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School of Medicine leading multicenter study aimed at understanding brain development in babies with the condition

Kelly N. Botteron, MD, a professor of psychiatry and of radiology at Washington University School of Medicine in St. Louis, is leading a multicenter brain-imaging study focused on infants with Down syndrome. The five-year, $11.5 million grant from the National Institutes of Health (NIH) will focus on brain development in babies with the genetic syndrome.

Researchers at Washington University School of Medicine in St. Louis have received a five-year, $11.5 million grant to lead a multicenter effort to understand how brain development in babies with Down syndrome differs from that in other babies. The effort, which involves scanning the babies brains using MRI, will provide a foundation that may lead to therapies to counter developmental delays in children with the condition.

The grant, from the National Institutes of Health (NIH), is part of a $77 million initiative that began in 2018 to bolster basic and clinical research focused on infants and children with Down syndrome. Most people with the genetic condition have mild to severe developmental delays, learning disabilities, and distinct facial and physical features. Some also experience heart and gastrointestinal disorders.

Each year, about 6,000 babies in the U.S. are born with the condition.

It is astounding how sparse the research is involving neuroimaging characterization of neurodevelopment in Down syndrome, especially given that the condition is rather common, said the studys lead investigator, Kelly N. Botteron, MD, a Washington University professor of psychiatry and of radiology. Brain-imaging studies in children with Down syndrome are almost nonexistent. Before we can develop and assess therapies to improve cognitive outcomes, we need to understand more about the alterations in early brain development in these children.

Researchers will conduct behavioral and developmental testing, as well as MRI brain imaging, to examine the brain structure and cognitive function of 140 infants with Down syndrome and 70 babies without the condition. The children will be studied when they are 6 months old and, again, when they are 1 year old and then 2 years old.

The researchers also will compare the brain scans of the two groups of children with scans of autistic infants and toddlers. Such scans in autistic children have been part of a separate multicenter study co-led by Washington University.

This will give us a large set of data to detect differences in neurodevelopmental patterns, Botteron said. It will be eye-opening because there are some developmental characteristics that are unique to children with Down syndrome. They tend to have more motor and coordination delays, in addition to language delays. This information is critical to developing potential innovative treatment trials including additional physical therapy, applied behavior analyses, novel drugs and potential genetic editing techniques to improve both the quality of life and overall health of people with Down syndrome.

The infants will undergo MRI scans, generally in the evening after they fall asleep naturally, nixing the need for anesthesia. The researchers have developed strategies for scanning the brains of babies, based on MRI, without disturbing infants sleep.

Over the past 10 to 15 years, weve learned a lot about conducting brain imaging on infants and children with autism and healthy comparison controls, Botteron said.

One tactic is to introduce the babies beforehand to noise they can expect to hear from the MRI machine. Its important to prepare the babies and toddlers, she said. This means making them comfortable and scanning them at night while theyre naturally sleeping.

The studys other participants include researchers from the University of Washington in Seattle; Childrens Hospital of Philadelphia; University of North Carolina; University of Minnesota; New York University; and the Montreal Neurological Institute in Canada.

Washington University School of Medicines 1,500 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is a leader in medical research, teaching and patient care, ranking among the top 10 medical schools in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

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Brain imaging of babies with Down syndrome focus of $11.5 million grant - Washington University School of Medicine in St. Louis

Matthew Breen, a professor of genomics at NCState, says his 25-year career has roots in childhood heartbreak.

When I was young, my family had two dogs die from cancer and there was very little we could do to help them, says Breen. There were great strides being made with human cancer research, so why were we unable to help our animal companions more?

We are committed to making that change happen at NCState, he adds.

Today, the internationally recognized researcher specializes in molecular cytogenetics: the study of the structure and function of cells and chromosomes. His work in the College of Veterinary Medicine is helping our pets live longer, healthier lives and unlocking new insights about human cancers along the way.

Since joining NCStates faculty in 2002, Breen has focused on exploring the genetics and genomics of animal diseases, including how they initiate and respond to treatment.

He was a member of the team that sequenced the canine genome 14 years ago. The project sparked a new area of focus in his field: comparing the canine and human genomes to accelerate discoveries for both.

Humans and their furry friends actually share a very similar genetic makeup. And they share certain types of cancers, too. Many cancers diagnosed in humans and dogs have a similar pathology and clinical presentation, says Breen.

But when it comes to canines, its often easier to pinpoint the genetic abnormalities that lead to those cancers. This is especially the case for purebreds. Dogs of the same breed have less genetic variation among them than humans or mixed-breed dogs, making them an ideal genetic model.

Now, Breens lab works extensively in the area and hes become a pioneer in comparative oncology.

By working with human and animal cancers side by side, we are able to find shared features that may help identify the drivers of these cancers and provide opportunities to highlight targets for new therapies, says Breen.

Take, for example, Breens work with the BRAF gene.

Six years ago, his team discovered that a single mutation in the gene was found in 85% of dogs with transitional cell carcinoma (TCC) also called urothelial carcinoma (UC) which is the most common form of bladder cancer in canines. More than 80,000 dogs in the United States will be affected this year alone.

This particular BRAF mutation was already known to exist in some human cancers, but Breens discovery helped unlock its significance for both species. It also revealed an opportunity to create a much-needed tool to aid diagnosis.

By working with human and animal cancers side by side, we are able to find shared features.

In most cases, canine bladder cancer isnt diagnosed until it has reached an advanced stage. Thats because the cancer shares many clinical signs with other, more common urinary tract conditions.

Treatments for the common alternatives may alleviate symptoms temporarily, but they mask the larger problem and buy the cancer more time to progress. In fact, upon diagnosis, more than half of canine bladder cancer cases have already spread.

Identifying the BRAF mutation as a genetic signature of canine bladder cancer was a powerful insight. From there, Breens team began developing a molecular diagnostics test that could identify the mutation and detect the cancer earlier than ever.

That molecular test called CADET BRAF was developed in Breens research laboratory in 2014. Using a urine sample, the system detects cells that possess the BRAF mutation and can monitor changes in the number of mutated cells being shed during treatment of canine TCC and UC.

CADET BRAF represents the worlds first liquid biopsy for the detection of cancer in veterinary medicine, says Breen.

It offers several improvements over current alternatives. Requiring only a simple free-catch urine sample, CADET BRAF is the only non-invasive approach. Other methods often involve costly procedures, such as sedation or anesthesia, that carry additional risks.

The test can also detect bladder cancer in the early stages of the disease, potentially leading to improved outcomes.

CADET BRAF represents the worlds first liquid biopsy for the detection of cancer in veterinary medicine.

We can detect the cancer in dogs that have already presented with clinical signs and avoid repeated attempts to treat solely the signs, says Breen. That allows more time for the veterinarian and owner to develop a plan to treat the root cause. In addition, we have been able to detect the presence of very early disease, several months before the dog has any clinical signs.

Now we have to determine how to manage these preclinical patients, and that is part of ongoing work by our team at NCStates College of Veterinary Medicine, he adds.

The test is also dependable. After rigorous validation of thousands of dogs, Breen says hes found that the presence of the BRAF mutation in canine urine is a highly reliable indicator of the presence of TCC/UC. Weve shown the BRAF mutation isnt found in the urine of healthy dogs or dogs that have other common conditions such as bladder polyps, inflammation or chronic cystitis, he says.

In the two years following the development of CADET BRAF, Breen focused on developing a strong proof of concept. Teaming up with the American Kennel Club, he recruited urine samples from hundreds of dogs to show that the approach could work with real patients.

His next step was commercialization. Breens startup, Sentinel Biomedical, was formed in 2015. Located right on NCStates campus, the company works to develop and scale diagnostic tests for the health care industry.

Since its formation, theyve developed another product called CADET BRAF-PLUS. The test is designed for dogs who dont have the BRAF mutation but do show clinical signs of TCC/UC. It can detect over two-thirds of bladder cancer cases not identified by CADET BRAF, increasing the overall detection sensitivity of the tests to over 95%.

Headquartered right on NCStates campus, Sentinel Biomedical seeks to improve diagnosis and treatment for dogs and their owners.

Find out more

Whats next for Sentinel Biomedical? It recently announced a joint venture with Antech Diagnostics, part of MARS. Together theyve formed Antech Molecular Innovations, also based on NCStates Centennial Campus, and work to broaden access to CADET BRAF and CADET BRAF-PLUS.

With the distribution channels of one of the worlds largest animal health providers, we are providing veterinarians with easy access to the tests we develop and enhancing our ability to become a global leader in innovation for veterinary molecular diagnostics, says Breen. And because our work is translational, we also have greater potential to translate our findings to humans.

This will bring the innovations developed at NCState to a whole new level.

Today, the National Cancer Institute spends $6 billion on cancer research annually, and its estimated that less than 0.5% is directed toward veterinary oncology. But Breen sees his innovations and those of his colleagues across the nation as promising steps in the right direction.

Currently, hes involved in a clinical study in the College of Veterinary Medicine that will evaluate the timeline between when a BRAF mutation is detected in a dogs urine and when that dog begins to show clinical signs of TCC/UC. Breen hopes this knowledge will lead to earlier intervention, improved quality of life and increased survival rates.

This will bring the innovations developed at NCState to a whole new level.

Recent collaborations with colleagues at Duke Cancer Institute are also exploring the genetic and environmental factors shared between canine and human bladder cancers. A study proposed by this multidisciplinary team was awarded funding from the V Foundation for Cancer Research in 2019. Such comparative oncology studies, Breen says, have the potential to realize the true value that dogs can bring to our fight against cancer.

Through Antech Molecular Innovations, Sentinel Biomedical has begun pursuing more projects to provide rapid, accessible molecular diagnostics for a variety of cancers that impact our pets and ourselves.

For now, Breen is excited to see his work take on a wider reach. These cancer detection tests will help a new generation of canine companions and their human friends (maybe even kids who are experiencing what Breen did as a child). Whats more, the increased volumes of data theyll collect may unlock insights that lead to the development of new treatment opportunities for cancers in both species.

Although we may not be able to help all dogs with cancer today, we are driven to learn from their cancers to help the dogs of tomorrow, and the families who care for them, says Breen.

Excerpt from:
Sniffing Out Cancer in Canines And Humans, Too - NC State News

Delirium is the most common post-surgical complication in older adults. Marked by acute temporary confusion, disorientation and/or agitation, it strikes as many as half of adults over 65 who undergo high-risk procedures such as cardiac surgery and hip replacements.

Postoperative delirium is also tightly linked to Alzheimers disease. Although each can occur independently, Alzheimers is a leading risk factor for delirium, and an episode of delirium puts patients at increased risk for cognitive decline and Alzheimers.

However, the physiological mechanisms that link delirium and Alzheimers disease remain largely unknown.

Get more HMS news here

Now, in a paper published Nov. 22 in Alzheimers & Dementia: The Journal of the Alzheimers Association, researchers at Harvard Medical School and Beth Israel Deaconess Medical Center shed light on a genetic risk factor for Alzheimers disease that may indirectly influence patients risk of postoperative delirium.

In a study of older adults without dementia undergoing major noncardiac surgery, researchers observed that patients carrying a specific variant of a gene appeared to be much more vulnerable to delirium under certain conditions than people without the variant.

The teams findings could open the door to future interventions to prevent or mitigate postoperative delirium in at-risk patients.

Our findings confirmed our hypothesis that patients risk of postoperative delirium differs by genetic predisposition, said Sarinnapha Vasunilashorn, assistant professor of medicine at HMS and Beth Israel Deaconess and first author of the study. We observed a strong and significant association between high postoperative inflammation and delirium incidence, duration and severity among patients carrying a variant of the gene considered to be risky, while the association was weaker and nonsignificant among noncarriers.

Vasunilashorn and colleagues focused on a gene called APOE, short for apolipoprotein E. The risky version of the gene, notated as APOE 4, is the strongest known genetic risk factor for late-onset Alzheimers disease and a widely studied genetic risk marker for delirium.

While recent studies have shown no direct relationship between APOE 4 and delirium, Vasunilashorns team hypothesized that the gene variant might indirectly influence risk of delirium by modifying the bodys response to inflammationpart of the immune systems natural defense systemindicated by the presence of an inflammatory marker in the blood called C-reactive protein, or CRP.

Using data from the Successful Aging after Elective Surgery (SAGES) study, an ongoing prospective cohort study investigating risk factors and long-term outcomes of delirium, the scientists looked at the incidence, severity and duration of delirium in 560 patients who were at least 70 years old and who underwent major noncardiac surgeries under general or spinal anesthesia. Patients were monitored for delirium, assessed by daily cognitive assessments of attention, memory and orientation throughout their hospital stay.

Analyzing data from patients blood drawn before surgery, immediately after surgery, two days after and one month after revealed that, among carriers of the APOE 4 gene variant, patients with high levels of inflammation had an increased risk of postoperative delirium. However, among noncarriers of the APOE 4 gene variant, the scientists found no such association.

Our findings suggest that APOE 4 may be an indicator of brain vulnerability, said Vasunilashorn. This work may inform the targeting of future interventions, such as anti-inflammatory treatments, for prevention of postoperative delirium and its associated adverse long-term cognitive outcomes in patients with this genetic susceptibility.

Edward Marcantonio, professor of medicine at HMS and Beth Israel Deaconess, is senior author of the study.

This work was supported by the National Institute of Aging of the National Institutes of Health (grants K01AG057836, R03AG061582, P01AG031720, R24AG054259, K07AG041835, R21AG057955, R01AG041274, R21AG048600, R01AG051658 and K24AG035075); the Charles A. King Trust Postdoctoral Research Fellowship Program; Bank of America, N.A., Co-Trustee, and the Alzheimers Association (AARF-18-560786).

Adapted from a Beth Israel Deaconess news release.

Image: kemalbas/Getty Images

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Gene linked to Alzheimers disease plays indirect role in risk for... - ScienceBlog.com

Dr Sadaf Farooqi

BRIGHTON, UK The obesity epidemic is not simply the result of changes in the lived environment but a complex interplay between genes and surroundings that has driven people who would have been genetically susceptible but remained thin in previous eras to become obese, says one expert.

This was the argument put forward as part of a debate on whether an individual's body weight is determined by "nature or nurture" at the recent Society for Endocrinology BES Conference 2019 in Brighton, UK.

Before the debate began, Rob Semple, MD, University of Edinburgh, UK, introduced the speakers and polled the audience on their "baseline" views onthe statement: "This house believes that nature not nurture determines our body weight."

The response was 36% "for" the statement (ie, nature) and 64% "against,"which Semple noted suggested that the first speaker, Sadaf Farooqi, MBChB, PhD, "will have her work cut out" to convince the audience that nature is the main driver of obesity.

Farooqui is professor of metabolism and medicine at the University of Cambridge, UK, and was the winner of the 2019 American Diabetes Association Outstanding Scientific Achievement Award.

Farooqi's adversary in the debate was John Wilding, DM, of the University of Liverpool, UK, who Semple described as "similarly formidable."

Farooqi began by saying that the question before the audience is "fundamentally important," and noted that there is plenty of evidence to suggest there is a biological system for regulating body weight.

Experiments have shown that animals and humans maintain a set point for weight that they return to after periods of limited food intake, regardless of how much weight they lose.

Initially, the hypothalamus was found to play a key role in weight regulation, but it was the discovery of leptin that allowed the whole system, with its links to adipose tissue, the pancreas, and the intestines, to be elucidated, she explained.

Work with children then revealed the influence of genetic factors on the body weight "set point."

Identical twins reared apart were found to have a very similar body weight, and adoptive children were shown to have a similar weight to their biologic, rather than adoptive, parents.

Tying these observations to individual or small numbers of genetic variants has, however, proven difficult, beyond the known variants associated with thinness and the rare variants in 15 genes linked to severe obesity.

That is, Farooqi said, until the publication of US research earlier this year testing a polygenic risk predictor involving 2.1 million common variants in more than 300,000 individuals.

The research showed that, across polygenic score deciles, there was a 13-kg gradient in weight and a 25-fold gradient in the risk of severe obesity.

Moreover, another 2019 study, this time by Farooqi's team, revealed some loss of function variants in the melanocortin 4 receptor gene are linked to an increased risk of obesity, type 2 diabetes, and coronary artery disease, and some gain in function variants are linked to a lower risk of obesity and cardiometabolic disorders.

Farooqi believes the reason there is an obesity epidemic is that the physiological system for regulating weight "evolved to stop us starving" but is now faced with "an abundance of food."

The impact of this is all the greater because we live in a "complex food environment," with high sugar and high fat foods that are seen as "very rewarding," as demonstrated on brain scans of people shown pictures of such foods.

Individuals also engage in stress-related eating, which is played out via neural circuits linking the hypothalamus to the limbic system.

She characterized such eating as a "biologically appropriate thing to do because it gives you a rewarding, pleasurable feeling."

She said that, together, this underlines that the "biology of appetite" is a mixture of both innate and learned behaviors.

Farooqi concluded: "I hope I've made the case for you that there is clear, strong, compelling evidence" that weight is regulated by a homeostatic system centered on the hypothalamus, and genetic disorders, tumors, surgery, radiotherapy, and medications can all "perturb" weight regulation.

"In some people, that promotes obesity, in some people it protects them against obesity," she said.

Dr John Wilding

Taking to the podium, Wilding proceeded to present the case for the notion that body weight is determined "by nurture."

He pointed to data from the World Obesity Federation on adult obesity showing that, between the 1960s and 1990s, the prevalence of obesity topped more than 15% in only a few developed countries and no developing nations.

But from 2000 onwards, the situation has completely reversed. At least 15% of the population is obese in most developed countries, rising to over 25% in the United States, Canada, Australia, and the UK, among others. The prevalence of obesity is also rising rapidly in many middle-income countries.

Yet, Wilding pointed out, humanity cannot have evolved genetically to a sufficient extent over that period to account for the change.

He turned to the UK Government's obesity system map, which is a visual representation of the different factors that influence obesity levels.

Although it places physiological energy balance at the heart of the map, and a large part of that is devoted to biologic processes, Wilding highlighted that the visual also places a great degree of emphasis on food production and consumption, societal influences, individual psychology and movement, and the "activity environment."

He also showed data suggesting it is not so much energy and fat intake that is associated with obesity trends as the increase in the number of cars per household and hours spent watching television.

For example, it is estimated that, compared with the 1950s, the average adult now walks, on average, a marathon (approximately 26 miles) less per week, he said.

The Cuban economic crisis of the 1990s also provides an illuminating example, Wilding added.

The sudden end of Soviet subsidies to Cuba led to food shortages, the loss of public and private transport, and the importof 1.5 million bicycles from China.

The subsequent drop in the prevalence of obesity was associated with a reduction in the incidence of diabetes and diabetes-related mortality, with all three increasing substantially once food and transport levels were restored.

Taking a more recent example, Wilding showed longitudinal findings from the HUNT study, which involved almost 119,000 individuals with repeated body mass index (BMI) measurements from 1963, and over 67,000 who were tested for 96 known obesity genes.

The HUNT authors concluded that, although "genetically predisposed people are at greater risk for higher BMI and that genetic predisposition interacts with the obesogenic environment resulting in higher BMI...BMI has increased for both genetically predisposed and nonpredisposed people, implying that the environment remains the main contributor."

Wilding said that, taken together, obesity is "common and increasing almost everywhere," and that the epidemic "is driven by societal change," despite the underlying biology determining an individual's susceptibility.

He ended his pitch to much laughter with a quote by Farooqi from a 2014 review that supports his argument: "Evidence clearly shows that both increases in energy intake and reductions in energy expenditure during physical activity have driven increases in the mean BMI seen in many countries over the past 30years."

Both speakers were then invited back to the podium, allowing Farooqi to respond that, although she did indeed pen that statement in a 2014 review, if one were to look "carefully," the article discussed the last 30 years, and indeed, "our genes haven't changed in that time, but the environment has."

"We agree on that point, and hence my quote," she said, "but what our environment has done is it has unmasked the genetic susceptibility of some individuals, so what we see when we look at the pattern of BMI in the population is that the mean BMI has increased...but also the proportion of people with severe obesity has increased."

She clarified that what this suggests is that, within any population, there are some people who are genetically more susceptible to obesity, so some of those who may not have been obese 30 years ago now are because of the environment.

"It is the environment acting on genetic susceptibility that is contributing to the distribution of BMI," she emphasized.

Wilding again pointed to the HUNT study, which showed that, even in individuals with "thin genes," there has been a rise in mean BMI.

Farooqi said this, in fact, underlines a limitation of that study, which is they only used 96 well-known genetic variants associated with obesity, but the polygenic risk study she highlighted earlier used 2.1 million genetic variants.

Consequently, data from the HUNT study "captures some of the variation but not all," she stressed.

The debate continued, with questions from the floor covering many aspects of obesity.

The final question was directed at Farooqi: "What proportion of somebody's weight is considered to be genetic...as opposed to the nurtured weight?"

She replied this is a "hugely important" question, because "if we don't recognize that theres a biological role for the regulation of weight, how on earth can politicians, with their somewhat different capacity for taking on new information, do that?"

The "evidence suggests around 40% of a person's weight is influenced by genetic factors," she said.

"In some people it's higher, where there are penetrant genes having an effect, in other people it's about 40% with a combination of genes which, added together, influence their risk of either gaining weight or staying thin."

In response, Wilding was keen to stress: "No matter which side of the argument you're on, the point is that this is not the individual's fault."

"It's either a response to their environment...or it's something that they've inherited and don't have individual control over," he noted.

"Sadaf [Farooqi] said it herself, 40% of our body weight is genetic, that means that 60% is environmental, and I rest my case," Wilding said.

However, that did not hold sway with the audience, who, when they voted again at the end of the debate, indicated they had changed their minds: 53% agreed with the statement that nature, not nurture, determines body weight, and 47% disagreed.

A win for the lady, it would seem.

Society for Endocrinology BES 2019. Presented November 11, 2019.

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Nature vs Nurture: What's Fueling the Obesity Epidemic? - Medscape

Posted By: Staff WriterNovember 18, 2019

With artificial intelligence and genetic engineeringcontinuing to shape the future of scientific innovation and discovery,questions about the ethical implications only seem to get more complicated.

Additionally, CRISPR a tool for DNA sequencing and geneediting is bringing new technological changes and advancements in a rapidlyshifting landscape.

A panel discussion at Stanford University later thisweek, moderated by Russ Altman a professor of Bioengineering, Genetics,Medicine, Biomedical Data Science and Computer Science at the university, seeksto discuss how AI and CRISPR are influencing these ethical quandaries and howthey might influence the evolutionary process.

The two panelists for the free, sold-out event areleaders in the field. Jennifer Doudna, a professor of chemistry and molecularand cell biology at UC Berkeley, helped discover CRISPR-Cas9. Fei-Fei Li is acomputer science professor at Stanford in the universitys Institute forHuman-Centered Artificial Intelligence. She previously worked at the schoolsAI Lab and at Google.

The Institute for Human-Centered Artificial Intelligenceis hosting for forum at Stanfords CEMEX Auditorium, 655 Knight Way. It is setfor Tuesday, November 19, from 7 to 8:30 p.m.

While the event has sold out of pre-registration tickets,limited general admission will be available at the site. It will also belivestreamed.

To see more details, click here.

To watch the livestream, click here.

Originally posted here:
Examining the ethics of scientific discovery - Cupertino Today

Mila Makovec has high pigtails in her dark hair and a cloth doll tucked under her arm as she wakes up in a hospital bed, where shes just been injected with a one-of-a-kind drug intended to save her life.

The drug works for only one person in the world this 9-year-old girl from Boulder.

In a spectacular example of what the future might hold for precision medicine, the drug was made only for her in a quest to save Mila from a neurological disease that is destroying her brain. Her DNA is in the formula. The 22-letter genome sequence in the drugs recipe matches the one in Milas cells that is broken.

It is the first time the FDA has approved a drug for a single person.

The drug appropriately called milasen might not have come soon enough to save Mila, as it can only slow the process of degeneration, not replace the brain cells that have already died.

But this story is no longer just about Mila; it never actually was.

This is not just for my daughter anymore, said Julia Vitarello, who took to social media to fundraise and find a researcher and drug manufacturer who would help her. This is for something much bigger.

Milas case catapulted specialized drug development at least a decade into the future, her doctors say, opening a new path for other children with rare genetic diseases that have no cure.

Childrens Hospital Colorado, where Mila was diagnosed three years ago and now receives her treatment, and Boston Childrens, where her drug was designed, are leading the way in creating a model in which academic researchers could help perhaps a handful of children each year by crafting one-of-a-kind medicines. Next year, Childrens Colorado will begin whole-genome sequencing with a new machine called a Novaseq, a major step in the process of finding mutations in DNA.

The whole concept raises ethical questions for sure: How safe is it to initiate a clinical trial for a single child? Who makes sure the children who could benefit most not just those whose families have money or the ability to raise money get the specialized treatment?

Vitarello, who created Milas Miracle Foundation and raised $3 million while trying to save her daughter, wants to establish funding for children who need drugs tailored to their own cellular biology. She suggests an admissions process where the researchers deciding whether to help a child do not know that childs name, face or ability to pay.

There are going to be parents who are going to do anything for their kid, Vitarello said. They are going to come with money. Thats totally fine, no judgment. I would do the same thing. But in an ideal world, there would be patients coming through a funnel with no names or faces or money attached. Whoever is at the table makes the best decision.

The path forward is likely in the academic, nonprofit space, Vitraello said. She is initiating talks with the National Institutes of Health, the largest public funder of biomedical research, as well as research institutions, the FDA and the pharmaceutical industry. An estimated 1.3 million people with rare genetic diseases could potentially benefit from a treatment like Milas, she said.

There are 1.3 million kids that are dying that have no other treatment, no pharma company is going to help them, there is nothing that we can do, and now suddenly, weve opened up a pathway for that, she said Tuesday at the hospital in Aurora, as Mila rested following her injection. The only way to get it is to have more academic institutions treat more kids one, two, five, 10. Open it up.

The goal is that kids with flaws in their DNA could receive precision medicine sooner, halting neurological diseases before they steal the ability to walk, talk, eat or see.

Mila was a perfectly healthy child the first three years of her life. She was learning to ski, went hiking with her parents and had a vocabulary advanced beyond her years.

Her mom noticed the subtle changes before anyone the way she pulled books close to her face because she couldnt see, how her feet turned inward, that she began bumping into things and fell for no reason, how she stuttered sometimes but it wasnt like typical stuttering.

Vitarello brought her to 100 doctors and therapists from the East Coast to the West and in Canada, many of whom told her to calm down and that her daughter seemed fine. I had doctors tell me I was pretty much crazy. Very top level doctors told me to chill out, she said. Well, I wasnt going to chill out. I just kept going.

By age 7, Mila was having trouble walking and eating and was going blind. Her body was wracked with multiple seizures each day.

I spent three years trying to figure out what was wrong with her, Vitarello said. I basically gave up and brought her to the ER at Childrens Colorado.

Mila was admitted and her case assigned to Dr. Austin Larson, a geneticist whose main job at the hospital is to figure out whats wrong with patients who have an undiagnosed disease. An MRI found that the part of Milas brain that is responsible for balance, the cerebellum, was smaller than expected. But it was a genetic test that for the first time gave Vitarello a name for Milas illness: Batten disease, and a specific type of Batten that is so rare, just 25 people in the world are known to have it.

The disease occurs when both of a childs two CNL7 genes are mutated one mutation from each parent.

Larson was able to identify the defective gene from Milas father, but could not find one from her mother. At the time, Childrens Colorado along with most places didnt have the technology to search that deeply into Milas DNA through whole-genome sequencing, and Larson warned Milas family that it was likely impossible to find a clinical lab that could. She would need a researcher.

Vitarello turned to Facebook, begging for help for Mila but also so she could find out if her son, who was 2 at the time and completely healthy, had the same devastating disease that was taking away her daughter.

I was going to get nowhere with Mila unless I just opened up my story fully, to everyone, her mom said.

Dr. Larson had given her enough information and the right words to make a plea. A Boston physician saw her message and connected her with Dr. Timothy Yu, a neurogeneticist at Boston Childrens.

At the same time, the FDA had just approved a new drug called Spinraza, the first drug to treat a separate genetic condition called spinal muscular atrophy. The drug, injected into the fluid around the spinal cord, helped babies in clinical trials improve head control, sitting and standing.

The way Spinraza was designed was a game-changer for medicine and key in helping Mila. Yu and his team in Boston wondered if they could make a similar drug for the Colorado girl.

The Boston team spent days staring at screens of Milas DNA sequences until they discovered the other piece of the genetic puzzle in addition to the gene mutation from her father, Mila had inherited extra genetic material from her mother. The combination meant that, in the most basic terms, Mila had a sequence of broken DNA in her cells.

The drug created only for Mila contains little pieces of synthetic genetic material that search for a specific 22-letter sequence and cover it up so that her cells cannot read it. We are taking a Band-Aid and sticking it onto that part, said Dr. Scott Demarest, a pediatric neurologist at Childrens Colorado and a specialist in rare genetic epilepsies. That is literally what is happening. It is sticking to that spot so that the cell skips over that and goes to the next part that is correct.

The only difference between Spinraza and milasen is the genetic sequence inside the drugs send Band-Aids to different addresses.

After discovering the genetic flaw, Yu in Boston and Larson in Colorado called Milas mom together to give her the news. Her son did not have either of the recessive genes, and her daughter had both.

It was a huge mix of extreme happiness and, within the same second, just extreme falling-to-the-floor sadness for Mila, Vitarello recalled. My daughter had gotten both of the bad mutations and my son had gotten both of the good ones.

Next, Vitarello had to persuade a drugmaker to make a drug for one, and the FDA to allow doctors to inject it in her daughters spinal fluid.

The stars aligned, she says, still in disbelief.

Milas team made it happen by emphasizing that although this drug had the potential to work only on one person, the process could become a blueprint for other patients. Only the DNA sequence in the medicine would change.

They persuaded a drug manufacturer in California, TriLink Biotechnologies, to make Milas drug. And the FDA agreed to speed up the clinical trial process by allowing Yu to test the drug on rats at the same time Mila was receiving her first dose. The doctor had first tested it on Milas skin cells.

Milasen is technically now in clinical trial a trial of one patient involving two childrens hospitals.

The night before Milas first injection in January 2018, as Vitarello went for a run in subzero Boston, she told herself she was OK with whatever happened. Mila was out of time. Vitarello had seen the descriptions online and knew where Mila was headed.

My daughters trajectory of not treating her was so black and white, Vitarello said. Everyone always wonders what is going to happen to your life. When you have a rare disease, you can see exactly what is going to happen to your child ahead of time and its not a good thing.

I figured the worst-case scenario was not her dying, it was her being in pain, Vitarello said, recalling that she asked Yu to tell the FDA that she thought the drugs potential benefits outweighed the risk. I said, If my daughter dies on the spot, Im OK with that.

Instead, the injections that first year seemed to stop the diseases progression. Mila quit eating through a g-tube and started eating her moms pureed food again. She could hold up her head and her upper body, and her walking improved. Her seizures decreased from 30 a day to two or three.

Quality of life, those are huge, Vitarello said.

Now in the second year of treatment, some of Milas symptoms have declined, but not as steeply as other children with her disease. Milas team has upped her doses and started injecting them every two months instead of every three, but they have no precedent to follow.

They could find out years from now that they were giving Mila 1,000 times too little, her mother said.

I honestly dont know if it was in time for Mila, Vitarello said. She was really progressed when she received her treatment. There is still hope.

The key to saving more children from rare genetic diseases is diagnosing them earlier ideally at birth.

What if we found this three years sooner? Larson asked. I think about that a lot. What would it have taken to have found this the first time that (Vitarello) took Mila to a physician and said, I am concerned about the subtle difference in the way she walks?

The answer is it takes having a very broad test and being very good at interpreting that very broad swath of information.

Science is a ways off from being able to detect diseases as rare as Milas in newborns. But breakthroughs are coming for other genetic diseases.

Starting in January, spinal muscular atrophy will become one of 38 genetic diseases newborn babies are screened for via blood tests, said Raphe Schwartz, chief strategy officer for Childrens.

Childrens intends to take what it has learned through Milas case, partner with other institutions and use it to help more children, Schwartz said. What we learn reveals the roadmap for the future, he said. The future ones we do are more effective and less expensive over time.

There is a sense of urgency, but also caution.

We want to make sure we are doing it right, we are doing it safely, we are doing it for kids who are going to benefit the most, Demarest said. There are ethical challenges around it. We need to be very thoughtful and careful that we are doing this the right way, but were also doing it in a way that allows this to be a reality for kids as soon as possible and for as many as possible.

For now, Vitarello is grateful that Mila can receive her treatments in Colorado. Until September, they were traveling to Boston every other month for 10 days, but now they can leave home after breakfast on treatment days and return by dinner.

On Tuesday, Vitarello recited Goldilocks and the Three Bears and sang camp songs while Mila, bundled in blankets, received the 10-minute injection in her lower back, which Vitarello said doesnt seem to hurt Mila. They celebrated Milas 9th birthday last week, and her little brother, now 5, picked out a squishy toy and a sequined mermaid for her birthday presents.

Im faced with a huge amount of sadness around this, but at the same time, its making such a huge difference that it gives a lot of purpose to her life and it gives a lot of purpose to my life, Vitarello said. We are still fighting hard for Mila. But I can see this making a much bigger impact.

This reporting is made possible by our members. You can directly support independent watchdog journalism in Colorado for as little as $5 a month. Start here: coloradosun.com/join

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This miracle drug was designed and manufactured for just one person a 9-year-old Boulder girl - The Colorado Sun

News Release

Wednesday, November 20, 2019

Studies in cell and animal models reveal insights into cancer cells vulnerability that could lead to new strategies against brain cancers.

Researchers have devised a new plan of attack against a group of deadly childhood brain cancers collectively called diffuse midline gliomas (DMG), including diffuse intrinsic pontine glioma (DIPG), thalamic glioma and spinal cord glioma. Scientists at the National Institutes of Health, Stanford University, California, and Dana-Farber Cancer Institute, Boston, identified a drug pair that worked together to both kill cancer cells and counter the effects of a genetic mutation that causes the diseases.

The researchers showed that combining the two drugs panobinostat and marizomib was more effective than either drug by itself in killing DMG patient cells grown in the laboratory and in animal models. Their studies also uncovered a previously unrecognized vulnerability in the cancer cells that scientists may be able to exploit to develop new strategies against the cancer and related diseases. The results were published Nov. 20 in Science Translational Medicine.

DMGs are aggressive, hard-to-treat tumors that represent the leading cause of brain cancer-related death among U.S. children. DMGs typically affect a few hundred children a year between ages 4 to 12; most children die within a year of diagnosis. Most cases of DMG are caused by a specific mutation in histone genes. Histones are protein complexes in the cell nucleus. DNA wraps around histones to form chromatin, which packages DNA in the nucleus. How DNA winds and unwinds around histones is influenced by enzymes, including histone deacetylases. These enzymes add or remove chemical tags, which indirectly controls if genes are turned on or off.

In an earlier study, Stanford neuro-oncologist Michelle Monje. M.D., Ph.D., and her colleagues showed that panobinostat, which blocks key histone deacetylase enzymes, could restore the DIPG histone function to a more normal state. While panobinostat is already in early clinical testing in DIPG patients, its usefulness may be limited because cancer cells can learn to evade its effects. So Monjes team wanted to identify other possible drugs and combinations of them that could affect the cancer.

Very few cancers can be treated by a single drug, said Monje, a senior author of the study who treats children with DIPG and other diffuse midline gliomas. Weve known for a long time that we would need more than one treatment option for DIPG. The challenge is prioritizing the right ones when there are thousands of potential options. Were hopeful that this combination will help these children.

Monje and the National Cancer Institutes Katherine Warren, M.D., now at Dana-Farber Cancer Institute and Boston Childrens Hospital, collaborated with Craig Thomas, Ph.D., and his colleagues at the NIHs National Center for Advancing Translational Sciences (NCATS). Thomas and his team used NCATS drug screening expertise and matrix screening technology to examine drugs and drug combinations to see which ones were toxic to DIPG patient cells.

NCATS robotics-enabled, high-throughput screening technologies enable scientists to rapidly test thousands of different drugs and drug combinations in a variety of ways. Scientists can examine the most promising single drugs and combinations, determine the most effective doses of each drug and learn more about the possible mechanisms by which these drugs act.

The NCATS researchers first studied the effects of single approved drugs and investigative compounds on DIPG cell models grown in the laboratory from patient cells. They focused on agents that could both kill DIPG cells and cross the brains protective blood-brain barrier, a necessity for a drug to be effective against DIPG in patients. The team then tested the most effective single agents in various combinations.

Such large, complex drug screens take a tremendous collaborative effort, said Thomas, also a senior study author. NCATS was designed to bring together biologists, chemists, engineers and data scientists in a way that enables these technically challenging studies.

While there were multiple, promising outcomes from these screens, the team focused on the combination of histone deacetylase inhibitors (like panobinostat) with drugs called proteasome inhibitors (such as marizomib). Proteasome inhibitors block cells normal protein recycling processes. The panobinostat-marizomib combination was highly toxic to DIPG cells in several models, including DIPG tumor cell cultures that represented the main genetic subtypes of the disease and mice with cells transplanted from patient tumors. The combination also reduced tumor size in mice and increased their survival. A similar response was found in spinal cord and thalamic DMG models developed from cells grown in culture from patient cells.

The screening studies also provided important clues to the ways the drugs were working. Building on these data, the collaborative team subsequently conducted a series of experiments that showed the DIPG cells responded to these drugs by turning off a biochemical process in the cells mitochondria that is partly responsible for creating ATP, which provides energy to cells. The drug combination essentially shuts down tumor cell ATP production.

The panobinostat-marizomib drug combination exposed an unknown metabolic vulnerability in DIPG cells, said first author Grant Lin, Ph.D., at Stanford University School of Medicine. We didnt expect to find this, and it represents an exciting new avenue to explore in the development of future treatment strategies for diffuse midline gliomas.

Plans are underway for clinical trials of the drug combination and of marizomib alone.

Many drugs that we test have multiple effects on DIPG cells, said Warren, a senior study author. Panobinostat, for example, inhibits a specific enzyme, but it has other mechanisms working in tumor cells that may contribute to its effectiveness. Were still trying to understand the various Achilles heels in these cancer cells. This work is an important step in translating our preclinical data into patients.

Monje stressed the panobinostat-marizomib combination might be an important component of a multitherapy strategy, including approaches that harness the immune system and those that disrupt factors in the tumor microenvironment that the glioma cells depend on to grow. Like Warren, Monje emphasized the need to better understand how drugs target and impact the DIPG cells vulnerabilities.

Our work with NCATS showed the need to gather more preclinical data in a systematic, high-throughput way to understand and prioritize the strategies and agents to combine, Monje said. Otherwise were testing things one or two drugs at a time and designing clinical trials without preclinical data based on hypothesized mechanisms of action. We want to move past this guesswork and provide preclinical evidence to guide clinical decisions and research directions.

Lin added, The idea is to get as many effective tools as possible to work with that can have an impact on patients.

The research was funded by Alexs Lemonade Stand Foundation, Izzys Infantry Foundation, McKenna Claire Foundation, Unravel Pediatric Cancer, Defeat DIPG Foundation, ChadTough Foundation, N8 Foundation, Kortney Rose Foundation, Cure Starts Now Foundation and the DIPG Collaborative, Sam Jeffers Foundation, Lyla Nsouli Foundation, Abbies Army Foundation, Waxman Family Research Fund, Virginia and D.K. Ludwig Fund for Cancer Research, National Institute for Neurological Disorders and Stroke (R01NS092597) and NIH Directors Common Fund (DP1NS111132), Maternal and Child Health Research Institute at Stanford, the Anne T. and Robert M. Bass Endowed Faculty Scholarship in Pediatric Cancer and Blood Diseases, The DIPG All-In Initiative and the NCATS and NCI intramural programs.

Reference:GL Lin et al. Therapeutic Strategies for Diffuse Midline Glioma from High-Throughput Combination Drug Screening. Science Translational Medicine. DOI: 10.1126/scitranslmed.aaw0064

About the National Center for Advancing Translational Sciences (NCATS):NCATS conducts and supports research on the science and operation of translation the process by which interventions to improve health are developed and implemented to allow more treatments to get to more patients more quickly. For more information about how NCATS is improving health through smarter science, visithttps://ncats.nih.gov.

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIHTurning Discovery Into Health

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Scientists find promising drug combination against lethal childhood brain cancers - National Institutes of Health

Autoimmune diseases are immune system disorders where the bodys immune system attacks its own tissues. Examples of common autoimmune diseases include rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, type 1 diabetes, multiple sclerosis (MS) and others.

A peculiarity of autoimmune diseases is that they have many genes in common, but they develop differently. For example, why does a patient with an autoimmune disease become a type 1 diabetic rather than have rheumatoid arthritis?

Decio L. Eizirik, a researcher at Universit Libre de Bruxelles Centre for Diabetes Research in Belgium, who is also a senior research fellow at the Indiana Biosciences Research Institute, recently published research in the journal Nature Genetics that found significant insight into this question. Eizirik took time to speak with BioSpace about the research and how a researcher in Belgium came to collaborate with researchers in Indiana, Spain, the UK and the U.S. National Institutes of Health.

Several autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis, multiple sclerosis, etc., have as much as 30 to 50% of their candidates genes in common, said Eizirik, raising the question on why in some individuals the immune system attacks, for instance, the insulin-producing beta cells, causing type 1 diabetes, while in others it targets joint tissues, leading to rheumatoid arthritis. Most of the research in the field has focused on the role for these candidate genes on the immune system, but our work indicated that many of these candidates genes affect the function and survival of pancreatic beta cells, leading to a misguided dialogue between them and the immune system that culminates in diabetes.

The early stages of type 1 diabetes, for example, show local autoimmune inflammation and progressive loss of the pancreatic beta cells that produce insulin. How these genetic transcription factors, or cytokines, interact with the beta-cell regulatory environment, and the changes that occur, suggest a key role in how the immune system gets triggered to attack the beta cells.

The research was conducted by Eizirik, Lorenzo Pasquali from the Institucio Catalana de Recerca I Estudis Avancats (ICREA) in Barcelona, Spain, and colleagues from Oxford, UK; Pisa, Italy, and the NIH. For about 20 years, Eizirik has run a diabetes-focused laboratory in Brussels. In August 2019, he launched a new laboratory at the IBRI, where, he said, three top scientists and assistants, Donalyn Scheuner, senior staff scientist at IBRI, Bill Carter, research analyst at IBRI, and Annie Rocio Pineros Alvarez, postdoctoral fellow in medicine at Indiana University, are already working. These two laboratories are working closely togetherfor instance, we have weekly meetings by videoconference, and besides my regular visits to the IBRI, scientists are moving between our European and USA labs on a temporary or permanent basis.

The IBIR was created by the State of Indiana and the states leading life science companies, academic research universities and medical school, as well as philanthropic organizations. The focus is on metabolic disease, including diabetes, cardiovascular disease obesity and poor nutrition. Its laboratories and offices are housed in about 20,000 square feet of space in Indian University School of Medicines Biotechnology Research and Training Center in Indianapolis. It expects to move into a new 68,000-square-feet site in mid-2020.

Eizirik said, The IBRI offers a unique opportunity to translate our basic research findings to the clinic, and we are working closely together with colleagues at Indiana University, particularly Carmella Evans-Molina, director of the Indiana Diabetes Research Center (IDRC) and the IDRC Islet and Physiology Core, to confirm our basic research findings in patients samples, and to eventually bring them to the clinic.

The specific research study looked at the binding of tissue-specific transcription factors. Transcription factors are basically proteins whose job it is to turn genes on or off by binding to DNA. So, for example, there are specific transcription factors whose job it is to regulate insulin production in pancreatic beta cells. In the case of this research, Eizirik and his team studied tissue-specific transcription factors that open the chromatin. Chromatin is a complex of DNA and protein found in the nucleus of the cell. It allows long DNA molecules to be packaged, typically in the form of chromosomes.

For gene transcription to occur, Eizirik said, chromatin must open and provide access to transcription factors. This allows binding of pro-inflammatory transcription factors induced in the beta cells by local inflammation.

For certain people who are genetically predisposed to type 1 diabetes, this leads to the generation of signals by the beta cells, Eizirik said, that contribute to attract and activate immune cells, rendering beta cells a potential target to the immune system.

Eizirik said, These observations have clarified the role for pancreatic beta cells in type 1 diabetes and provided an explanation for the reasons behind the immune system targeting beta cells.

The amplifying loop mechanism observed potentially explains other autoimmune diseases. Eizirik notes, Binding of tissue-specific transcription factors, within an inflammatory context and in genetically predisposed individuals, could generate signals that would attract and activate immune cells against specific target tissues.

Testing the theory in other autoimmune diseases will be required to verify it, but potentially could open up new therapies or preventive treatments for type 1 diabetes and other autoimmune diseases.

Type 1 diabetes has a strong genetic component, Eizirik said. At least 50% of the disease risk is due to genetic causesand understanding the role for candidate genes in the disease may point to novel therapies. For instance, up to now, nearly all therapeutic approaches to prevent type 1 diabetes have targeted the immune system, with little success. Our findings suggest that we must also take steps to directly boost beta cell survival.

He compared targeting the immune system only in type 1 diabetes to trying to fly a plane with only one wing. Our present and previous data suggest that we need two wings: first, to re-educate the immune system to stop its attack on the beta cells, and second, to increase the beta cell resistance to the immune attack, and to find means to restore the lost beta cell mass. Unfortunately, to achieve these goals in both type 1 diabetes and other autoimmune diseases is not easy, and we must redouble our efforts.

The next stages of the research will be to study the function of two novel candidate genes for type 1 diabetes that were discovered in the research. They both act at the beta cell level. He expects to conduct that research with Pasquali. The second stage is to evaluate the impact of other immune mediators that act earlier in the disease course at the beta cell level. And the third stage is to test their hypothesis regarding the role for the target tissue in other autoimmune diseases.

In addition to that ambitious agenda, Eizirik and his group are establishing an Inducible Pluripotential Cell Core at the IBRI.

Eizirik said, This will allow us to de-differentiate, for instance, skin cells from patients into pluripotential cells, and then to differentiate them into pancreatic beta cells. This will allow us to study the impact of the novel candidate genes we are discovering on beta cell function and survival, again in collaboration with Lorenzo Pasquali and Carmella Evans-Molina. This will also provide an excellent model to test new drugs to protect the beta cells in early type 1 diabetes.

See the article here:
Researchers Working to Understand Why Some Patients with Autoimmune Diseases Develop Diabetes Instead of Arthritis - BioSpace

A serving of Golden Rice contains half the beta-carotene children need daily.

By Erik StokstadNov. 20, 2019 , 3:00 PM

Soon. That has long been scientists' answer when asked about the approval of Golden Rice, a genetically modified (GM) crop that could help prevent childhood blindness and deaths in the developing world. Ever since Golden Rice first made headlines nearly 20 years ago, it has been a flashpoint in debates over GM crops. Advocates touted it as an example of their potential benefit to humanity, while opponents of transgenic crops criticized it as a risky and unnecessary approach to improve health in the developing world.

Now, Bangladesh appears about to become the first country to approve Golden Rice for planting. "It is really important to say we got this over the line," says Johnathan Napier, a plant biotechnologist at Rothamsted Research in Harpenden, U.K., who was not involved in the crop's development. He says approval would show that agricultural biotechnology can be successfully developed by publicly funded research centers for the public good. Still, environmental groups haven't dropped their oppositionand the first harvest isn't expected until at least 2021. And more research will be needed to show the extent of real-world benefits from Golden Rice.

Golden Rice was developed in the late 1990s by German plant scientists Ingo Potrykus and Peter Beyer to combat vitamin A deficiency, the leading cause of childhood blindness. Low levels of vitamin A also contribute to deaths from infectious diseases such as measles. Spinach, sweet potato, and other vegetables supply ample amounts of the vitamin, but in some countries, particularly those where rice is a major part of the diet, vitamin A deficiency is still widespread; in Bangladesh it affects about 21% of children.

To create Golden Rice, Potrykus and Beyer collaborated with agrochemical giant Syngenta to equip the plant with beta-carotene genes from maize. They donated their transgenic plants to public-sector agricultural institutes, paving the way for other researchers to breed the golden rice genes into varieties that suit local tastes and growing conditions.

Over the past 2 years, regulators in the United States, Canada, New Zealand, and Australia approved Golden Rice for consumption. There are no plans to grow the crop in these countries, but approval will prevent problems if Golden Rice somehow accidentally turns up in food supplies.

The Golden Rice under review in Bangladesh was created at the International Rice Research Institute (IRRI) in Los Baos, Philippines. Researchers bred the beta-carotene genes into a rice variety named dhan 29, which is grown widely during the dry season in Bangladesh and contributes about 14% of the national harvest. In tests of dhan 29 Golden Rice at multiple locations, researchers at the Bangladesh Rice Research Institute (BRRI) in Gazipur found no new farming challenges and no significant differences in qualityexcept for the presence of vitamin A.

BRRI submitted data to the Bangladeshi Ministry of Environment, Forest, and Climate Change in November 2017. The Biosafety Core Committee, a group of eight officials and scientists, has since been reviewing environmental risks, such as the plant's potential to become a weed, as well as food safety. The review is nearing completion; on 28 October, the Dhaka Tribune reported that a decision would be made by 15 November.

That date has come and gone; the holdup appears to be due to the death of a committee member. But a source familiar with the committee's deliberations says some members remain skeptical of Golden Rice, wondering for example why it is needed when people could also eat more vegetables.

Proponents are optimistic, however. The scientific evidence is strong, the committee previously approved another transgenic crop, and Golden Rice enjoys high-level political support in Bangladesh, they say. "We are hopeful that Golden Rice might get the green light soon," says Arif Hossain, director of Farming Future Bangladesh in Dhaka, which is funded by the Bill &Melinda Gates Foundation to inform policymakers and others about biotechnology.

After the environment ministry signs off, Golden Rice must be registered by a seed certification agency within the Ministry of Agriculture, which requires field trials in multiple places to test for seed quality. If all goes smoothly, farmers might have Golden Rice seed to plant by 2021.

How popular it will be is uncertain. Farmers in Bangladesh quickly adopted an eggplant variety engineered to kill certain insect pests after its 2014 introduction, but that crop offered an immediate benefit: Farmers need fewer insecticides. Golden Rice's health benefits will emerge more slowly, says agricultural economist Justus Wesseler of Wageningen University &Research in the Netherlands, so adoption may be slower as well. The government may need to promote Golden Rice and, Hossain says, even subsidize farmers to grow it.

Consumer acceptance may be another challenge, given the golden hue, says Sherry Tanumihardjo, who studies vitamin A and global health at the University of Wisconsin in Madison. "People have a difficult time changing the color of food they eat," and many people in Bangladesh prefer to eat white rice. On the other hand, cooked Golden Rice resembles khichuri, a popular dish of rice and lentils cooked with turmeric, which may increase its appeal. With Gates Foundation support, IRRI and BRRI are developing a strategy for directing farmers' harvest to rural regions and cities with high poverty and malnutrition rates.

Opposition from nongovernmental organizations could still hobble the introduction. Last month, two groups in Bangladeshthe Agricultural Farm Labour Federation and the National Women Farmers &Workers Associationcalled for a ban on both Golden Rice and transgenic eggplant.

If Golden Rice does make inroads in Bangladesh, additional varieties better adapted to other seasons or locations may follow. Bred at BRRI, they are now in greenhouse trials. Like all local versions of Golden Rice, these varieties were created not with genetic engineering, but by traditional backcrossing, so they will likely not need biosafety approval. "There will be no problem for a year-round supply of biofortified rice," says Partha Biswas, a plant breeder at BRRI.

But for now, all eyes are on dhan 29. "It would be great to see it approved," Napier says. "It's been a long time coming."

Read more:
Bangladesh could be the first to cultivate golden rice, genetically altered to fight blindness - Science Magazine

Last month, when Attorney General Bill Barr gave a speech at Notre Dame about religious liberty, I praised him for his take on the importance of religion to our Constitutional order, and for pointing fingers at those carrying out the organized destruction of religions place in the public square. I stand by that praise. But in his column today, taking on that speech, and a more recent one Barr delivered to the Federalist Society, about law and the presidency, Ross Douthat says the Attorney General is guilty of propping up Zombie Reaganism. Douthat writes:

What Barrs speeches presuppose, basically, is What if everything you believed before Trump, you can still believe today?

In the Notre Dame speech, this reassurance manifests itself in a restatement of the assumptions that have guided organized religious conservatism since the 1960s: that the chief threat to religious faith comes from secularizing elites; that the great moral debates of our time pit Christian rigorists on the right against moral relativists on the left; that religious conservatives and limited-government conservatives can be natural allies because the welfare state is an ersatz religious institution that crowds out private charity and churches.

Douthat goes on to say that Barrs diagnosis is correct, but limited in important ways. He goes on:

But theres no attempt in the speech to address the recent trends that complicate religious conservatisms 70s-era vision even though those trends helped make Barrs boss the president of the United States.

For instance, theres no mention of the extent to which conservative lawyers already won a series of battles against the harder sort of secularism even liberal jurisprudence today is less strictly secularist than in the 70s and it didnt matter much to the cultural erosion of their faith.

Theres no mention of how much of that erosion has happened under administrations friendly to conservative Christianity, and therefore probably reflects internal weakness, division and scandal more than pressure from outside. [Emphasis mine RD]

Theres no reckoning with the tension between the G.O.P.s religious and libertarian wings, the clear support of many religious conservatives for the welfare state that official conservatism decries or the extent to which Trump won the Republican nomination by running against the familiar critique of big government that Barr recycles in his speech.

Thats really true, and I wish I had caught that when I first wrote about Barrs speech. After all, I wrote a book based in large part on the fact that the culture has changed so much that its simply not plausible to believe that if only we elect the right politicians, we can re-Christianize the public square. The dog that did not bark was the Christian churches in the fight to preserve traditional marriage. In France secular France! almost a million people turned out in Paris to protest (unsuccessfully) the proposed pro-LGBT changes in the law. In America, nothing. In 1993, hundreds of thousands of gay folks turned out on the Mall in Washington, DC, to demand pro-LGBT laws. I was there covering the story. They cared enough to demonstrate; we conservative Christians did not. We thought having the right opinions, and voting Republican, and donating to conservative Christian PACs, would be enough.

Meanwhile, we lost the culture. Dont get me wrong, AG Barrs diagnosis is correct, as far as it goes. There really are elites doing their best to demonize Christian belief. But if thats the only diagnosis from the Right of our dire condition, it isnt enough. As Douthat points out later in his piece, after he issues a similar, even stronger, critique of Barrs speech on law and the imperial presidency, this rhetoric is the kind of thing that soothes conservative audiences but doesnt actually describe the world into which conservatives find themselves thrown in 2019.

Douthat points to Damon Linkers critique of Barrs Federalist Society speech, which Linker sees as a harbinger of future right-wing authoritarianism. Douthat is not quite buying it:

The other, which Im drawn to bymy own obsession with decadence, would emphasize futility instead. A conservatism that constantly reconverts itself to the worldview of the Reagan era isnt poised to claim sweeping, authoritarian power, in the service of religious revolution or any other cause. Its poised for repetition, gridlock and failure ever-imagining itself seizing the initiative, but really letting itself be carried backward, a boat against the current, into the world of Bill Barrs youth and past.

Douthat is consciously referring to the final line of The Great Gatsby:

Gatsby believed in the green light, the orgastic future that year by year recedes before us. It eluded us then, but thats no mattertomorrow we will run faster, stretch out our arms farther. . . . And one fine morning

So we beat on, boats against the current, borne back ceaselessly into the past.

Douthat is saying that Barrs two speeches are a form of willed optimism, of an old Reaganaut trying to convince himself and his listeners that its still 1980, and the Reagan-era verities still hold. Like Douthat, I am inclined to think of this in terms of decadence decadence not in the vulgar understanding of the term (e.g., licentiousness), but decadence in the sense of having no new ideas, and being compelled therefore to repeat old ones for lack of anything useful to say.Anyway, read the whole thing.

This is a problem on the Right, for sure. I think of the conservative Christians I know who are still captive to a more or less Reaganite view of the world, and who think that sending their kids to a Christian school, and attending a conservative Christian church, is sufficient to hold the line. They really do think that the line between good and evil is drawn between institutions and political parties.

I often return to this 1999 PBS Frontline episode, The Lost Children Of Rockdale County.My wife and I watched it when it was first aired, 20 years ago. Our firstborn child was not even one month old. It shocked us deeply. It made us vow that we would do everything we possibly could not to be parents like the Rockdale County moms and dads in this show. Heres a transcript of the program, and heres a link to a YouTube version.

The show takes an outbreak of syphilis among high schoolers in this upscale, politically conservative Atlanta suburb, and uses it to take a closer look at their lives. What they found, along with state health investigators, was a sexual free-for-all culture, abetted by the unwillingness of parents to pay close attention. From the transcript:

NARRATOR: There were lots of parties back then, anywhere that adults werent around. The kids would meet in empty homes all over Conyers, sometimes even in rented motel rooms. Kevin did not take part in their activities, but he knew about them.

KEVIN: There was a lot of sex going on then. Like, one girl would come in the group and shed be passed around, or one guy would go in the girls group and get passed around.

INTERVIEWER: Passed around?

KEVIN: Yeah, theyd just- one guy would do it with her one night. The next night somebody else has her. The next night somebody else has her.

INTERVIEWER: Was this a game?

KEVIN: Pretty much.

NICOLE: There was a lot of sex then, about 16 years old- a lot of sex. We would fight. There was about four of the guys that drove BMWs and had everything, and those were- all the girls wanted to be with those guys, so we would all fight over them or do whatever. And then youd have sex with them, so youd be, like, Yeah, I had sex with your man last night, da, da, da, do. And thats- I think thats how the syphilis came about. It was everybody just having sex with everybody.

D.J.: Actually, I mean, it was a social thing, but it was more of an underground railroad thing. Everybody was secretively having sex with everybody, and everybody knew it. The teenagers knew it. But the parents never knew.

Prof. CLAIRE STERK: A lot of the adolescents had parents who worked, were at home alone, had parents who put in 40, 60, 80-hour work weeks and were doing that to insure that all the resources that they wanted to give to their children were available.

BETH ROSS, Dir. Counseling, Rockdale County Schools: The activities they were involved in, whether it would be sexual or otherwise, the majority of their behavior was taking place between right after school and right before parents came home from work, like between 3:00 and 7:00, and some of it late at night then, after midnight, after the parents would go to sleep.

NICOLE: Most of my friends parents were not the kind of parents that really cared. They cared what went on, but if it interfered with their lives they didnt really- wouldnt- they didnt want to bother with it.

About halfway through the film, theres a town meeting with the parents to discuss the crisis:

Dr. KATHLEEN TOOMEY: What was so extraordinary to me is these parents started looking for externally who to blame. This has caused this, T.V. has caused that, External groups have caused this. But few of them none of them that I can recall ever looked to themselves. And the minister turned to me and said, They dont see. Its them. Its the parents. They have done this. The kids dont talk to them.

What was extraordinary to me, a year after this outbreak, was here was a community in total denial about what happened.

NARRATOR: In the end, the syphilis outbreak had come and gone, leaving barely a ripple behind. But some believe that the community, by regarding the outbreak as an anomaly, had missed a larger point about all its kids.

CLAIRE STERK: I would say its very sad because there are so many lessons we could have learned from this. And part of me feels that were not picking up on all those lessons and still leave adolescents hanging there, forcing them to take care of themselves when we know that theyre not always able to do that.

WES BONNER, Pastor: Theyre coming from middle class homes, upper middle class homes. They have so many things, you know, every convenience. They all have a cell phone, a pager, you know, anything that they need. But what theyre looking for is, you know, Wheres the road? Wheres the path? I dont see that. You know, everythings so spread out. I dont know, you know, where to go.

The children of Rockdale County are now parents. I wonder how theyre raising their kids? I wonder what narrative they tell themselves about life in America, to allow themselves to sleep at night? I wonder if theyre #MAGA nostalgists, or if theyre Silicon Valley Soixante-Huitards who believe that if we just tear down more barriers, then we will finally reach utopia.

Everybody in America is a nostalgist. Because we are a decadent society.

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Bill Barr's Blindness -- And Our Own - The American Conservative

Over the past ten days, a dozen current and former government officials have testified before the House impeachment inquiry. There is only one conclusion to be drawn from their hours of testimony: the president of the United States has repeatedly committed flagrantly impeachable offenses.

Donald Trump used the power of the presidency to extort a foreign government. He conditioned a White House visit for Ukraines new president and then later nearly $400 million dollars in military assistance on a public announcement of an investigation of former vice president Joe Biden, a key political rival.

As Gordon Sondland, US Ambassador to the European Union, testified on Wednesday, this was common knowledge within the Trump administration. Everyone, said Sondland, was in the loop.

Every witness offered clear and unambiguous evidence of this quid pro quo. To deny it happened is, quite simply, to deny reality.

And yet congressional Republicans appear intent on doing just that.

For all their sound and fury, GOP members offered the American people nothing that looked even remotely like a compelling defense of Trumps actions during the House impeachment inquiry. When they werent floating fantastical and evidence-free conspiracy theories about the Bidens, misplaced servers, and Ukrainian intervention in the 2016 election, they were spitting out one non sequitur argument after another.

They harped on the fact that Kyiv never actually investigated Biden willfully ignoring the presidents all-out campaign to win just such an investigation. Trump pulled numerous administration figures and his personal lawyer Rudy Giuliani into the shakedown campaign, and pressured the Ukrainian president, Volodymyr Zelensky, himself.

They said the president was worried about corruption in Ukraine disregarding the fact that he never once mentioned corruption in his calls with Zelensky and never once sought information from his own national security officials about Ukraines anti-corruption efforts.

They seized on the fact that none of the witnesses ever heard the president use the words bribery or extortion or specifically say he was conditioning military aid on a Biden investigation as if criminals regularly articulate their crimes and their precise motivations for committing them.

They said Ukraine eventually got their military assistance while remaining completely incurious about the fact that Trump delayed that aid for three months and only released it after the whistleblower complaint emerged. No Republican seriously questioned the fact that Trump made an investigation of Biden a condition for a White House visit by Zelensky which in of itself is a clear abuse of presidential power.

They misrepresented testimony and smeared witnesses. They railed against the whistleblower for offering second-hand evidence, oblivious to the individuals seated 20 feet in front of them who offered first-hand testimony. They hectored those who offered inconvenient evidence of the presidents guilt. They focused their questioning on individual trees while ignoring the vast and lush forest of presidential misconduct.

After nearly three years of Republicans defending Trumps corruption, his shredding of democratic norms, and his abuses of presidential power, none of us should be surprised.

But make no mistake, this latest cover-up is the nadir of Americas anti-democratic descent. Its not just that Trump sought to use his office for personal gain. Its that he tried to enlist a foreign government in influencing an American election just as he did with Russia in 2016.

When high crimes and misdemeanors as severe and profound as these can be summarily dismissed by members of the presidents own party; when the president can be shielded from accountability and, in effect, operate above the law; when he can openly seek to subvert elections without consequence, but rather with cheerleading, thats not democracy. Its authoritarian rule.

To some, this might sound like alarmism or hysteria. Its not.

The GOPs acquiescence to Trumps crimes should be a hair-on-fire moment for the American people a direct assault on the idea of the rule of law and a government of the people, by the people, and for the people.

What is even more terrifying is that Trump is probably a 50/50 bet to be re-elected. And if he wins, it would quite likely come once again with a victory in the Electoral College but a defeat in the popular vote.

If youve got a president twice-elected with a minority of votes, operating with virtual impunity, and using his office to pressure foreign governments to tarnish his political rivals, its not a sign of a healthy democracy. Rather, its a clear indication that Americas 243-year experiment in democratic governance is teetering on the brink. If Americans arent terrified of where all this is heading, they damn well should be.

Michael A. Cohens column appears regularly in the Globe. Follow him on Twitter @speechboy71.

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The GOP's willful blindness to Trump's abuses is putting our democracy in peril - The Boston Globe

DeAndre Hopkins helped the Houston Texans take control of the AFC South with a 20-17 win over the Indianapolis Colts on Thursday. He found the end zone twice and each time celebrated by giving the ball to a fan in the crowd. But it wasn't just any fan -- it was Hopkins' mother, Sabrina Greenlee, who is blind.

She always sits in the same seats at NRG Stadium during Texans home games. After hauling in the touchdown catch, Hopkins went right over to his mother and handed her the football. It's what he does whenever he scores during Texans homes games.

Greenlee has been blind since 2002, according to CBS KHOU. She was attacked by another woman who believed that Greenlee was sleeping with her boyfriend. Acid -- specifically a mix of bleach and lye -- was involved in the assault, which ultimately caused the blindness, and Greenlee was left in a coma for over two weeks. Although she attends nearly every Texans home game, she has never been able to see Hopkins, who was a rookie in 2013, play in the NFL.

Hopkins put on quite the performance for his mother with one of his best outings of the 2019 season. The Texans star wideout caught six passes for 94 yards and a pair of touchdowns, including a 30-yard strike from Deshaun Watson that ended up being the game-winning score. It was Hopkins' first multi-touchdown game since Houston's Week 1 contest against the New Orleans Saints.

Hopkins' huge performance gave the Texans the division lead and he was able to share one of his key touchdowns with his mother.

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Texans' DeAndre Hopkins gives two touchdown balls to his blind mom in heartwarming game tradition - CBS Sports

One of us is a liberal Democrat who voted for Hillary ClintonHillary Diane Rodham ClintonDemocratic strategist laments 'low bar' for Biden debate performance Wasserman Schultz makes bid for House Appropriations Committee gavel Trump to hold campaign rally in Pennsylvania next month MORE and learned about decoding Donald TrumpDonald John TrumpWatergate prosecutor says that Sondland testimony was 'tipping point' for Trump In private moment with Trump, Justice Kennedy pushed for Kavanaugh Supreme Court nomination: book Obama: 'Everybody needs to chill out' about differences between 2020 candidates MOREs words from his former attorney, Michael CohenMichael Dean CohenWill Republicans continue to engage in willful blindness? 3 reasons why impeachment fatigue has already set in Day 2 impeachment ratings drop by more than 1 million from first day MORE. The other is a conservative Republican who voted for Mr. Trump, served briefly as his White House communications director and thus also has experience trying to translate Trumps elliptical code words.

During the impeachment hearings so far, two Republican members of the House Intelligence Committee Reps. Jim JordanJames (Jim) Daniel JordanDiplomat seen rolling his eyes amid testy impeachment exchange with Jordan Live coverage: Impeachment spotlight shifts to Fiona Hill, David Holmes House GOP wants Senate Republicans to do more on impeachment MORE of Ohio and Elise StefanikElise Marie StefanikLive coverage: Impeachment spotlight shifts to Fiona Hill, David Holmes The Hill's Morning Report - Sondland stuns; Dems pull punches in fifth debate How House Republicans have stayed unified on impeachment MORE of New York were particularly ready to buy into these Trump code-word games.

Cohen, who served as Mr. Trumps attorney for 10 years, was quite experienced with Trumps reliance on code words, often hearing him use message words that were exactly the opposite of the truth.For example, in 2018, Cohen was asked by the Senate and House intelligence committees whether he had had discussions with Russians during the 2016 presidential campaign about the Trump Organization building a Trump Tower in Moscow. As Cohen subsequently testified, the answer was yes, and Trump was fully briefed. After receiving this question from the two committees, Cohen visited with Trump in the Oval Office to get guidance as to how he should answer. The code words were clear: Michael, no Russia, no discussions, no Russia, Trump told him. Cohen got the party-line message to lie, consistent with Trump's public denials during the campaign. (Cohen subsequently pled guilty and is serving prison time, in part as a result of following Trump's instructions-by-code to lie to Congress, knowing he was doing so for Trump's benefit.)

During last weeks televised impeachment hearings, committee Republicans accepted the truth of Trumps denials: No quid pro quo, no quid pro quo, no quid pro quo. They said there was no direct evidence of Trump linking military aid to Ukraine with requiring Ukraine's President Zelensky to announce corruption investigations of Democrats.

But what exactly did Trump say during his call with Zelensky? Wouldnt that be direct evidence?Lets re-read key parts of the summary transcript of the call.

First, the context: President Zelensky said his country was "almost ready to buy more Javelins" anti-tank missiles from the United States for defense purposes.

Trump then said,immediatelyafter Zelensky's reference to military weapons: "I would like you to do a favor though."

The word "though," in plain English, is the same as "but" or "however."

Then Trump immediately referenced the need to investigate the Democrats, based on the utterly debunked ultra-right conspiracy theory that Ukraine had the Democratic National Committee (DNC) server that had been hacked into by the Russians during the 2016 campaign. Trump mentioned the company, Crowdstrike, which helped the DNC to track the email hack to the Russians.

Then comes his direct ask:I would like you to find out what happened with this whole situation with Ukraine, they say Crowdstrike ... The server, they say Ukraine has it.

Note the words "I would like you to." This is more than just asking a "favor." It is consistent with Lt. Col. Vidman's interpretation at Tuesday's hearings that it sounds more like an "order" than asking for a "favor."

Just two paragraphs later in the summary transcript not more than a couple of minutes of conversation Trump mentions asecond favor to Zelensky. Specifically, Trump calls this the other thing.

Theres a lot of talk about Bidens son, that Biden stopped the prosecution and a lot of people want to find out about that so if you can look into it ... , he said.

Republicans try to deny the second favor but they are undone by the words the other thing. In the context of Zelensky asking for a shipment of Javelin missiles, Trump asks for two favors benefitting him personally and politically.

Trump has trouble pronouncing the three Latin words, quid pro quo. Here are three other Latin words that Republicans should recall when reading the summary transcript of the Trump-Zelensky July 25 call:"Res ipsa loquitur" "the thing speaks for itself."

Even indirect or so-called circumstantial evidence is still evidence that can lead to a conviction, based on a jurys reasonable inferences. We are compelled to ask Republicans: If you heard the Godfather telling his consiglieri, I dont like that guy, and shortly thereafter "that guy is shot, would you vote to acquit because there was no direct evidence of the Godfather giving the order?

We shall see whether Republicans will continue their willful blindness to the evidence, direct and circumstantial, until they will have to vote whether to impeach in the House and remove in the Senate. If they do, we shall see, about a year from now at the polls, whether Republicans engaging in such sophistry will be held accountable and sent back to private life.

Lanny Davis, an attorney in Washington, served as President Clintons special counsel from 1996 to 1998 and was a member of President George W. Bush's Privacy and Civil Liberties Oversight Board, 2006-07. He is a co-founder of the law firm of Davis Goldberg & Gaiper PLLC and the strategic media and public affairs firm Trident DMG. He authored "Crisis Tales: Five Rules for Coping with Crises in Business, Politics and Life" (2013). Follow him on Twitter @LannyDavis.

Anthony ScaramucciAnthony ScaramucciWill Republicans continue to engage in willful blindness? Scaramucci: Trump sees Bloomberg as threat Scaramucci: Trump will be gone by March 2020 MOREis an American entrepreneur, founder and co-managing partner of SkyBridge Capital. He served briefly as White House communications director. Follow him on Twitter@Scaramucci.

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Will Republicans continue to engage in willful blindness? | TheHill - The Hill

Scientists hope that the discovery of a sight-threatening genetic syndrome in monkeys could offer new avenues for developing treatments for the condition.

Writing in Experimental Eye Research, researchers highlight that three rhesus macaques monkeys were found to have Bardet-Biedl Syndrome (BBS), which leads to vision loss, kidney dysfunction and other symptoms.

BBS is part of a larger family of diseases that affect the retina called retinitis pigmentosa.

The syndrome occurs in one in 140,000 to 160,000 North American births.

Dr Martha Neuringer, from Oregon Health & Science University, highlighted that there is no cure for BBS at present.

Having a naturally occurring animal model for the condition could help us find one in the future, she shared.

Scientists also hope that having an animal model of BBS may lead to a greater understanding of a variety of retinitis pigmentosa diseases.

Image credit: Pixabay/christels

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Genetic condition that leads to blindness discovered in monkeys for the first time - AOP

Ritu Jha-

Dr. R.V. Ramani, managing trustee of Sankara Eye Foundation (SEF), one of the leading eye care service providers in India on being honored with the Padma Shri award [A Civilian Award bestowed by Govt.of.India]early this year says that these are moral boosters not only for the individuals but also for the organizations to which he or she belongs to.

It encourages you to do more and also encourages your confidence. There are people who appreciate the good things in life. So that is something that makes you feel positive about it.

Dr.Ramani was felicitated at the SEF USA annual banquet on Nov. 9 at Paradise Ballrooms in Fremont, California. Philanthropists, business and social leaders, and donors from the Indian-American community came together to celebrate the accomplishment of 1.96 million free eye surgeries through Sankara hospitals and over 80,000 free eye surgeries with their partner, as well as pledge support to fulfill the mission of eradicating curable blindness in India.

Dr. Ramani told indica with a smile on the sidelines of the conference, where people surrounded him congratulating him and taking a look at the prestigious Padma Shri medal he wore on his suit, You feel you were able to disseminate some good

It was a pleasant surprise; I wasnt aware of it, he said, on learning about the award.

The Sankara Eye Hospital was first established in 1977 to eliminate curable eye blindness in India, during his speech Dr. Ramani shared not just about his vision but about the upcoming hospitals in India as well as the use of technology, specifically artificial intelligence (AI) to ensure early diagnosis and prevention.

There are nine established super specialty SEF hospitals and three new SEF hospitals being built in Indore, Hyderabad, and Mumbai. Bihar Sankara Eye Hospital has partnered with Akhand Jyoti Hospital, based in Masti Chak, Bihar to help the underserved. The Sankara Eye Hospital in Indore is being inaugurated January 2020.

Dr. Ramani noted that Bihar has been slow with its establishment of SEF hospitals. He said the awareness is there but you need to create a sound foundation, that is why it took this much time. He believes to run an organization, one needs like-minded people. So together they aim and reach out to more people and be of service and disseminate role models so that more and more people will get on board.

On the usage of technology he said, Every day we see thousands of patients so data mining is going to help us a lot in the long term. Whatever we see and learn we try to integrate into future services.

It helps in both prevention and diagnosis. Preventative eye care for children and curative eye care for adults.

The annual banquet also held a panel conducted by Sridharan Krishnamurthy, president and board member of SEF USA where SEF India and its board members, share about why they joined Sankara and their work.

Bharath Balasubmaium, President Sankara Eye Hospital in Coimbatore, India told indica on how they are using Artificial Intelligence(AI) to take leverage of data generated through 10 hospitals said, weve started bringing technology 15 years back where weve revamped our client serve mechanism to data-based capturing mechanism. So, hospitals have been integrated and each hospital is connected and all the functional hospital generate data in real-time. And we monitor the progress of each location.

Balasubmaium, who has been associated for the past two decades with Sankara said in 2009, they ensured all hospitals should be integrated and data was visible and started researching AI to predict disease.

When asked how using AI, how its helping, he said to try to understand the reasons for the diseases and try to understand there are any patterns that have come out of the information that is available in the hospital data.

With the AI technology, which we have been developing for the past four years and have been trying to understand and come out the trends in diabetic retinopathy. We have patients with diabetes and so we are understanding the patterns and trends, Balasubmaium said.

Explaining further he said that with cataracts and now with diabetes increasing, diabetic retinopathy is becoming prevalent.

Lots of patients have a cataract, which is the leading cause of blindness, he said.

Balasubmaium also added that its not just the patients coming to the hospitals which generates data but also the people on the ground surveying in the field using the Sankara Electronic Remote Vision Information System (SERVIS) an app.

We are in the process of collecting the information and coming out with heat maps which have the job imaging in eye disease. Again, all this is real-time data collection

Balasubmaium says, with AI we are looking at what more can be done in preventing eye diseases.

The intention is to eliminate curable blindness, said Balasubmaium.

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Padma Shri Award Winner Dr. R.V. Ramani Speaks about the Role of Technology in Eliminating Curable Blindness - indica News

Timrepigene emparvovec is a potential first-in-class AAV2 gene therapy for the treatment of choroideremia, a rare, degenerative, X-linked retinal disorder that leads to blindness

CAMBRIDGE, Mass., Nov. 21, 2019 (GLOBE NEWSWIRE) -- Biogen Inc.(BIIB) announced today the enrollment of the last patient in the global Phase 3 STAR clinical study, which is evaluating the investigational gene therapy timrepigene emparvovec (BIIB111/AAV2-REP1) for the treatment of choroideremia (CHM). CHM is a rare, degenerative, X-linked inherited retinal disorder that leads to blindness.

We are excited to advance innovative investigational treatments for inherited retinal disorders that have significant unmet medical need due to the lack of treatment options, said Alfred Sandrock, Jr., M.D., Ph.D., Executive Vice President, Research and Development, and Chief Medical Officer at Biogen. Timrepigene emparvovec could be a transformative gene therapy for individuals living with choroideremia who would otherwise face inevitable blindness. Completing enrollment of our Phase 3 study represents a significant milestone in bringing this new potential therapy to patients.

STAR is a randomized, masked, prospective, parallel-controlled group Phase 3 study that enrolled 170 adult males with CHM. The study is evaluating the safety and efficacy of a single subretinal injection of timrepigene emparvovec. The primary endpoint is the proportion of patients with an improvement of at least 15 letters from baseline in best corrected visual acuity (BCVA) at 12 months post treatment as measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity protocol. The STAR study was initiated based on proof-of-concept data from Phase 1/2 studies, which indicated that at month 24, over 90 percent of patients treated with timrepigene emparvovec via targeted subretinal injection maintained visual acuity instead of experiencing the natural decline in BCVA expected in this degenerative disease. In a subset of treated patients with moderate to severe visual acuity loss, 21 percent experienced a gain in visual acuity of at least 15 ETDRS letters from baseline as compared to one percent of untreated patients in a natural history study.

CHM primarily affects males and is caused by a loss of function in the CHM gene which encodes the Rab escort protein-1 (REP-1). The REP-1 protein plays a role in intracellular protein trafficking, and the loss of function in the CHM gene leads to abnormal intracellular protein trafficking and impaired elimination of waste products from the retinal pigment epithelium and photoreceptors. Initially, patients with CHM experience poor night vision and over time, progressive visual loss ultimately leads to blindness.

Biogen added timrepigene emparvovec to its portfolio in June 2019 as part of its acquisition of Nightstar Therapeutics.

For more information about the Phase 3 STAR study, visit http://www.clinicaltrials.gov (NCT03496012).

About timrepigene emparvovec (BIIB111/AAV2-REP1)Timrepigene emparvovec is an AAV2 vector administered by subretinal injection, which aims to provide a functioning CHM gene and expression of the REP-1 protein to restore membrane trafficking and thereby slow, stop or potentially reverse decline in vision. Data from the Phase 1/2 studies demonstrated a slower rate of decline in visual acuity in patients treated with timrepigene emparvovec compared to untreated patients in the natural history study. In addition, some patients treated with timrepigene emparvovec showed improvements in visual acuity. The studies also demonstrated that timrepigene emparvovec was generally well tolerated with an acceptable safety profile.

Timrepigene emparvovec has received regenerative medicine advanced therapy (RMAT) designation from the U.S. Food and Drug Administration (FDA), which includes all of the benefits of the fast track and breakthrough therapy designation programs and orphan drug designations in the U.S., Europe and Japan. The safety and efficacy of a single subretinal injection of timrepigene emparvovec is currently being evaluated in the ongoing Phase 3 STAR study.

About Biogen At Biogen, our mission is clear: we are pioneers in neuroscience. Biogen discovers, develops, and delivers worldwide innovative therapies for people living with serious neurological and neurodegenerative diseases as well as related therapeutic adjacencies. One of the worlds first global biotechnology companies, Biogen was founded in 1978 by Charles Weissmann, Heinz Schaller, Kenneth Murray, and Nobel Prize winners Walter Gilbert and Phillip Sharp. Today Biogen has the leading portfolio of medicines to treat multiple sclerosis, has introduced the first approved treatment for spinal muscular atrophy, commercializes biosimilars of advanced biologics, and is focused on advancing research programs in multiple sclerosis and neuroimmunology, neuromuscular disorders, movement disorders, Alzheimers disease and dementia, ophthalmology, immunology, neurocognitive disorders, acute neurology, and pain.

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We routinely post information that may be important to investors on our website atwww.biogen.com. To learn more, please visitwww.biogen.comand follow us on social media Twitter,LinkedIn,Facebook,YouTube.

Biogen Safe Harbor StatementThis news release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, relating to the potential, benefits, safety and efficacy of timrepigene emparvovec; the potential clinical effects of timrepigene emparvovec; results from the Phase 1/2 studies of timrepigene emparvovec; the clinical development program for timrepigene emparvovec; the treatment of CHM; the potential of our commercial business and pipeline programs, including timrepigene emparvovec; and risks and uncertainties associated with drug development and commercialization. These forward-looking statements may be accompanied by words such as aim, anticipate, believe, could, estimate, expect, forecast, intend, may, plan, potential, possible, will, would and other words and terms of similar meaning. Drug development and commercialization involve a high degree of risk and only a small number of research and development programs result in commercialization of a product. Results in early stage clinical trials may not be indicative of full results or results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements, or the scientific data presented.

These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including without limitation, uncertainty of success in the development and potential commercialization of timrepigene emparvovec; unexpected concerns may arise from additional data, analysis or results obtained during the STAR study; regulatory authorities may require additional information or further studies, or may fail or refuse to approve or may delay approval of our drug candidates, including timrepigene emparvovec; the occurrence of adverse safety events; the risks of other unexpected hurdles, costs or delays; failure to protect and enforce our data, intellectual property and other proprietary rights and uncertainties relating to intellectual property claims and challenges; and product liability claims. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from our expectations in any forward-looking statement. Investors should consider this cautionary statement, as well as the risk factors identified in our most recent annual or quarterly report and in other reports we have filed with the U.S. Securities and Exchange Commission. These statements are based on our current beliefs and expectations and speak only as of the date of this news release. We do not undertake any obligation to publicly update any forward-looking statements, whether as a result of new information, future developments or otherwise.

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Biogen Announces Enrollment Completion of Global Phase 3 Gene Therapy Study for an Inherited Retinal Disorder - Yahoo Finance

This massive societal shift was met with backlash from some white citizens, who resented attempts at leveling the playing field through policies such as busing, racial quotas, affirmative action, and disparate-impact standards. They argued that these disruptive measures infringed on their personal liberties and had the effect of discriminating against them.

As desegregationist policies reached states and cities, white parents vacated public-school systems rather than integrate them, and the Supreme Court began hearing cases from white claimants who cited the unfairness of remedial policies governing hiring and promotion practices, university admissions, and government-contract allocations.

But the dynamics soon shifted. It wasnt long before those groups that were once making color-conscious arguments in support of racial segregation began using the principles of color-blind constitutionalism to assert that racially progressive policies were discriminating against white Americans.

Meanwhile, Thurgood Marshall ascended to the Court and grew dismayed that color blindness was now the main thrust of the legal argument against practical measures seeking to establish a racially egalitarian society. He wrote in his Regents of the University of California v. Bakke dissent, It is more than a little ironic that, after several hundred years of class-based discrimination against Negroes, the Court is unwilling to hold that a class-based remedy for that discrimination is permissible.

Adam Serwer: The Supreme Court is headed back to the 19th century

In Marshalls formulation, color-blind constitutionalism was a wholly appropriate approach for obtaining the equal rights of a subjugated people, but an insufficient guide to unmaking the societal disadvantages that racism had wrought. That is, he considered it in the words of the old gospel hymnIt once was blind, but now it sees.

This view accords with what scholars have long known. The political theorist Iris Marion Young argued that when unequal societies throw off statutory constraints and declare all citizens equals henceforth, preexisting group hierarchies are perpetuated unless proactively addressed. The upshot is that color-blind constitutionalism in unequal societies compels the lifting of state-sanctioned discrimination, but the ensuing remediation must be color-conscious in the same way that the harms were.

More recent conservative-leaning Supreme Courts seem to disagree. In a series of cases that tackle racial preferences and attempts at racial redress, the Court has found that a color-blind reading of the Constitution complicates or outright rejects color-conscious policies, even if they are implemented with the intent of furthering racial equality. For example, in Adarand Constructors, Inc. v. Pea (1995), a case challenging affirmative action in government contracts, the Court established that race-based classifications must meet strict scrutiny, the highest standard of judicial review. In Shelby County v. Holder (2013), the Court ruled that a measure intended to protect voters of color in jurisdictions with a history of racial discrimination was unconstitutional, effectively gutting the Voting Rights Act of 1965. The Court determined that Michigans affirmative-action ban was constitutional in Schuette v. Coalition to Defend Affirmative Action (2014).

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How Conservatives Turned the Color-Blind Constitution Against Racial Progress - The Atlantic

A group of teenage boys allegedly knocked a Philadelphia McDonald's worker unconscious after she wouldn't give them free food.

Charm Sullivan, 17, was working behind the counter at the McDonald's restaurant on Broad Street and Hunting Park on Wednesday night when the incident unfolded, her cousin Khadijah Lovett told NBC Philadelphia.

A group of boys asked her to give them free food. When Sullivan said no, at least four boys started to attack her, according to Lovett. The teenager tried to flee from the assailants by going to the bathroom at the store. But the boys followed her and continued their attack.

Lovett said the teens carried on beating the girl outside in the parking lot, where she was found unconscious between two cars. She claimed they "assaulted her several times," and hit her with a brick in front of the restaurant.

A photo of Sullivan seen by NBC shows her face with a severely swollen right eye, and red marks on her skin.

Sullivan went to hospital and returned home, before being sent back after she started to feel dizzy and threw up.

Lovett told NBC Philadelphia her cousin is "hurt" and will never return to work again.

"The only thing she keeps saying is she doesn't know. Why her. Why her?" she said. Lovett said of the culprits: "You're rude and you're ignorant and you're disrespectful and you wouldn't want nothing like this to happen to your mom, your sister."

The manager at the branch of McDonald's where Sullivan works refused to speak to NBC. McDonald's did not immediately respond to a request for comment from Newsweek.

Police have launched an investigation and are looking for the culprits.

Earlier this year in a separate attack in Australia, a McDonald's worker was blasted in the face with a fire extinguisher at a drive-thru, in an incident which could have left her "blinded."

In June, three males and one female drove up to the kiosk in a dark sedan at a Melbourne restaurant, staffed by Kimberley Friend, who was 21 at the time. The group taunted Friend, then drove away. Around 10 minutes later, they came back and a fire extinghuisher was let off in her face while others in the car filmed.

Friend told Australia's 9News at the time: "It [happened] so fast. I inhaled and tasted it straight away. [I thought], 'this is poison.'"

Her partner took her to a nearby hospital, where nurses told her the attack "could have caused blindness so, very lucky... it's not a joke, it was malicious," Friend said.

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Philadelphia Police Investigating Brutal Beating of McDonald's Worker Who Refused to Give Free Food to Teens - Newsweek

Prevent Blindness has declared December as Safe Toys and Gifts Awareness Month.

CHICAGO (PRWEB) November 21, 2019

Last year, the U.S. Consumer Product Safety Commission (CPSC) issued a report stating there were an estimated 251,700 toy-related injuries treated in U.S. hospital emergency departments. Forty-four percent of the estimated injuries were to the head and face area, the most commonly affected area of the body.

According to the CPSC, of the 251,700 estimated toy-related, emergency department-treated injuries, an estimated:

Prevent Blindness, the nations oldest non-profit eye health organization, has declared December as Safe Toys and Gifts Awareness month, to help shoppers select the best gifts for children.

For those considering purchasing sports equipment, Prevent Blindness suggests that the proper sports eye protection also be included. Recommendations may be found at http://www.preventblindness.org/recommended-sports-eye-protectors.

Sunglasses with UV protection can be a helpful gift for adults and children. Only buy sunglasses that provide a clear statement about how much UV radiation is blocked. The label should clearly state the sunglasses block 99 to 100 percent of UV-A and UV-B rays.

For all other gift ideas, Prevent Blindness recommends:

By taking a few cautionary steps to give gifts that are meaningful, safe and age-appropriate for children, you can help make sure that the holidays are festive and bright, said Jeff Todd, president and CEO of Prevent Blindness.

For more information on safe toys and gifts for children, please visit http://www.preventblindness.org/safe-toy-checklist or call Prevent Blindness at (800) 331-2020.

About Prevent Blindness Founded in 1908, Prevent Blindness is the nation's leading volunteer eye health and safety organization dedicated to fighting blindness and saving sight. Focused on promoting a continuum of vision care, Prevent Blindness touches the lives of millions of people each year through public and professional education, advocacy, certified vision screening and training, community and patient service programs and research. These services are made possible through the generous support of the American public. Together with a network of affiliates, Prevent Blindness is committed to eliminating preventable blindness in America. For more information, or to make a contribution to the sight-saving fund, call 1-800-331-2020. Or, visit us on the Web at preventblindness.org or facebook.com/preventblindness.

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An Estimated 184,000 Children, Under the Age of 15, Sent to the Emergency Room for Toy-related Injuries in One Year, According to the CPSC - PR Web

Cilia, or flagella whiplike appendages on cells perform diverse tasks required to keep the body healthy. When cilia malfunction, the consequences can be devastating, causing a range of problems, from blindness, to lung and kidney diseases, to congenital heart defects. Now, scientists have revealed the firstdetailed lookat the inner structure of cilia.

The newly revealed structure offers a starting point to begin exploring how cilia are assembled during development, how they are maintained over a cells life span, and how they might become dysfunctional if some of the cogs in these complex molecular machines are mutated or missing. The structure of these microscopic molecular machines common to cells in organisms from algae to people potentially will answer questions about human health and disease.

The research, by investigators at Washington University School of Medicine in St. Louis and Harvard Medical School, was published recently in the journal Cell.

This new study is exciting because it fills in a lot of missing information about the structure of cilia, said senior authorRui Zhang, assistant professor of biochemistry and molecular biophysics at Washington University. When cilia dont work properly, bad things happen. We need to know details of the structure in order to develop treatments for diseases, or strategies to prevent the developmental defects that can occur in the early embryo if the cilia are not functioning as they should.

In the respiratory tract, cilia move mucus and protect against viral and bacterial illnesses. In the reproductive tract, they propel sperm to fertilize an egg. Cilia also perform vital tasks in the brain, the kidney, the pancreas and in bone growth. And in the earliest stages of development, the rotational motion of specialized cilia in the embryo defines the bodys left-right asymmetry and where organs are placed. Without properly functioning cilia, the heart may not end up on the left side, where it should be, and it may not function properly.

Cilia are implicated in multiple human disorders, including polycystic kidney disease, which affects some 600,000 Americans and requires dialysis; primary ciliary dyskinesia, which causes chronic lung disease, misplaced organs and infertility; Bardet-Biedl syndrome, which causes patients to become blind in childhood and leads to diabetes, kidney disease and extreme obesity; and many congenital heart defects, which occur when left-right asymmetry goes awry and require complex surgeries to repair.

In the new study, the researchers used a technique called single particle cryo-electron microscopy to get a first look at 33 specific proteins arranged inside cilia within structures called ciliary microtubule doublets in a strict repeating pattern.

Before this work, everyone assumed these proteins inside cilia just stabilize the structure, which is true for a subset of the proteins, especially when you consider the forces produced by the continuous beating of the cilia, Zhang said. But based on how they are arranged inside this structure, we believe these proteins are doing many more things.

Since many of the proteins protrude through the cilia, Zhang and his colleagues speculate that they may allow for communication between the inside and the outside of the ciliary microtubule doublets; govern the function of enzymes that make important biochemical reactions possible; and sense changes in the calcium concentration of the environment, which plays a role in triggering the cilia to beat.

Among the proteins identified, five are associated with diseases that have been studied in mice and people, said co-authorSusan K. Dutcher, professor of genetics at Washington University. But until now, no one knew that these proteins were found inside cilia. We are just beginning to understand their roles in normal and disease states.

The researchers studied cilia in a type of algae calledChlamydomonas reinhardtii, which are single-celled organisms that have cilia structurally and biochemically similar to those of more complex organisms, including people. One question Dutcher is interested in answering is how the proteins making up cilia structure govern the type of motion that the cilia perform. The cilia of single-celledC. reinhardtiiare capable of more than one type of motion.

In some situations, the cilia are doing what you might consider a breast stroke, Dutcher said. In others, the motion is more of an S-shaped wave. The cilia of many cells in mammals can only produce one of these motions. But the single-celledC. reinhardtii, perhaps to help it adapt to its environment, can switch between them. Thats why were studying algae at a medical school the genetic problems we can study in the cilia of these organisms are similar to the ones that can occur in people, often with devastating consequences.

Zhang, Dutcher and their colleagues have plans to use the latest techniques of cryo-electron microscopy to study theChlamydomonas mutants of each of the 33 proteins inside cilia to seek answers to many questions that have arisen from this new and detailed knowledge of the structure.

Originally published by the School of Medicine

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Scientists unravel mysteries of cells' whiplike extensions | The Source - Washington University in St. Louis Newsroom