethical beliefs share health care costs. Such ministries often don’t cover well-child care.

    “This isn’t necessarily the right approach for everyone, but it’s one way that we can try to reclaim primary care,” says McDonald. “Good health care shouldn’t be about dollars and cents. It should be about our relationships with patients—which is why we got into medicine in the first place.”

    See the full article here .

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    Harvard University campus
    Harvard is the oldest institution of higher education in the United States, established in 1636 by vote of the Great and General Court of the Massachusetts Bay Colony. It was named after the College’s first benefactor, the young minister John Harvard of Charlestown, who upon his death in 1638 left his library and half his estate to the institution. A statue of John Harvard stands today in front of University Hall in Harvard Yard, and is perhaps the University’s best known landmark.

    Harvard University has 12 degree-granting Schools in addition to the Radcliffe Institute for Advanced Study. The University has grown from nine students with a single master to an enrollment of more than 20,000 degree candidates including undergraduate, graduate, and professional students. There are more than 360,000 living alumni in the U.S. and over 190 other countries.

     
  • richardmitnick 8:54 am on August 17, 2019 Permalink | Reply
    Tags: "Wireless sensors that stick to the skin to track our health", , , Medicine, Stanford engineers have developed a way to detect physiological signals emanating from the skin with sensors that stick like band-aids and beam wireless readings to a receiver clipped onto clothing., , The BodyNet sticker, The researchers had to create an antenna that could stretch and bend like skin.   

    From Stanford University: “Wireless sensors that stick to the skin to track our health” 

    Stanford University Name
    From Stanford University

    August 16, 2019
    Tom Abate
    (650) 736-2245
    tabate@stanford.edu

    1
    The rubber sticker attached to the wrist can bend and stretch as the person’s skin moves, beaming pulse readings to a receiver clipped to the person’s clothing. (Image credit: Bao Lab)

    We tend to take our skin’s protective function for granted, ignoring its other roles in signaling subtleties like a fluttering heart or a flush of embarrassment.

    2
    Using metallic ink, researchers screen-print an antenna and sensor onto a stretchable sticker designed to adhere to skin and track pulse and other health indicators, and beam these readings to a receiver on a person’s clothing. (Image credit: Bao Lab)

    Now, Stanford engineers have developed a way to detect physiological signals emanating from the skin with sensors that stick like band-aids and beam wireless readings to a receiver clipped onto clothing.

    To demonstrate this wearable technology, the researchers stuck sensors to the wrist and abdomen of one test subject to monitor the person’s pulse and respiration by detecting how their skin stretched and contracted with each heartbeat or breath. Likewise, stickers on the person’s elbows and knees tracked arm and leg motions by gauging the minute tightening or relaxation of the skin each time the corresponding muscle flexed.

    Zhenan Bao, the chemical engineering professor whose lab described the system in an Aug. 15 article in Nature Electronics, thinks this wearable technology, which they call BodyNet, will first be used in medical settings such as monitoring patients with sleep disorders or heart conditions. Her lab is already trying to develop new stickers to sense sweat and other secretions to track variables such as body temperature and stress. Her ultimate goal is to create an array of wireless sensors that stick to the skin and work in conjunction with smart clothing to more accurately track a wider variety of health indicators than the smart phones or watches consumers use today.

    “We think one day it will be possible to create a full-body skin-sensor array to collect physiological data without interfering with a person’s normal behavior,” said Bao, who is also the K.K. Lee Professor in the School of Engineering.

    Stretchable, comfortable, functional

    Postdoctoral scholars Simiao Niu and Naoji Matsuhisa led the 14-person team that spent three years designing the sensors. Their goal was to develop a technology that would be comfortable to wear and have no batteries or rigid circuits to prevent the stickers from stretching and contracting with the skin.

    Their eventual design met these parameters with a variation of the RFID – radiofrequency identification – technology used to control keyless entry to locked rooms. When a person holds an ID card up to an RFID receiver, an antenna in the ID card harvests a tiny bit of RFID energy from the receiver and uses this to generate a code that it then beams back to the receiver.

    The BodyNet sticker is similar to the ID card: It has an antenna that harvests a bit of the incoming RFID energy from a receiver on the clothing to power its sensors. It then takes readings from the skin and beams them back to the nearby receiver.

    But to make the wireless sticker work, the researchers had to create an antenna that could stretch and bend like skin. They did this by screen-printing metallic ink on a rubber sticker. However, whenever the antenna bent or stretched, those movements made its signal too weak and unstable to be useful.

    To get around this problem, the Stanford researchers developed a new type of RFID system that could beam strong and accurate signals to the receiver despite constant fluctuations. The battery-powered receiver then uses Bluetooth to periodically upload data from the stickers to a smartphone, computer or other permanent storage system.

    The initial version of the stickers relied on tiny motion sensors to take respiration and pulse readings. The researchers are now studying how to integrate sweat, temperature and other sensors into their antenna systems.

    To move their technology beyond clinical applications and into consumer-friendly devices, the researchers need to overcome another challenge – keeping the sensor and receiver close to each other. In their experiments, the researchers clipped a receiver on clothing just above each sensor. One-to-one pairings of sensors and receivers would be fine in medical monitoring, but to create a BodyNet that someone could wear while exercising, antennas would have to be woven into clothing to receive and transmit signals no matter where a person sticks a sensor.

    Bao is also a senior fellow of the Precourt Institute for Energy, a member of Stanford Bio-X, a faculty fellow of Stanford ChEM-H, an affiliate of the Stanford Woods Institute for the Environment and a member of the Wu Tsai Neurosciences Institute. Other Stanford co-authors are Jeffrey B.-H. Tok, research scientist; Ada Poon, associate professor of electrical engineering; William Burnett, adjunct professor of mechanical engineering; postdoctoral scholars Yuanwen Jiang and Jinxing Li; graduate student Jiechen Wang; and former visiting scholar Youngjun Yun and former postdoctoral scholars Sihong Wang, Xuzhou Yan and Levent Beker. Researchers from Singapore’s Nanyang Technological University also co-authored the study.

    This research was supported by Samsung Electronics; the Singapore Agency for Science, Technology and Research; the Japan Society for the Promotion of Science; and the Stanford Precision Health and Integrated Diagnosis Center.

    See the full article here .


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    Stanford University campus. No image credit

    Stanford University

    Leland and Jane Stanford founded the University to “promote the public welfare by exercising an influence on behalf of humanity and civilization.” Stanford opened its doors in 1891, and more than a century later, it remains dedicated to finding solutions to the great challenges of the day and to preparing our students for leadership in today’s complex world. Stanford, is an American private research university located in Stanford, California on an 8,180-acre (3,310 ha) campus near Palo Alto. Since 1952, more than 54 Stanford faculty, staff, and alumni have won the Nobel Prize, including 19 current faculty members

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  • richardmitnick 7:45 am on August 13, 2019 Permalink | Reply
    Tags: "Ebola Is Now Curable. Here’s How the New Treatments Work", , , , , Medicine   

    From WIRED: “Ebola Is Now Curable. Here’s How the New Treatments Work” 

    Wired logo

    From WIRED

    08.12.19
    Megan Molteni

    1
    A clinical trial in the Democratic Republic of Congo has been testing new Ebola drugs with dramatic results. For newly infected patients on one of the drugs, the mortality rate dropped to 6 percent.

    Amid unrelenting chaos and violence, scientists and doctors in the Democratic Republic of Congo have been running a clinical trial of new drugs to try to combat a year-long Ebola outbreak. On Monday, the trial’s cosponsors at the World Health Organization and the National Institutes of Health announced that two of the experimental treatments appear to dramatically boost survival rates.

    While an experimental vaccine previously had been shown to shield people from catching Ebola, the news marks a first for people who already have been infected. “From now on, we will no longer say that Ebola is incurable,” said Jean-Jacques Muyembe, director general of the Institut National de Recherche Biomedicale in the DRC, which has overseen the trial’s operations on the ground.

    Starting last November, patients in four treatment centers in the country’s east, where the outbreak is at its worst, were randomly assigned to receive one of four investigational therapies—either an antiviral drug called remdesivir or one of three drugs that use monoclonal antibodies. Scientists concocted these big, Y-shaped proteins to recognize the specific shapes of invading bacteria and viruses and then recruit immune cells to attack those pathogens. One of these, a drug called ZMapp, is currently considered the standard of care during Ebola outbreaks. It had been tested and used during the devastating Ebola epidemic in West Africa in 2014, and the goal was to see if those other drugs could outperform it. But preliminary data from the first 681 patients (out of a planned 725) showed such strong results that the trial has now been stopped.

    Patients receiving Zmapp in the four trial centers experienced an overall mortality rate of 49 percent, according to Anthony Fauci, director of the NIH’s National Institute of Allergy and Infectious Diseases. (Mortality rates are in excess of 75 percent for infected individuals who don’t seek any form of treatment.) The monoclonal antibody cocktail produced by a company called Regeneron Pharmaceuticals had the biggest impact on lowering death rates, down to 29 percent, while NIAID’s monoclonal antibody, called mAb114, had a mortality rate of 34 percent. The results were most striking for patients who received treatments soon after becoming sick, when their viral loads were still low—death rates dropped to 11 percent with mAb114 and just 6 percent with Regeneron’s drug, compared with 24 percent with ZMapp and 33 percent with Remdesivir.

    Drugs based on monoclonal antibodies have become a mainstay of modern medicine—fending off a variety of diseases from cancer to lupus. But it takes many years of painstaking reverse-engineering to make them. Zmapp, for instance, was developed by infecting mice with Ebola and then collecting the antibodies the mice produced against the virus. Those antibodies then had to be further engineered to look more like a human antibody, so as not to provoke an immune reaction. Ebola infiltrates its victims’ cells using spiky proteins on the virus’s outer shell, so researchers screened the antibodies for the ones that did the best job of binding to those proteins. Block access, and the virus can’t replicate and spread. But compared with other viruses, Ebola is large and has the ability to change shape, making it difficult for any one antibody to block its infection. That’s why a cocktail approach has become favored, like the Regeneron product—a combination of three monoclonal antibodies generated first in mice.

    An even better solution, some have posited, would be to mine the serum of Ebola survivors and harvest the DNA from the white blood cells that make antibodies. That would yield a set of genetic instructions for making antibodies with a proven track record against the Ebola virus. That’s what the NIH’s mAb114 is—an antibody isolated from the blood of a survivor of a 1995 outbreak in Kikwit, DRC. Scientists discovered it a few years ago—they had been circulating in his body for more than a decade.

    With the WHO’s announcement a new trial will now kick off, directly comparing Regeneron to mAb114, which is being produced by a Florida-based company called Ridgeback Biotherapeutics. And all Ebola treatment units in the outbreak zone will now only administer the two most effective monoclonal antibody drugs, according to the WHO’s director of health emergencies, Mike Ryan.

    “Today’s news puts us one more step to saving more lives,” said Ryan. “The success is clear. But there’s also a tragedy linked to the success. The tragedy is that not enough people are being treated. We are still seeing too many people staying away from treatment centers, people not being found in time to benefit from these therapies.”

    Since the ongoing outbreak began last August in DRC’s North Kivu province, more than 2,800 people have become infected, with 1,794 confirmed deaths. It is the second-largest Ebola outbreak ever recorded. On July 17, the WHO declared it a “public health emergency of international concern,” after a case showed up in Goma, a large city bordering Rwanda. The risk of transmission across international borders remains high.

    See the full article here .

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  • richardmitnick 9:23 am on August 10, 2019 Permalink | Reply
    Tags: After sporadic outbreaks in 2017 and 2018 the DRC is now experiencing the world’s second-largest recorded outbreak., , , , , , , Increased global travel also means there is a greater likelihood that infectious agents particularly airborne pathogens that can produce disease can rapidly spread among the human population., Medicine, Promising novel and repurposed drugs and treatments need to be evaluated in appropriate animal models in laboratories operating under the highest containment (‘Biosafety Level 4’)., Reports out of the region suggest that only half of the cases are being identified and reported., The World Health Organization has declared Ebola a ‘Public Health Emergency of International Concern’ (PHEIC), Vaccination alone cannot solve Ebola., We need to listen to the local leadership and ask them what they need for a community-led response., We need to take on board the valuable and transferable lessons from the last outbreak   

    From CSIROscope: “Combatting Ebola through more than just outbreak response” 

    CSIRO bloc

    From CSIROscope

    9 August 2019
    Professor S.S. Vasan

    1
    An artificially coloured electron microscope image of the Ebola virus

    The World Health Organization has declared Ebola a ‘Public Health Emergency of International Concern’ (PHEIC), for the second time in five years. So, how can the global public health community better support relief efforts in the Democratic Republic of Congo (DRC)?

    Current situation with Ebola in the Democratic Republic of Congo

    The last major African outbreak mainly affected Sierra Leone, Liberia and Guinea, with 28,646 cases and a 40 per cent mortality rate. This epidemic killed five times more people than all other known Ebola outbreaks combined. And a PHEIC was declared between 8 March 2014 and 29 March 2016.

    After sporadic outbreaks in 2017 and 2018, the DRC is now experiencing the world’s second-largest recorded outbreak. As of 5 August 2019, 3150 people have infected with a 59 per cent mortality rate. Reports out of the region suggest that only half of the cases are being identified and reported. Most of them in the region of Kivu.

    The disease has also spread to neighbouring Uganda and been reported in places close to the DRC’s border with Rwanda and South Sudan.

    The decision to declare a PHEIC is a complex one. It involves weighing potential effects on travel and trade that could impede support to affected regions and hinder outbreak control, as argued by the World Health Organisation (WHO).

    What can developed countries do?

    The outbreak cannot be solved just with more funding and medical expertise that will arrive thanks to the PHEIC declaration.

    First and foremost, we need to listen to the local leadership and ask them what they need for a community-led response. And not assume what they want.

    The DRC Ministry of Health had asked for “more cohesion, more harmonization between the different interventions, [and] more alignment with the strategic plan of the Ministry of Health.” Lot of us want to help but are unsure how. So, we need more coordination to ensure each of us is focusing on our core competencies to address needs on the ground.

    Secondly, we need to take on board the valuable and transferable lessons from the last outbreak. This includes dialogue and delicate compromise with the community to ensure safe burial practices.

    Similar to the sustainable Resilient Zero program in Sierra Leone, we should strengthen their district health capacity, laboratory network and disease surveillance systems. We can then detect and respond effectively to not just Ebola, but also other infectious diseases.

    Thirdly, vaccination alone cannot solve Ebola. This is due to a range of factors including lack of 100 per cent protection, adverse effects, clinical and other challenges around coverage, compliance and cost-effectiveness. That is why the global scientific community needs to accelerate the development of treatments that complement the two experimental Ebola vaccines currently in use.

    Promising novel and repurposed drugs and treatments need to be evaluated in appropriate animal models in laboratories operating under the highest containment (‘Biosafety Level 4’). But such high secure facilities, like our own Australian Animal Health Laboratory (AAHL), are very few in number. So, we need greater coordination to ensure there is no duplication of efforts. Some mechanisms are already in place, such as the BSL4ZNet, an international network of laboratories like AAHL to protect against animal to human disease. And the fast track model agreement for rapid collaboration, which shares results for a global coordinated response.

    2
    A CSIRO infectious disease researcher working in the CSIRO high containment lab

    Looking long-term beyond outbreak response

    Recently there has been a greater risk of infectious diseases being transmitted to people from wild and domesticated animals. This is due to growth and geographic expansion of human populations and the increase in agricultural practices. Increased global travel also means there is a greater likelihood that infectious agents, particularly airborne pathogens that can produce disease, can rapidly spread among the human population. Together, these factors have increased the risk of pandemics. It’s not so much a matter of if, but when. While the current list of known emerging infectious diseases is a major concern, it’s the unknown viruses, with a potential for efficient human-to-human transmission that pose the biggest threat.

    Ebola and other haemorrhagic fever viruses are likely to re-emerge and pose a great threat to health and biosecurity. Especially in Africa and other developing nations. These settings have a relatively low health expenditure, high likelihood of such outbreaks, and an urgent need for rapid, safe, cheap and effective treatment options. Therefore, the typical 17 years’ ‘implementation gap’ in the health research translation process is simply not an option for Ebola and similar diseases.

    Ebola has increased the ‘intersectionality’ of suffering among the 13 million people living in a complex humanitarian crisis in the DRC. This includes ongoing conflict and widening health, wealth and gender inequalities. To solve this, we need a strong and locally-led social science and humanitarian focus. This would help guide scientific research, development, evaluation and uptake of response strategies and promising medical countermeasures. For the long-term, we need to focus on planning, preparedness and resilience, not just outbreak response.

    See the full article here .


    five-ways-keep-your-child-safe-school-shootings

    Please help promote STEM in your local schools.

    Stem Education Coalition

    SKA/ASKAP radio telescope at the Murchison Radio-astronomy Observatory (MRO) in Mid West region of Western Australia

    So what can we expect these new radio projects to discover? We have no idea, but history tells us that they are almost certain to deliver some major surprises.

    Making these new discoveries may not be so simple. Gone are the days when astronomers could just notice something odd as they browse their tables and graphs.

    Nowadays, astronomers are more likely to be distilling their answers from carefully-posed queries to databases containing petabytes of data. Human brains are just not up to the job of making unexpected discoveries in these circumstances, and instead we will need to develop “learning machines” to help us discover the unexpected.

    With the right tools and careful insight, who knows what we might find.

    CSIRO campus

    CSIRO, the Commonwealth Scientific and Industrial Research Organisation, is Australia’s national science agency and one of the largest and most diverse research agencies in the world.

     
  • richardmitnick 10:23 am on July 8, 2019 Permalink | Reply
    Tags: 7 Tesla MRI, , , , Medicine,   

    From Science News: “A 100-hour MRI scan captured the most detailed look yet at a whole human brain” 

    From Science News

    July 8, 2019
    Laura Sanders

    A device recently approved by the U.S. FDA made extremely precise images of a postmortem sample.

    1
    CLOSE-UP A 3-D view of the entire human brain, taken with a powerful 7 Tesla MRI and shown here from two angles, could reveal new details on structures in the mysterious organ.

    Over 100 hours of scanning has yielded a 3-D picture of the whole human brain that’s more detailed than ever before. The new view, enabled by a powerful MRI, has the resolution potentially to spot objects that are smaller than 0.1 millimeters wide.

    “We haven’t seen an entire brain like this,” says electrical engineer Priti Balchandani of the Icahn School of Medicine at Mount Sinai in New York City, who was not involved in the study. “It’s definitely unprecedented.”

    The scan shows brain structures such as the amygdala in vivid detail, a picture that might lead to a deeper understanding of how subtle changes in anatomy could relate to disorders such as post-traumatic stress disorder.

    To get this new look, researchers at Massachusetts General Hospital in Boston and elsewhere studied a brain from a 58-year-old woman who died of viral pneumonia. Her donated brain, presumed to be healthy, was preserved and stored for nearly three years.

    Before the scan began, researchers built a custom spheroid case of urethane that held the brain still and allowed interfering air bubbles to escape. Sturdily encased, the brain then went into a powerful MRI machine called a 7 Tesla, or 7T, and stayed there for almost five days of scanning.

    The strength of the 7T, the length of the scanning time and the fact that the brain was perfectly still led to the high-resolution images, which are described May 31 at bioRxiv.org. Associated videos of the brain, as well as the underlying dataset, are publicly available.


    ZOOM IN This video moves from the outer wrinkles to the inner structures and then back out to the wrinkles of a complete human brain at extremely high resolution.

    Researchers can’t get the same kind of resolution on brains of living people. For starters, people couldn’t tolerate a 100-hour scan. And even tiny movements, such as those that come from breathing and blood flow, would blur the images.

    But pushing the technology further in postmortem samples “gives us an idea of what’s possible,” Balchandani says. The U.S. Food and Drug Administration approved the first 7T scanner for clinical imaging in 2017, and large medical centers are increasingly using them to diagnose and study illnesses.

    These detailed brain images could hold clues for researchers trying to pinpoint hard-to-see brain abnormalities involved in disorders such as comas and psychiatric conditions such as depression. The images “have the potential to advance understanding of human brain anatomy in health and disease,” the authors write.

    See the full article here .


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    Please help promote STEM in your local schools.

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  • richardmitnick 2:08 pm on June 20, 2019 Permalink | Reply
    Tags: "Researchers Call for Personalized Approach to Aging Brain Health", , , Medicine,   

    From University of Arizona: “Researchers Call for Personalized Approach to Aging Brain Health” 

    U Arizona bloc

    From University of Arizona

    June 18, 2019
    Alexis Blue

    UA psychologist Lee Ryan and her collaborators have proposed a precision aging model designed to help researchers better understand and treat age-related cognitive decline on an individual level.

    People are living longer than ever before, but brain health isn’t keeping up. To tackle this critical problem, a team of researchers has proposed a new model for studying age-related cognitive decline – one that’s tailored to the individual.

    1

    There’s no such thing as a one-size-fits-all approach to aging brain health, says Lee Ryan, professor and head of the University of Arizona Department of Psychology. A number of studies have looked at individual risk factors that may contribute to cognitive decline with age, such as chronic stress and cardiovascular disease. However, those factors may affect different people in different ways depending on other variables, such as genetics and lifestyle, Ryan says.

    In a new paper published in the journal Frontiers in Aging Neuroscience, Ryan and her co-authors advocate for a more personalized approach, borrowing principles of precision medicine in an effort to better understand, prevent and treat age-related cognitive decline.

    “Aging is incredibly complex, and most of the research out there was focusing on one aspect of aging at a time,” Ryan said. “What we’re trying to do is take the basic concepts of precision medicine and apply them to understanding aging and the aging brain. Everybody is different and there are different trajectories. Everyone has different risk factors and different environmental contexts, and layered on top of that are individual differences in genetics. You have to really pull all of those things together to predict who is going to age which way. There’s not just one way of aging.”

    Although most older adults – around 85% – will not experience Alzheimer’s disease in their lifetimes, some level of cognitive decline is considered a normal part of aging. The majority of people in their 60s or older experience some cognitive impairment, Ryan said.

    This not only threatens older adults’ quality of life, it also has socioeconomic consequences, amounting to hundreds of billions of dollars in health care and caregiving costs, as well as lost productivity in the workplace, Ryan and her co-authors write.

    The researchers have a lofty goal: to make it possible to maintain brain health throughout the entire adult lifespan, which today in the U.S. is a little over 78 years old on average.

    In their paper, Ryan and her co-authors present a precision aging model meant to be a starting point to guide future research. It focuses primarily on three areas: broad risk categories; brain drivers; and genetic variants. An example of a risk category for age-related cognitive decline is cardiovascular health, which has been consistently linked to brain health. The broader risk category includes within it several individual risk factors, such as obesity, diabetes and hypertension.

    The model then considers brain drivers, or the biological mechanisms through which individual risk factors in a category actually impact the brain. This is an area where existing research is particularly limited, Ryan said.

    Finally, the model looks at genetic variants, which can either increase or decrease a person’s risk for age-related cognitive decline. Despite people’s best efforts to live a healthy lifestyle, genes do factor into the equation and can’t be ignored, Ryan said. For example, there are genes that protect against or make it more likely that a person will get diabetes, sometimes regardless of their dietary choices.

    While the precision aging model is a work in progress, Ryan and her collaborators believe that considering the combination of risk categories, brain drivers and genetic variants is key to better understanding age-related cognitive decline and how to best intervene in different patients.

    Ryan imagines a future in which you can go to your doctor’s office and have all of your health and lifestyle information put into an app that would then help health-care professionals guide you on an individualized path for maintaining brain health across your lifespan. We may not be there yet, but it’s important for research on age-related cognitive decline to continue, as advances in health and technology have the potential to extend the lifespan even further, she said.

    “Kids that are born in this decade probably have a 50% chance of living to 100,” Ryan said. “Our hope is that the research community collectively stops thinking about aging as a single process and recognizes that it is complex and not one-size-fits-all. To really move the research forward you need to take an individualized approach.”

    Ryan is associate director of the Evelyn F. McKnight Brain Institute at the UA, which is one of the foremost universities in the world for researching the aging brain and age-related cognitive changes. Her co-authors on the paper include UA Regents’ Professor of Psychology Carol Barnes, who directs the UA’s Evelyn F. McKnight Brain Institute; UA professors Meredith Hay and Matthias Mehl; and collaborators from the Phoenix-based Translational Genomics Institute, Georgia Institute of Technology, Leonard M. Miller School of Medicine and John Hopkins University.

    See the full article here .


    five-ways-keep-your-child-safe-school-shootings
    Please help promote STEM in your local schools.

    Stem Education Coalition

    U Arizona campus

    The University of Arizona (UA) is a place without limits-where teaching, research, service and innovation merge to improve lives in Arizona and beyond. We aren’t afraid to ask big questions, and find even better answers.

    In 1885, establishing Arizona’s first university in the middle of the Sonoran Desert was a bold move. But our founders were fearless, and we have never lost that spirit. To this day, we’re revolutionizing the fields of space sciences, optics, biosciences, medicine, arts and humanities, business, technology transfer and many others. Since it was founded, the UA has grown to cover more than 380 acres in central Tucson, a rich breeding ground for discovery.

    Where else in the world can you find an astronomical observatory mirror lab under a football stadium?

    U Arizona mirror lab


    An entire ecosystem under a glass dome? Visit our campus, just once, and you’ll quickly understand why the UA is a university unlike any other.

     
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