Genetics

PCOS subtypes associated with distinct genetic variations, finds study – News-Medical.Net

Researchers working on a National Institutes of Health (NIH) funded study found that polycystic ovary syndrome (PCOS) has distinct subtypes that are associated with genetic variations. Their study titled, "Distinct subtypes of polycystic ovary syndrome with novel genetic associations: An unsupervised, phenotypic clustering analysis," is published in the journal PLOS Medicine.

This study was funded by the NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Diabetes and Digestive and Kidney Diseases.

PCOS affects a large number of women, and authors of the study explain it as a "common, complex genetic disorder." They write that as many as 15 percent of women of reproductive age group suffer from this condition, and several diagnostic criteria can help in confirming the condition in a patient.

In women with PCOS, some of the common symptoms include irregular or missing periods, lack of or infrequent ovulation, raised levels of male sex hormones androgens in blood and associated features such as hirsutism or excessive facial hair. On ultrasound investigation, small cysts are detected on the surface of the ovaries. These women are at risk of being overweight and obese and may develop heart disease and type 2 diabetes and metabolic syndrome with time.

Image Credit: Marochkina Anastasiia / Shutterstock

There are several diagnostic criteria for the detection of PCOS. These are mainly based on expert opinions and consensus. Several controversies exist in these diagnostic criteria for PCOS, the team wrote.

There is a variation of physical features and physical symptoms among patients with PCOS. These are called phenotypic variations. In a recent study across populations with European ancestry, it was noted that the genetic makeup of women suffering from PCOS was distinctly similar despite being labeled using different diagnostic criteria. They write that this suggests that these diagnostic criteria "do not identify biologically distinct disease subtypes."

The objective of this study was thus to "test the hypothesis that there are biologically relevant subtypes of PCOS." Researcher Andrea Dunaif, MD, Chief of the Hilda and J. Lester Gabrilove Division of Endocrinology, Diabetes and Bone Disease at the Mount Sinai Health System, explained, "We're starting to make headway on what causes PCOS. It's very frustrating for patients because it's poorly understood, and patients often see several physicians before PCOS is diagnosed." Dunaif added, "Through genetics, we're beginning to understand the condition and may have specific targeted therapies in the not-too-distant future."

Study participants were a genotypical cohort. The biochemical data and the genotype data from these women was obtained from the "PCOS genome-wide association study (GWAS)." They made connections with the genotypes and the phenotypic or physical subtypes of the condition. A total of 893 women were included in the study. Their age range was between 25 and 32 years, and body mass index was between 28.2 and 41.5. These genotypic clusters were replicated in another cohort, which were not genotyped. Here there were 263 PCOS cases with an age range of 24 to 33 years and BMI ranging between 28.4 and 42.3.

On clustering analysis, the team found two distinct subtypes of PCOS. These were

On genotyping the initial cohort and dividing them into the two types of PCOS, several genetic characteristics were detected. The findings were:

A separate predictive model was developed to see if the cases tended to cluster in families. They found that 73 women with PCOS within an age range of 25 and 33 and BMI range of 27.8 and 42.3 kg/m2, usually "tended to cluster in families and that carriers of previously reported rare variants in DENND1A". The team wrote that this gene variant is known to regulate the synthesis of androgens or male hormones in the body.

The authors said that this initial study was conducted only among women with European ancestry who were diagnosed based on the National Institutes of Health (NIH) criteria. More extensive studies with a wide-ranging population would be more conclusive.

The researchers wrote that they "found reproducible reproductive and metabolic subtypes of PCOS," and these subtypes were "associated with novel, to our knowledge, susceptibility loci." They wrote that these subtypes had distinct genetic architecture.

Dr. Dunaif said, "In contrast to classifying disorders based on expert opinion, this is a very powerful objective approach to categorizing syndromes like PCOS into distinct subtypes with different causes, treatment, and clinical outcomes."

The team wrote, "Women with PCOS may be poorly served by being grouped under a single diagnosis because PCOS subtypes may differ in responses to therapy and in long-term outcomes."

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PCOS subtypes associated with distinct genetic variations, finds study - News-Medical.Net

Neuroscience

One-time treatment generates new neurons, eliminates Parkinson’s disease in mice – University of California

Xiang-Dong Fu, PhD, has never been more excited about something in his entire career. He has long studied the basic biology of RNA, a genetic cousin of DNA, and the proteins that bind it. But a single discovery has launched Fu into a completely new field: neuroscience.

For decades, Fu and his team at University of California San Diego School of Medicine studied a protein called PTB, which is well known for binding RNA and influencing which genes are turned on or off in a cell. To study the role of a protein like PTB, scientists often manipulate cells to reduce the amount of that protein, and then watch to see what happens.

Several years ago, a postdoctoral researcher working in Fus lab was taking that approach, using a technique called siRNA to silence the PTB gene in connective tissue cells known as fibroblasts. But its a tedious process that needs to be performed over and over. He got tired of it and convinced Fu they should use a different technique to create a stable cell line thats permanently lacking PTB. At first, the postdoc complained about that too, because it made the cells grow so slowly.

But then he noticed something odd after a couple of weeks there were very few fibroblasts left. Almost the whole dish was instead filled with neurons.

In this serendipitous way, the team discovered that inhibiting or deleting just a single gene, the gene that encodes PTB, transforms several types of mouse cells directly into neurons.

More recently, Fu and Hao Qian, PhD, another postdoctoral researcher in his lab, took the finding a big step forward, applying it in what could one day be a new therapeutic approach for Parkinsons disease and other neurodegenerative diseases. Just a single treatment to inhibit PTB in mice converted native astrocytes, star-shaped support cells of the brain, into neurons that produce the neurotransmitter dopamine. As a result, the mices Parkinsons disease symptoms disappeared.

The study is published June 24, 2020 inNature.

Researchers around the world have tried many ways to generate neurons in the lab, using stem cells and other means, so we can study them better, as well as to use them to replace lost neurons in neurodegenerative diseases, said Fu, who is a Distinguished Professor in the Department of Cellular and Molecular Medicine at UC San Diego School of Medicine. The fact that we could produce so many neurons in such a relatively easy way came as a big surprise.

There are several different ways to mimic Parkinsons disease in mice. In this case, the researchers applied a dopamine look-a-like molecule to poison neurons that produce dopamine. As a result, the mice lose dopamine-producing neurons and develop symptoms similar to Parkinsons disease, such as movement deficiencies.

The treatment works like this: The researchers developed a noninfectious virus that carries an antisense oligonucleotide sequence an artificial piece of DNA designed to specifically bind the RNA coding for PTB, thus degrading it, preventing it from being translated into a functional protein and stimulating neuron development.

Antisense oligonucleotides, also known as designer DNA drugs, are a proven approach for neurodegenerative and neuromuscular diseases study co-author, Don Cleveland, PhD, pioneered the technology, and it now forms the basis for a Food and Drug Administration (FDA)-approved therapy for spinal muscular atrophy and several other therapies currently in clinical trials. Cleveland is chair of the Department of Cellular and Molecular Medicine at UC San Diego School of Medicine and member of the Ludwig Institute for Cancer Research, San Diego.

The researchers administered the PTB antisense oligonucleotide treatment directly to the mouses midbrain, which is responsible for regulating motor control and reward behaviors, and the part of the brain that typically loses dopamine-producing neurons in Parkinsons disease. A control group of mice received mock treatment with an empty virus or an irrelevant antisense sequence.

In the treated mice, a small subset of astrocytes converted to neurons, increasing the number of neurons by approximately 30 percent. Dopamine levels were restored to a level comparable to that in normal mice. Whats more, the neurons grew and sent their processes into other parts of brain. There was no change in the control mice.

By two different measures of limb movement and response, the treated mice returned to normal within three months after a single treatment, and remained completely free from symptoms of Parkinsons disease for the rest of their lives. In contrast, the control mice showed no improvement.

I was stunned at what I saw, said study co-author William Mobley, MD, PhD, Distinguished Professor of Neurosciences at UC San Diego School of Medicine. This whole new strategy for treating neurodegeneration gives hope that it may be possible to help even those with advanced disease.

What is it about PTB that makes this work? This protein is present in a lot of cells, Fu said. But as neurons begin to develop from their precursors, it naturally disappears. What weve found is that forcing PTB to go away is the only signal a cell needs to turn on the genes needed to produce a neuron.

Of course, mice arent people, he cautioned. The model the team used doesnt perfectly recapitulate all essential features of Parkinsons disease. But the study provides a proof of concept, Fu said.

Next, the team plans to optimize their methods and test the approach in mouse models that mimic Parkinsons disease through genetic changes. They have also patented the PTB antisense oligonucleotide treatment in order to move forward toward testing in humans.

Its my dream to see this through to clinical trials, to test this approach as a treatment for Parkinsons disease, but also many other diseases where neurons are lost, such as Alzheimers and Huntingtons diseases and stroke, Fu said. And dreaming even bigger what if we could target PTB to correct defects in other parts of the brain, to treat things like inherited brain defects?

I intend to spend the rest of my career answering these questions.

Co-authors of the study include: Jing Hu, Dongyang Zhang, Zhengyu Liang, Fan Meng, Xuan Zhang, Yuanchao Xue, Steven F. Dowdy, Neal K. Devaraj, UC San Diego; Xinjiang Kang, Peking University, Liaocheng University; Roy Maimon, UC San Diego and Ludwig Institute for Cancer Research; and Zhuan Zhou, Peking University.

Funding for this research came, in part, from the National Institutes of Health (grants GM049369 and GM052872), Ludwig Institute for Cancer Research and Nomis Foundation, and Larry Hillblom Foundation.

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One-time treatment generates new neurons, eliminates Parkinson's disease in mice - University of California

Neuroscience

Sosei Heptares and AbbVie Announce New Discovery Collaboration Targeting Inflammatory Diseases – PharmiWeb.com

Tokyo, Japan and London, UK, 25 June 2020 Sosei Group Corporation (the Company; TSE: 4565) announces that it has entered into an exclusive discovery collaboration and option-to-license agreement with AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, to discover, develop and commercialize novel medicines that modulate G protein-coupled receptor (GPCR) targets of interest to AbbVie. The collaboration will initially focus on discovery of novel small molecules targeting inflammatory and autoimmune diseases.

Dr. Malcolm Weir, Executive Vice Chairman of Sosei Heptares, said: We are delighted to begin this new partnership with AbbVie, which further extends the application of our technology to novel and exciting targets, and we look forward building a close working relationship as the programs advance. Collaborating with leading pharmaceutical companies is a core element of our successful value-generating strategy. The ability to combine our unique technology and structure-based discovery and early development capabilities, particularly around challenging drug targets, with AbbVies extensive therapeutic area, development and global commercialization expertise is a powerful approach to creating new improved therapeutics for inflammatory and autoimmune diseases.

Dr. Lisa Olson, Vice President, Discover Immunology, AbbVie, said: Continued innovation across Immunology remains a key AbbVie priority. Combining AbbVies more than two decades of expertise in Immunology with researchers developing cutting-edge technologies best positions us to offer patients new hope for advanced, next-generation treatment for autoimmune diseases.

Sosei Heptares will apply its proprietary StaR technology and GPCR-focused Structure-based Drug Design (SBDD) capabilities and fund R&D activities through the completion of Investigational New Drug (IND)-enabling studies. AbbVie may then pay license fees to exercise its exclusive license options and assume responsibility for global development and commercialization.

Under the terms of the agreement, Sosei Heptares is eligible to receive up to US$32 million in upfront and near-term milestone payments, as well as potential option, development and commercial milestones of up to $377 million, plus tiered royalties on global commercial sales.

AbbVie has the option to expand the collaboration up to a total of four targets.

About AbbVie

AbbVie's mission is to discover and deliver innovative medicines that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas: immunology, oncology, neuroscience, eye care, virology, women's health and gastroenterology, in addition to products and services across its Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at http://www.abbvie.com. Follow @abbvie on Twitter, Facebook, Instagram, YouTube and LinkedIn.

About Sosei Heptares

We are an international biopharmaceutical group focused on the discovery and early development of new medicines originating from our proprietary GPCR-targeted StaR technology and structure-based drug design platform capabilities. We are advancing a broad and deep pipeline of novel medicines across multiple therapeutic areas, including CNS, immuno-oncology, gastroenterology, inflammation, and other rare/specialty indications.

We have established partnerships with some of the worlds leading pharmaceutical companies, including AbbVie, AstraZeneca, Genentech (Roche), Novartis, Pfizer and Takeda, and additionally with multiple emerging biotechnology companies. Sosei Heptares is headquartered in Tokyo, Japan with R&D facilities in Cambridge, UK.

Sosei Heptares is the corporate brand and trademark of Sosei Group Corporation, which is listed on the Tokyo Stock Exchange (ticker: 4565). Sosei, Heptares, the logo and StaR are trademarks of Sosei Group companies.

For more information, please visit https://www.soseiheptares.com/

LinkedIn: @soseiheptaresco | Twitter: @soseiheptaresco | YouTube: @soseiheptaresco

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Neuroscience

Senior Farewell: With appreciation for my first 18 years in Washington … and the four more years to come – Yakima Herald-Republic

Ive thought about writing this article for four years. One might assume I had an outline carefully prepared and ready to go, but such is not the case.

In my musings, I pictured my senior farewell article to be the capstone of four years of Unleashed, high school and extracurriculars, and my childhood in the Yakima Valley. But, I was wrong.

I had planned (loudly at times) to leave the state of Washington. College was going to be my ticket out of this mountain-dotted landscape we call home. I spent years envisioning what college would be like someplace far from here. I was enamored by the unknown. I couldnt have dreamed that 2020 would be so full of the unknown, even the unimaginable, no matter your physical location.

March brought a cacophony of unexpected events. My senior year went online, and I decided I would call the University of Washington my home for the next four years. Yes, you read that right: I will be attending college in-state, defying all of my expectations. As I delve into the inner workings of the brain as a neuroscience major, I hope to also deepen my understanding of the many reasons that make Washington a wonderful state to live. So, this farewell isnt a farewell at all; instead, its a documented account of why Im excited to live in the Pacific Northwest for four more years.

To start, I need to express my gratitude for my fellow Unleashed writers and this program as a whole. This group of brilliant reporters (including the alumni) are the most sincere and spirited lovers of the Yakima area I have ever met. My peers articles on community events and their experiences living in this Valley are endearing.

Next, thank you to my teachers who expressed, with great ardor, their love of the Yakima Valley. I am proud to be a Selah Viking.

Lastly, here is a list of the things I am grateful to have experienced in my first 18 years in the state of Washington:

Quarantine has taught me to embrace life with an open mind and heart. I am excited to spend time exploring this beautiful state Ive grown up in.

So, I have to be a fatalist: Attending the University of Washington wasnt what I imagined, but it is exactly where I need to be (except when Im back home visiting Yakima, of course).

Anna Ergeson is a 2020 graduate of Selah High School and a four-year member of the Yakima Herald-Republics Unleashed program. She plans to enroll this fall at the University of Washington as a presidential scholar majoring in neuroscience.

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Senior Farewell: With appreciation for my first 18 years in Washington ... and the four more years to come - Yakima Herald-Republic

Human Behavior

Stanford professor says rise in COVID-19 cases is proof that virus is tracking human behavior – KRON4

STANFORD, Calif. (KRON) There are several factors behind the rise in COVID-19 cases, including testing, contact tracing, and people interacting more as shelter-in place orders get relaxed.

But as we continue to track the virus a Stanford University professor says the new numbers are proof that the coronavirus is also tracking us.

I think the virus is tracking peoples behavior, Dr. Robert Siegel said.

Stanford University professor of microbiology and immunology Dr. Robert Siegel

says wear your mask, accounting for the recent rise in COVID-19 case numbers like this.

The virus would be very happy if we all went back and started socializing, Dr. Siegel said.

In other words, says Dr. Siegel, the virus doesnt care about what matters to people and that is the key to reopening.

The reopening is not working perfectly because as things open people are being more lax in their behavior like fewer people wearing masks, Dr. Siegel said.

Its called mask fatigue or quarantine fatigue.

Dr. Siegel points out that new cases are not spiking among one high risk group in particular, health care workers.

People are very carefully watching health care providers and their rate of infection is really, really low so they have a high exposure but they are being very careful and they are not getting infected, Dr. Siegel said.

If anything, Dr. Siegel says more testing is showing the recent uptick in cases is real.

He says there is scant evidence warmer weather has made much of a difference.

The key is, we have to continue to do the public health measures of wearing masks, social distancing and washing hands, using hand sanitizers and basically being smart, Dr. Siegel said.

Dr. Siegel says outsmarting the coronavirus starts with admitting that its still here and what you can do could save your life or someone elses life.

The virus is still very much present and you just have to look at the numbers, we are breaking records every day so in terms of risky behavior, you are more at risk for being in social settings without a mask than you ever were, Dr. Siegel said.

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Stanford professor says rise in COVID-19 cases is proof that virus is tracking human behavior - KRON4

Human Behavior

Racism: Its foundations may not be what you think they are – Washington Daily News – thewashingtondailynews.com

I recently received an email from the son of a Greenville friend who lives in Florida. The son was moved by the murder of George Floyd to initiate a new local program to reduce acts of racial prejudice through education, in hopes that education would change human behavior.

I applaud his efforts to make a difference. Would that more Americans would be stirred by the murders of black men to reduce racial hatred and prejudice. But I fear that education, alone, will is insufficient to address Americas original sin. It is difficult for me to imagine that after 400 years of prejudice and exploitation of African Americans in the land of the free there remains anyone unaware of the cruelty and viciousness with which black persons have been treated.

In 2016, Ibram X. Kendi addressed these issues in his National Book Award for Non-Fiction, Stamped from the Beginning. Kendis book traces the history of racist ideas in America, from colonial times to the present. During a recent book tour, he explained why education, alone, is inadequate for reducing racism: If the fundamental problem is ignorance and hate, then your solutions are going to be focused on education, and love and persuasion. But the actual foundation of racism is not ignorance and hate, but self-interest, particularly economic and political and cultural.

Self-interest, he added, drives racist policies that benefit that self-interest. When the policies are challenged because they produce inequalities, racist ideas spring up to justify those policies. Hate flows freely from there.

The first slaves to step foot on what would become American soil did so in the English settlement of Jamestown, Virginia, in 1619. Over the next decades, 400,000 more slaves joined them in the cotton, tobacco and sugar fields of southern planters interested in increasing profits. And what better way to cut costs than free labor?

By the 1800s, slavery had become the economic engine of the South, making it possible for planters to reap enormous profits. Self-interest motivated the heirs of those planters to succeed from the Union in 1860. And self-interest moved their descendants to deny civil rights to African Americans during the Jim Crow era.

In fact, throughout American history, racism has been used intentionally to preserve the privileged positions of white Americans. Since the very founding of the Republic, discrimination has been justified by those who benefit from it by appeals to pseudo-science, scriptures and other self-serving rationalizations that the black race is inferior by nature in intellect; that Africans were created by God to serve white Europeans; that the Bible supports slavery; that African Americans cannot compete with whites in school or work; that blacks are inherently violent and non-law abiding; and that all black men secretly desire to rape white women.

All of that, of course, is bunk. There is no verifiable evidence that Africans were or have ever been less intelligent than Europeans. Verses in the Bible that purport to legitimize slavery were cherry-picked and abused by Christian racists interested in providing scriptural cover for their right to own other human beings. Given a fair chance, there is no reason African Americans cannot compete with their white counterparts in school and work. Black neighborhoods are not more dangerous than white neighborhoods and neither are black people. And, to the consternation of members of the KKK and other white supremacist groups, black men do not rape white women near as often as white men do.

Prejudice against non-white peoples in America has existed for so long that it has become institutionalized. Practically every economic, political, social and, yes, religious institution in the USA continues to support racist policies, to varying degrees. Since the first European settlers landed on the shores of Virginia in 1608, the superiority of white European culture has been encoded in our customs, traditions and laws.

From housing to healthcare, policing to education, and banking to employment, America is a racist system that knows exactly what it is doing and does it successfully every day.

We cant educate our way out of something as structural, deeply embedded and systemic as American racism. No amount of education or love can eradicate the cancer that has been eating away at the body politic of America for more than 400 years.

On the contrary, efforts to reduce racism demand both honest recognition and our participation in a systemic response that changes the political, economic, social, cultural and religious policies that are the foundation of Americas foulest bias.

Polk Culpepper is a former Episcopal priest, retired lawyer and resident of Washington.

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Racism: Its foundations may not be what you think they are - Washington Daily News - thewashingtondailynews.com

Human Behavior

What went wrong in Arizona for COVID-19 cases to sky rocket? Experts weigh in – FOX 10 News Phoenix

What went wrong in Arizona for COVID-19 cases to sky rocket? Experts weigh in

Arizona is now a COVID-19 hot spot as cases and hospitalizations continue to break records nearly everyday. Some say the state has lacked direction from the governor, but are also saying young people are main drivers in the uptick.

PHOENIX - Arizona is now one of the worst coronavirus hotspots anywhere in the world. Per capita cases in the state are outpacing every country in Europe.

Health officials are now left with the question of, "What went wrong?"

In a Thursday news conference, Arizona Gov. Doug Ducey says this is Arizona's first wave of the virus as hospital beds arefilling up and restaurants are shutting down, again.

Thegovernor'soffice responded to this reportby saying,Wefollowedall CDC guidelines in trying to make the best decisions possible for the resident's of Arizona.

I think it starts at the top. I think that we havent seen great leadership at the top," saysDana Marie Kennedy, director at Arizona's AARP chapter.

RELATED:Gov. Ducey urges Arizonans to stay at home amid rising COVID-19 cases; expect hospital surge capacity

She demanded more safety and transparency months ago and even now sees a clear lack of leadership and communication illustrated by elected officials holding unmasking rallies.

She blames young adults for crowding into bars, too. In Arizona, I can go to a bar and nightclub tonight and have a great time. But what Icant do, is if my mom or grandmother was in a facility, I cannot go visit them," Kennedy said.

Arizona was also slow to start testing, and now people wait in line for hours for a test. Securing protective gear took too long as well.

The state never did mandate mask-wearing, but instead left it to local governmentsto decide.

RELATED:Arizona COVID-19 cases rise by over 3K for 4th day in week

The once fairly flat curve shot up, higher than New York ever saw.

The policy has to be aggressive enough that it influences human behavior in a way that is meaningful," saidWill Humble, former director of the Arizona Department of Health Services.

Gov.Ducey repeatedly saidan increase in cases was always expected.

We have an advantage over other states that had outbreaks early on. We have more time to prepare," Ducey said.

RELATED:Trump orders flags lowered to half-staff for three days for those who died from COVID-19

Even now, as other hotspots states like Texas and Florida scale back, Arizona is not.

The governor is instead asking people to stay home, like the order he lifted more than a month ago.

The valley is starting to see our first enforcement of large gatherings and social distancing. Several Scottsdale bars have been put on notice and will be closed for the weekend.

If mask-wearing is working,we should see the curve startto flatten againsometime in July.

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What went wrong in Arizona for COVID-19 cases to sky rocket? Experts weigh in - FOX 10 News Phoenix

Human Behavior

HBO Max’s magical and action-packed "Adventure Time" special is a tribute to heroic resistance – Salon

While watching the first installment ofHBO Max'sfour hour-long specials"Adventure Time: Distant Lands,"based on Pendleton Ward'sfantasy animated seriesthat ran on Cartoon Network, I was reminded of an episode from the show's fifth season. In the episode titled "BMO," the sentientgaming console voiced by Niki Yangaccidentally deletes their entire coresystemdrivers.sys during a round of routine maintenance. In order to operate as normal, BMO explains to Finn (Jeremy Shada) and Jake (John DiMaggio) that they'll need to trek out to the MO factory where BMO was "born."

Disguises are donned and shenanigans ensue, until BMO is finally reunited with their creator, Moseph "Moe" Mastro Giovanni, who proceeds to fix them. Moe reveals that BMO is very special. They were built as a companion for the child he never ended up having.

Moe explains, "I made BMO to be more."

In "Distant Lands," helmed by executive producer Adam Muto,BMO fully embraces that element of their design in their own special way. After 10 seasons of serving as a sidekick to Finn and Jake (albeit it an incredibly adorable and well-loved one), BMO steps into the role of hero by fighting the power of a broken system led by a corrupt ruler a narrative that is both universally timeless and incredibly timely.

BMO is happily shuttling through spacearmed with potatoes and a song about potatoes:"They're better than tomatoes!" on a mission to terraform Mars when they're suddelny thrown off course. BMO ends up on The Drift, a debilitated space station powered on-and-off by questionable energy sources and inhabited by colonies of scavengers. Watch the first four minutes below:

Thesociety is built on selling bits of valuable scrap to Hugo (Randall Park), a sketchy former Earthling who masterminds many of The Drift's mechanisms. BMO's crash-landingdestroys some valuable scrapping equipment that two groups The Great Elves and Shell People are feuding over, which then turns the conflict on BMO.

Before they can retaliate, BMO is swept up by Y4 (later renamed Y5), a young bunny-like creature (Glory Curda), who initially contemplates selling them to Hugo. But after BMO's quick thinking helps residents repair a breach and earns them the self-styled title ofsheriff, Y5 decides to become their playmate/deputy.

Together, they spend their days assisting Drift residents with day-to-day disasters like saving space beetles from drowning or wrangling space lard whileY5 is visibly weighed down by a sense of impending doom, as well as the vocal disapproval of her parents, who work for Hugo. As The Drift is becoming more and more unstable, it becomes increasingly apparent that Hugo is less of a reliable leader and more of a smarmy politician using the labor of the station's residents for his own selfish gain.

Inevitably, Y5 has to determine her own loyalties, while BMO remains undeterred from fighting against the injustice at play on The Drift.

"Even when things look really, really stupid, we still have to try," BMO says.

In this case, what is viewed as "stupid" on The Drift is voicing dissent especially as a child or a member of a marginalized community even when the people around you are apathetically falling in line.

And in this world, that so-called stupidityultimately makes a big difference.

"Adventure Time" has always succeeded in communicating a message without being moralistic, and this installment of "Distant Lands" is no different. This is partially because of, despite the absurdist environments, the show's very real depiction of human behavior and political machinations. When I watched Hugo boarding an escape pod despite cries of injustice, I couldn't help but think of Donald Trump retreating to the White House bunker while thousands took to the streets to protest racial inequality.

But just because "justice," however you define it, may not be immediately achieved, "Distant Lands" shows, through its depiction of BMO, that it's still something for which people should fight. "This robot expends energy in ways that yield it no benefit," observes Y5 at one point, perfectly encapsulating the generous heroism woven throughout the "Adventure Time" canon.

It's an almost childishly idealistic way to approach the universe, but after watching "Distant Lands," I realize that our world needs more BMOs because by embracing the philosophy to "be more," change can happen.

Thefirst installment of "Adventure Time: Distant Lands" is available to stream now on HBO Max. No release date has been announced for the following specials.

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HBO Max's magical and action-packed "Adventure Time" special is a tribute to heroic resistance - Salon

Human Behavior

Indias Economy : Aftermath of COVID19 – Observer Research Foundation

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This time it is truly different

Financial market punditry revels in truisms. One of them is the old chestnut about this time its different. There is an inherent, somewhat justified skepticism about this hypothesis, borne out by decades (sometimes centuries) of mean reversion. Most things, certainly financial market variables, tend to over time revert to an estimated mean (or average). However, this time it does seem rather different, at least different from what the generations living today have experienced.

The best-case scenario is the development of a vaccine or therapeutic soon enough. However, till a scalable solution is found, not only will large swathes of businessesrestaurants, hotels, airlinesbe wiped off, basic human behavior that underpins business and commerce will also change. As Prof. Kaushik Basu says, no economist writes down can talk as an assumption. It is regarded as a given. Being able to talk, walk up to the desk, argue and form relationships are core to how businesses are run take that away, and mankind needs a different paradigm to set the rules of business.

Social media tends to exaggerate political soundbytes. Despite all the noise on conflicts around the world (US-China, India-China, Afghanistan, Pakistan, Middle East), the world is a relatively peaceful place in terms of physical security. Warzones are few, hot conflicts engendering loss of civilian lives and properties are even fewer in the context of the 20th century history. There is however a distinct turn in economic behavior. The post-World War II journey towards greater integration of trade, openness to immigration, expansion of the global commons for business and commerce is being reversed. Protectionism has become a politically respected word in economic policy lexicon, and for good or for worse there is increasing resonance around the Thomas Piketty-style inequality stories.

Indias growth was slowing down in a secular trend even before the advent of COVID-19 and lockdown-related shocks. The slowdown has exacerbated the twin balance-sheet issue confronting India. This comprises stretched corporate leverage and concomitantly stressed bank (and Non Banking Financial Companies, or NBFC) balance sheets. Consequently, the financial systemwhich is the primary conduit and increasingly the primary source of intervention in the real economyis far too weak to effectively play a big part. 2020 was supposed to be a break-out yearaided by some global tailwinds and base effect, there was expectations of a bounce-back in growth. Unfortunately, COVID-19 put paid to those calculations. In short, India is faced with a double-jeopardy scenarioa weakening base of growth and a weakened set of financial institutions that are unable to front-load risk-taking. Add to it the unwillingness (or the inability) of the government to print money to take us out of this slowdown.

In this somewhat depressing scenario, there are some very important silver linings. They will be crucial for India to leverage while crafting a break-out strategy. For starters, the Foreign Exchange (Forex) constraint, one of Indias eternal constraints in economic policymaking, is largely absent. This is quite remarkable, given the worsening of external accounts of several Emerging Markets (EM) in the current crisis. Thanks to robust foreign equity flows, lower Current Account Deficit (CAD) and aggressive dollar buying by Reserve Bank of India (RBI), Indias Forex reserves today top US$500 billion. This providese a big policy cushionone that hasusually not been available to India during previous crises.

Second, nearly the entire public debt is financed via local savings, making it Indias unique strength for several decades now. There is no dependence, barring for tactical liquidity purposes in very small doses, on external foreign investment to fund Indias fiscal deficit (fisc). While the conventional commentaryincluding by Credit Rating Agencies (CRA)lament Indias high levels of sovereign debt, the fact is that the entire debt is financed locally. In other words, Indias public debt is financed by Indian Rupee (INR) capital, ie, in a currency which Government of India, the borrower, also enjoys a seigniorage (or power to print the currency) in.

While policy impulses, simplified tax regimes and all that passes off as reforms can play a part, the real heavy lifting in a post-COVID-19 strategy has to be government spending. With private discretionary consumption likely to remain muted for some time, private corporate sector investment would likely take longer, and global trade and commerce remaining both slow and mired in the new protectionist debatesgovernment spend is the only viable game in town. Its not a surprise therefore to see the level of fiscal stimuli announced in several countries around the world, going up to as much as 10-20% of gross domestic product (GDP). The Indian fiscal intervention, till now, has been small and cautious. But there have been promises of more as the lockdown is lifted. It is really not an option, so the question around a bigger fiscal push has to be a question of when rather than if.

For the government to spend more, a viable financing plan is a sine qua non. Globally, developed countries are financing enhanced fisc via money-printing programmes (also called Quantitative Easing, or QE). India has the same option too, but (till now) has been strangely recalcitrant about exercising it. There is a fear that printing money will cause a run on the currency, with all its attendant issues. But given that India funds all its public debt via local savings (as discussed above), it is a risk that exists more in theory than in realms of plausible reality. Unless the government spending program sends the CAD sky-rocketing, there is very little risk to a wholesale devaluation of the currency. However, it is a fact that the government has held back on exercising this option.

The other option to fund an expanded fisc, with a fair assumption that tax revenues are going to fall short, is via an aggressive asset sales program. A fire sale of state assets is not usually a great strategy for managing taxpayer-owned assets, but if the expenditure is focused on creating new infrastructure assets, it would only mean swapping one type of public assets with another. In other words, if proceeds from (the planned) LIC stake sale are used to create (say) 5 new hospitals, it isnt really a dilution of taxpayer-ownership of economy, but merely swapping LIC shares for hospital ownership.

Maybe a variant of the Hobsons choice, but a choice that needs to be exercised.

For a very long time, inflation has been a primary concern for economic policymaking. This is driven by the importance of inflation in our political economy discourse. In recent times, India has sought to embrace a low inflation mantra as some sort of axiomatic truism. It climaxed into the Inflation Targeting law that formally gave the RBI an inflation target as its primary objective in policymaking. While it meant that India has seen record low average inflation rates for the last few years, it has also disturbed several other economic outcomes. Lower inflation has meant lower nominal GDP growth; this is the reason why a 6-7% growth in recent times didnt seem to feel like the 6-7% growth we saw earlier. Sans a higher nominal GDP growth, incomes dont grow as fast, demand doesnt go up as fast, tax revenues dont grow as fast. More importantly a higher inflation allows the government to inflate away debt faster and creates greater headroom for more debt to be taken for higher growth in the future.

Today, when the primary issue confronting us is a massive demand destruction, inflation is bound to trend lower. This could have the effect of a disastrous spiral as government is unable to mop up enough revenues, and also unable to raise more debt as underlying GDP nominal growth remains weak.

A variety of policy toolsfrom direct income support to dilution of Inflation Targeting mandate to RBI need to be used to ensure that Indias inflation remains solidly positive.

An era is fading away. An era of expanding global commons, free trade and global prosperity. The new era might well end up being a more dog-eat-dog world. But Indias opportunities remain immense not only because of its oft-repeated strengths of young population and big middle class. Our silver linings are bright, and COVID-19 has not destroyed our physical infrastructure. But government policymaking needs to be quick, adaptive and decisive if we are to escape a prolonged growth funk, something that India can ill-afford.

The rest is here:
Indias Economy : Aftermath of COVID19 - Observer Research Foundation

Human Behavior

Tweeting Our Way Through A Pandemic – American Council on Science and Health

The researchers made use of two datasets. C-Span provided information on the verified Twitter accounts of the members of the 116thCongress; Twitters interface provided the tweets. Using machine learning and algorithms, the researchers created a dataset linking each Congressperson with their COVID-19 related tweets and then went on to characterize the word frequency of those tweets. Using word frequency, how often a given word appears in a document, has, for some time, been a tool of scientists looking to understand our speech. It has been used to differentiate one writer from another. In this instance, they used word frequency to characterize all of the Congressional tweets from January 17thwhen COVID-19 was first mentioned until March 31st roughly three weeks after COVID-19 was declared a national emergency.

As the graphic demonstrates, Democrats and Republicans chose very different words to their perception of the pandemic. For example, crisis was used 7% more often by the Democrats while China was mention 5% more by Republicans. Democrats also were more likely to tweet about COVID-19 than their Republican counterparts. For every 45 Republican Congressional tweets, there were 71 tweets from the Democrats

To get a better handle on the possible polarization between the two parties, the researchers using these word frequencies sought to identify whether the tweet was from a Democrat or Republican. The idea was the more often they were correct in their identification, the more the tweet reflected the Republican or Democratic word choices, their language polarization, and the more the member of Congress reflected their partys viewpoint. The algorithm they developed correctly identified 70% of the tweets political party.

Polarization, as measured in this manner, changed over time. While it was initially low, meaning that the algorithm had difficulty correctly identifying Democratic from Republican tweet, but by February 9th,it quickly peaked partisan camps were fully formed. With a small decline in the next few weeks, polarization again rose as various relief packages were being considered, mid-March. Nearly 70% of tweets no longer shared common word choices, so not only were partisan camps formed, but in some senses, the lines were clearly drawn between the two.

Democrats discussing the issue earlier, more frequently, and with more emphasis on public health and direct aid to affected workers. By contrast, Republicans placed more emphasis on generalized national unity, China, and businesses.

What can we make of these findings? At a minimum, we see that tweets are reflective of political opinion and that our Congress failed to achieve any consensus on how best to manage this pandemic because they quickly viewed the situation through a political, partisan lens. As the researchers point out, this failure of consensus resulted in an un-coordinated governmental response at both the agency and cueing level by cueing, I refer to the examples set by our leadership over what to do personally.

We would like to believe that science, deductive reasoning with a multiplicity of proofs and refutations, is value-free. To a large extent, that may be truer in some fields like physics or chemistry. But science is grounded in our culture; for example, the traditional Eastern science of medicine differs quite a bit from that of Western medical science. When we are dealing with a science that is heavily entangled with human behavior, as is public health epidemiology, we do ourselves a disserve in not recognizing that aspect and taking it into account.

As the blame game continues over which faceless agency dropped the ball or offered misleading information it is worth taking a moment and considering the role of our elected leadership, not merely the President and the executive branch, but the legislative branch that provides the financial means for the executive to act. The responsibility for the failures to protect public health and the economy lies as much with our leadership as with the regulatory bodies, they seek to blame and shame. Might I suggest that as you decide who will be your local and Congressional representatives in the upcoming year, you consider how well they led and protected you during this time rather than make a choice on what they promise to do in the future.

Source: Elusive consensus: Polarization in elite communications on the COVID-19 pandemic Science Advances DOI: 1 0.1126/sciadv.abc2717

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Tweeting Our Way Through A Pandemic - American Council on Science and Health