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Archive for April, 2020

Gods of genetic engineering: With the end of ‘Homo sapiens naturalis’ approaching, what is our place in nature? – Genetic Literacy Project

Friday, April 24th, 2020

Our society has evolved so much, can we still say that we are part of Nature? If not, should we worry and what should we do about it? Poppy, 21, Warwick.

Such is the extent of our dominion on Earth, that the answer to questions around whether we are still part of nature and whether we even need some of it rely on an understanding of what we want as Homo sapiens. And to know what we want, we need to grasp what we are.

It is a huge question but they are the best. And as a biologist, here is my humble suggestion to address it, and a personal conclusion. You may have a different one, but what matters is that we reflect on it.

Perhaps the best place to start is to consider what makes us human in the first place, which is not as obvious as it may seem.

Many years ago, a novel written by Vercors called Les Animaux dnaturs (Denatured Animals) told the story of a group of primitive hominids, the Tropis, found in an unexplored jungle in New Guinea, who seem to constitute a missing link.

However, the prospect that this fictional group may be used as slave labor by an entrepreneurial businessman named Vancruysen forces society to decide whether the Tropis are simply sophisticated animals or whether they should be given human rights. And herein lies the difficulty.

Human status had hitherto seemed so obvious that the book describes how it is soon discovered that there is no definition of what a human actually is. Certainly, the string of experts consulted anthropologists, primatologists, psychologists, lawyers and clergymen could not agree. Perhaps prophetically, it is a layperson who suggested a possible way forward.

She asked whether some of the hominids habits could be described as the early signs of a spiritual or religious mind. In short, were there signs that, like us, the Tropis were no longer at one with nature, but had separated from it, and were now looking at it from the outside with some fear.

It is a telling perspective. Our status as altered or denatured animals creatures who have arguably separated from the natural world is perhaps both the source of our humanity and the cause of many of our troubles. In the words of the books author:

All mans troubles arise from the fact that we do not know what we are and do not agree on what we want to be.

We will probably never know the timing of our gradual separation from nature although cave paintings perhaps contain some clues. But a key recent event in our relationship with the world around us is as well documented as it was abrupt. It happened on a sunny Monday morning, at 8.15am precisely.

The atomic bomb that rocked Hiroshima on August 6 1945, was a wake-up call so loud that it still resonates in our consciousness many decades later.

The day the sun rose twice was not only a forceful demonstration of the new era that we had entered, it was a reminder of how paradoxically primitive we remained: differential calculus, advanced electronics and almost godlike insights into the laws of the universe helped build, well a very big stick. Modern Homo sapiens seemingly had developed the powers of gods, while keeping the psyche of a stereotypical Stone Age killer.

We were no longer fearful of nature, but of what we would do to it, and ourselves. In short, we still did not know where we came from, but began panicking about where we were going.

We now know a lot more about our origins but we remain unsure about what we want to be in the future or, increasingly, as the climate crisis accelerates, whether we even have one.

Arguably, the greater choices granted by our technological advances make it even more difficult to decide which of the many paths to take. This is the cost of freedom.

I am not arguing against our dominion over nature nor, even as a biologist, do I feel a need to preserve the status quo. Big changes are part of our evolution. After all, oxygen was first a poison which threatened the very existence of early life, yet it is now the fuel vital to our existence.

Similarly, we may have to accept that what we do, even our unprecedented dominion, is a natural consequence of what we have evolved into, and by a process nothing less natural than natural selection itself. If artificial birth control is unnatural, so is reduced infant mortality.

I am also not convinced by the argument against genetic engineering on the basis that it is unnatural. By artificially selecting specific strains of wheat or dogs, we had been tinkering more or less blindly with genomes for centuries before the genetic revolution. Even our choice of romantic partner is a form of genetic engineering. Sex is natures way of producing new genetic combinations quickly.

Even nature, it seems, can be impatient with itself.

Advances in genomics, however, have opened the door to another key turning point. Perhaps we can avoid blowing up the world, and instead change it and ourselves slowly, perhaps beyond recognition.

The development of genetically modified crops in the 1980s quickly moved from early aspirations to improve the taste of food to a more efficient way of destroying undesirable weeds or pests.

In what some saw as the genetic equivalent of the atomic bomb, our early forays into a new technology became once again largely about killing, coupled with worries about contamination. Not that everything was rosy before that. Artificial selection, intensive farming and our exploding population growth were long destroying species quicker than we could record them.

The increasing silent springs of the 1950s and 60s caused by the destruction of farmland birds and, consequently, their song was only the tip of a deeper and more sinister iceberg. There is, in principle, nothing unnatural about extinction, which has been a recurring pattern (of sometimes massive proportions) in the evolution of our planet long before we came on the scene. But is it really what we want?

The arguments for maintaining biodiversity are usually based on survival, economics or ethics. In addition to preserving obvious key environments essential to our ecosystem and global survival, the economic argument highlights the possibility that a hitherto insignificant lichen, bacteria or reptile might hold the key to the cure of a future disease. We simply cannot afford to destroy what we do not know.

But attaching an economic value to life makes it subject to the fluctuation of markets. It is reasonable to expect that, in time, most biological solutions will be able to be synthesized, and as the market worth of many lifeforms falls, we need to scrutinize the significance of the ethical argument. Do we need nature because of its inherent value?

Perhaps the answer may come from peering over the horizon. It is somewhat of an irony that as the third millennium coincided with decrypting the human genome, perhaps the start of the fourth may be about whether it has become redundant.

Just as genetic modification may one day lead to the end of Homo sapiens naturalis (that is, humans untouched by genetic engineering), we may one day wave goodbye to the last specimen of Homo sapiens genetica. That is the last fully genetically based human living in a world increasingly less burdened by our biological form minds in a machine.

If the essence of a human, including our memories, desires and values, is somehow reflected in the pattern of the delicate neuronal connections of our brain (and why should it not?) our minds may also one day be changeable like never before.

And this brings us to the essential question that surely we must ask ourselves now: if, or rather when, we have the power to change anything, what would we not change?

After all, we may be able to transform ourselves into more rational, more efficient and stronger individuals. We may venture out further, have greater dominion over greater areas of space, and inject enough insight to bridge the gap between the issues brought about by our cultural evolution and the abilities of a brain evolved to deal with much simpler problems. We might even decide to move into a bodiless intelligence: in the end, even the pleasures of the body are located in the brain.

And then what? When the secrets of the universe are no longer hidden, what makes it worth being part of it? Where is the fun?

Gossip and sex, of course! some might say. And in effect, I would agree (although I might put it differently), as it conveys to me the fundamental need that we have to reach out and connect with others. I believe that the attributes that define our worth in this vast and changing universe are simple: empathy and love. Not power or technology, which occupy so many of our thoughts but which are merely (almost boringly) related to the age of a civilization.

Like many a traveler, Homo sapiens may need a goal. But from the strengths that come with attaining it, one realizes that ones worth (whether as an individual or a species) ultimately lies elsewhere. So I believe that the extent of our ability for empathy and love will be the yardstick by which our civilization is judged. It may well be an important benchmark by which we will judge other civilizations that we may encounter, or indeed be judged by them.

There is something of true wonder at the basis of it all. The fact that chemicals can arise from the austere confines of an ancient molecular soup, and through the cold laws of evolution, combine into organisms that care for other lifeforms (that is, other bags of chemicals) is the true miracle.

Some ancients believed that God made us in his image. Perhaps they were right in a sense, as empathy and love are truly godlike features, at least among the benevolent gods.

Cherish those traits and use them now, Poppy, as they hold the solution to our ethical dilemma. It is those very attributes that should compel us to improve the wellbeing of our fellow humans without lowering the condition of what surrounds us.

Anything less will pervert (our) nature.

Manuel Berdoy is a biologist at the University of Oxford

A version of this article originally appeared on The Conversation and has been republished here with permission. The Conversation can be found on Twitter @ConversationUS

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Gods of genetic engineering: With the end of 'Homo sapiens naturalis' approaching, what is our place in nature? - Genetic Literacy Project

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Reversing diabetes with CRISPR and patient-derived stem cells – FierceBiotech

Friday, April 24th, 2020

Insulin injections cancontrol diabetes, but patients still experience serious complications such as kidney disease and skin infections. Transplanting pancreatic tissues containing functional insulin-producing beta cells is of limited use, because donors are scarce and patients must take immunosuppressant drugs afterward.

Now, scientists atWashington University in St. Louis havedeveloped a way to use gene editing system CRISPR-Cas9 to edit a mutation in human-induced pluripotent stem cells (iPSCs) and then turnthem into beta cells. When transplanted into mice, the cells reversed preexisting diabetes in a lasting way, according to results published in the journal Science Translational Medicine.

While the researchers used cells from patients with Wolfram syndromea rare childhood diabetes caused by mutations in the WFS1 genethey argue that the combination of a gene therapy with stem cells could potentially treat other forms of diabetes as well.

Virtual Clinical Trials Online

This virtual event will bring together industry experts to discuss the increasing pace of pharmaceutical innovation, the need to maintain data quality and integrity as new technologies are implemented and understand regulatory challenges to ensure compliance.

One of the biggest challenges we faced was differentiating our patient cells into beta cells. Previous approaches do not allow for this robust differentiation. We use our new differentiation protocol targeting different development and signaling pathways to generate our cells, the studys lead author, Kristina Maxwell, explained in a video statement.

Making pancreatic beta cells from patient-derived stem cells requires precise activation and repression of specific pathways, and atthe right times, to guide the development process. In a recent Nature Biotechnology study, the team described a successful method that leverages the link between a complex known as actin cytoskeleton and the expression of transcription factors that drive pancreatic cell differentiation.

This time, the researchers applied the technology to iPSCs from two patients with Wolfram syndrome. They used CRISPR to correct the mutated WFS1 gene in the cells and differentiated the edited iPSCs into fully functional beta cells.

After transplanting the corrected beta cells into diabetic mice, the animals saw their blood glucose drop quickly, suggesting the disease had been reversed. The effect lasted for the entire six-month observation period, the scientists reported. By comparison, those receiving unedited cells from patients were unable to achieve glycemic control.

RELATED:CRISPR Therapeutics, ViaCyte team up on gene-edited diabetes treatment

The idea of editing stem cells with CRISPR has already attracted interest in the biopharma industry. Back in 2018, CRISPR Therapeutics penned a deal with ViaCyte to develop off-the-shelf, gene-editing stem cell therapies for diabetes. Rather than editing iPSCs from particular patients themselves to correct a faulty gene, the pairs lead project used CRISPR to edit healthy cells so that they lackedthe B2M gene and expressed PD-L1 to protect against immune attack. The two companies unveiled positive preclinical data inSeptember.

Other research groups working on gene therapy or stem cells for diabetes include a Harvard University scientist and his startup Semma Therapeutics, whichdeveloped a method for selecting beta cells out of a mixture of cells developed from PSCs. Scientists at the University of Wisconsin-Madison recently proposed that removing the IRE1-alpha gene in beta cells could prevent immune T cells from attacking them in mice with Type 1 diabetes.

The Washington University team hopes its technology may help Type 1 diabetes patients whose disease is caused by multiple genetic and environmental factors as well as the Type 2 form linked to obesity and insulin resistance.

We can generate a virtually unlimited number of beta cells from patients with diabetes to test and discover new drugs to hopefully stop or even reverse this disease, Jeffrey Millman, the studys co-senior author, said in the video statement. Perhaps most importantly, this technology now allows for the potential use of gene therapy in combination with the patients own cells to treat their own diabetes by transplantation of lab-grown beta cells.

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How effective is PLX cell therapy in treating coronavirus? Experts answer all queries and more – India TV News

Friday, April 24th, 2020

Pluristem Therapeutics or PLX cell therapyuses placentas to grow smart cells, and programs them to secrete therapeutic proteins in the bodies of sick people. It has just treated its first American COVID-19 patient after treating seven Israelis. The patients were suffering from acute respiratory failure and inflammatory complications associated with Covid-19. Now, this theraphy is being touted as a possible 'cure'' for the deadly coronavirus with scientisst conducting varied researches on the same. In an exclusive interaction with India TV, doctors from India and abroadcame together for discussing about how effective can cell therapy be in treating coronavirus. Dr Solomon from Israel, Dr Anil Kaul from the US, DrSanjeev Chaubey from Shanghai and Dr Padma Srivastv and Dr Harsh Mahajan from India threw light upon the stem cell therapy and the possibility of incorporating the same in treating COVID-19 pateints.

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Discovered the physiological mechanisms underlying the most common pediatric Leukemia – Science Codex

Friday, April 24th, 2020

B-cell acute lymphoblastic leukemia (B-ALL) is characterized by the accumulation of abnormal immature B-cell precursors (BCP) in the bone marrow (BM) and is the most common pediatric cancer. Among the different subtypes known in B-ALL, the most common one is characterized by the presence of a higher number of chromosomes than in healthy cells and is called High hyperdiploid B-ALL (HyperD-ALL). This genetic abnormality is an initiating oncogenic event affiliated to childhood B-ALL, and it remains poorly characterized.

HyperD-ALL comprises 30% of pediatric B-ALL and usually has a favorable clinical outcome, with 90% of survival in patients with this hematologic cancer. Despite this, until date, there was very little knowledge on how hyperdiploidy occurs in HyperD-ALL, as an initiating oncogenic event in B-ALL and which secondary alterations are necessary for leukemic B-ALL cells accumulation in the bone marrow, impeding the growth of healthy cells and leading to the clinical leukemia complications.

A precise knowledge of the physiopathogenic mechanisms underlying HyperD- ALL was necessary because the morbidity/mortality associated with HyperD-ALL still represents a clinical challenge due to the high number of patients suffering from this type of B-ALL. For this reason, Oscar Molina, researcher of the Group of Stem Cells, Developmental Biology, and Immunotherapy of the Josep Carreras Leukaemia Research Institute, has led research on the mechanisms underlying HyperD-ALL, unveiling how and why it happens, published in Blood Journal this April 2020.

Molina and the co-authors of the study hypothesized that the origin of the pathogenic mechanisms associated with hyperdiploidy in B-ALL could be in the moment of the cell's division, known as mitosis, which is a highly orchestrated cellular process that controls the equal distribution of the genetic material, already duplicated and compacted in chromosomes, in two "newborn" cells.

"We knew already that HyperD-ALL arises in a BCP in utero. However, the causal molecular mechanisms of hyperdiploidy in BCPs remained elusive. As faithful chromosome segregation is essential for maintaining the genomic integrity of cells, and deficient chromosome segregation leads to aneuploidy and cancer, we wanted to observe and deepen on what is happening in chromosomes' segregation in HyperD-ALL, because we suspected that by studying cell division in these cells we would find an explanation to this oncogenic process."

Molina was right. Researchers used a large cohort of primary pediatric B-ALL samples, 54. What Molina and his colleagues discovered was that three key processes and actors for correct mitosis or cell division and chromosome segregation were misfunctioning in hyperdiploid cells; that artificial disruption of these processes in blood cells with normal chromosome numbers generated hyperdiploid cells resembling those in B-ALL samples. Therefore, shedding light on the cellular and molecular mechanisms involved in HyperD-ALL origin and progression.

The main proteins and processes leading to fatal error were a malfunctioning of the Condensin complex, a multiprotein complex responsible for helping condense the genetic material correctly into chromosomes; the protein Aurora B kinase, that is responsible for a correct chromosome attachment to the spindle poles, thus ensuring proper chromosome segregation; and the mitotic checkpoint, or Spindle Assembly Checkpoint (SAC), the cell machinery involved in controlling that chromosomes are correctly separated to each pole of the cell that is dividing.

With these findings, Molina et al. have unveiled the molecular mechanisms that are altered in this frequent type of pediatric blood cancer.

"Next steps would be to study whether other subtypes of B-ALL with abnormal chromosome numbers, such as hypodiploid B-ALL, a very aggressive subtype of pediatric blood cancer characterized by lower numbers of chromosomes, share a common molecular mechanism. These studies will allow generating the first in vivo models of leukemias with abnormal chromosome numbers in mice that will be crucial to understand its origin and development, thus facilitating the development of more targeted and less toxic therapies for these pediatric blood cancers" stated Oscar Molina.

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Discovered the physiological mechanisms underlying the most common pediatric Leukemia - Science Codex

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A rampage through the body – Science Magazine

Friday, April 24th, 2020

The lungs are ground zero, but COVID-19 also tears through organ systems from brain to blood vessels.

Science's COVID-19 coverage is supported by the Pulitzer Center.

The coronavirus wreaked extensive damage (yellow) on the lungs of a 59-year-old man who died at George Washington University Hospital, as seen in a 3D model based on computed tomography scans.

On rounds in a 20-bed intensive care unit one recent day, physician Joshua Denson assessed two patients with seizures, many with respiratory failure, and others whose kidneys were on a dangerous downhill slide. Days earlier, his rounds had been interrupted as his team tried, and failed, to resuscitate a young woman whose heart had stopped. All of the patients shared one thing, says Denson, a pulmonary and critical care physician at the Tulane University School of Medicine. They are all COVID positive.

As the number of confirmed cases of COVID-19 approaches 2.5 million globally and deaths surpass 166,000, clinicians and pathologists are struggling to understand the damage wrought by the coronavirus as it tears through the body. They are realizing that although the lungs are ground zero, the virus' reach can extend to many organs including the heart and blood vessels, kidneys, gut, and brain.

[The disease] can attack almost anything in the body with devastating consequences, says cardiologist Harlan Krumholz of Yale University and Yale-New Haven Hospital, who is leading multiple efforts to gather clinical data on COVID-19. Its ferocity is breathtaking and humbling.

Understanding the rampage could help doctors on the front lines treat the roughly 5% of infected people who become desperately and sometimes mysteriously ill. Does a dangerous, newly observed tendency to blood clotting transform some mild cases into life-threatening emergencies? Is an overzealous immune response behind the worst cases, suggesting treatment with immune-suppressing drugs could help? And what explains the startlingly low blood oxygen that some physicians are reporting in patients who nonetheless are not gasping for breath? Taking a systems approach may be beneficial as we start thinking about therapies, says Nilam Mangalmurti, a pulmonary intensivist at the Hospital of the University of Pennsylvania (HUP).

What follows is a snapshot of the fast-evolving understanding of how the virus attacks cells around the body. Despite the more than 1500 papers now spilling into journals and onto preprint servers every week, a clear picture is elusive, as the virus acts like no pathogen humanity has ever seen. Without larger, controlled studies that are only now being launched, scientists must pull information from small studies and case reports, often published at warp speed and not yet peer reviewed. We need to keep a very open mind as this phenomenon goes forward, says Nancy Reau, a liver transplant physician who has been treating COVID-19 patients at Rush University Medical Center. We are still learning.

WHEN AN INFECTED PERSON expels virus-laden droplets and someone else inhales them, the novel coronavirus, called SARS-CoV-2, enters the nose and throat. It finds a welcome home in the lining of the nose, according to a recent arXiv preprint, because cells there are rich in a cell-surface receptor called angiotensin-converting enzyme 2 (ACE2). Throughout the body, the presence of ACE2, which normally helps regulate blood pressure, marks tissues potentially vulnerable to infection, because the virus requires that receptor to enter a cell. Once inside, the virus hijacks the cell's machinery, making myriad copies of itself and invading new cells.

As the virus multiplies, an infected person may shed copious amounts of it, especially during the first week or so. Symptoms may be absent at this point. Or the virus' new victim may develop a fever, dry cough, sore throat, loss of smell and taste, or head and body aches.

If the immune system doesn't beat back SARS-CoV-2 during this initial phase, the virus then marches down the windpipe to attack the lungs, where it can turn deadly. The thinner, distant branches of the lung's respiratory tree end in tiny air sacs called alveoli, each lined by a single layer of cells that are also rich in ACE2 receptors.

Normally, oxygen crosses the alveoli into the capillaries, tiny blood vessels that lie beside the air sacs; the oxygen is then carried to the rest of the body. But as the immune system wars with the invader, the battle itself disrupts healthy oxygen transfer. Frontline white blood cells release inflammatory molecules called chemokines, which in turn summon more immune cells that target and kill virus-infected cells, leaving a stew of fluid and dead cellspusbehind (see graphic, below). This is the underlying pathology of pneumonia, with its corresponding symptoms: coughing; fever; and rapid, shallow respiration. Some COVID-19 patients recover, sometimes with no more support than oxygen breathed in through nasal prongs.

But others deteriorate, often suddenly, developing a condition called acute respiratory distress syndrome. Oxygen levels in their blood plummet, and they struggle ever harder to breathe. On x-rays and computed tomography scans, their lungs are riddled with white opacities where black spaceairshould be. Commonly, these patients end up on ventilators. Many die, and survivors may face long-term complications (see sidebar, p. 359). Autopsies show their alveoli became stuffed with fluid, white blood cells, mucus, and the detritus of destroyed lung cells.

Some clinicians suspect the driving force in many gravely ill patients' downhill trajectories is a disastrous overreaction of the immune system known as a cytokine storm, which other viral infections are known to trigger. Cytokines are chemical signaling molecules that guide a healthy immune response; but in a cytokine storm, levels of certain cytokines soar far beyond what's needed, and immune cells start to attack healthy tissues. Blood vessels leak, blood pressure drops, clots form, and catastrophic organ failure can ensue.

Some studies have shown elevated levels of these inflammation-inducing cytokines in the blood of hospitalized COVID-19 patients. The real morbidity and mortality of this disease is probably driven by this out of proportion inflammatory response to the virus, says Jamie Garfield, a pulmonologist who cares for COVID-19 patients at Temple University Hospital.

But others aren't convinced. There seems to have been a quick move to associate COVID-19 with these hyperinflammatory states. I haven't really seen convincing data that that is the case, says Joseph Levitt, a pulmonary critical care physician at the Stanford University School of Medicine.

He's also worried that efforts to dampen a cytokine response could backfire. Several drugs targeting specific cytokines are in clinical trials in COVID-19 patients. But Levitt fears those drugs may suppress the immune response that the body needs to fight off the virus. There's a real risk that we allow more viral replication, Levitt says.

Meanwhile, other scientists are zeroing in on an entirely different organ system that they say is driving some patients' rapid deterioration: the heart and blood vessels.

IN BRESCIA, ITALY, a 53-year-old woman walked into the emergency room of her local hospital with all the classic symptoms of a heart attack, including telltale signs in her electrocardiogram and high levels of a blood marker suggesting damaged cardiac muscles. Further tests showed cardiac swelling and scarring, and a left ventriclenormally the powerhouse chamber of the heartso weak that it could only pump one-third its normal amount of blood. But when doctors injected dye in her coronary arteries, looking for the blockage that signifies a heart attack, they found none. Another test revealed the real cause: COVID-19.

How the virus attacks the heart and blood vessels is a mystery, but dozens of preprints and papers attest that such damage is common. A 25 March paper in JAMA Cardiology found heart damage in nearly 20% of patients out of 416 hospitalized for COVID-19 in Wuhan, China. In another Wuhan study, 44% of 36 patients admitted to the intensive care unit (ICU) had arrhythmias.

The disruption seems to extend to the blood itself. Among 184 COVID-19 patients in a Dutch ICU, 38% had blood that clotted abnormally, and almost one-third already had clots, according to a 10 April paper in Thrombosis Research. Blood clots can break apart and land in the lungs, blocking vital arteriesa condition known as pulmonary embolism, which has reportedly killed COVID-19 patients. Clots from arteries can also lodge in the brain, causing stroke. Many patients have dramatically high levels of D-dimer, a byproduct of blood clots, says Behnood Bikdeli, a cardiovascular medicine fellow at Columbia University Medical Center.

The more we look, the more likely it becomes that blood clots are a major player in the disease severity and mortality from COVID-19, Bikdeli says.

Infection may also lead to blood vessel constriction. Reports are emerging of ischemia in the fingers and toesa reduction in blood flow that can lead to swollen, painful digits and tissue death.

In the lungs, blood vessel constriction might help explain anecdotal reports of a perplexing phenomenon seen in pneumonia caused by COVID-19: Some patients have extremely low blood-oxygen levels and yet are not gasping for breath. In this scenario, oxygen uptake is impeded by constricted blood vessels rather than by clogged alveoli. One theory is that the virus affects the vascular biology and that's why we see these really low oxygen levels, Levitt says.

If COVID-19 targets blood vessels, that could also help explain why patients with pre-existing damage to those vessels, for example from diabetes and high blood pressure, face higher risk of serious disease. Recent Centers for Disease Control and Prevention (CDC) data on hospitalized patients in 14 U.S. states found that about one-third had chronic lung diseasebut nearly as many had diabetes, and fully half had pre-existing high blood pressure.

Mangalmurti says she has been shocked by the fact that we don't have a huge number of asthmatics or patients with other respiratory diseases in her hospital's ICU. It's very striking to us that risk factors seem to be vascular: diabetes, obesity, age, hypertension.

Scientists are struggling to understand exactly what causes the cardiovascular damage. The virus may directly attack the lining of the heart and blood vessels, which, like the nose and alveoli, are rich in ACE2 receptors. By altering the delicate balance of hormones that help regulate blood pressure, the virus might constrict blood vessels going to the lungs. Another possibility is that lack of oxygen, due to the chaos in the lungs, damages blood vessels. Or a cytokine storm could ravage the heart as it does other organs.

We're still at the beginning, Krumholz says. We really don't understand who is vulnerable, why some people are affected so severely, why it comes on so rapidly and why it is so hard [for some] to recover.

THE WORLDWIDE FEARS of ventilator shortages for failing lungs have received plenty of attention. Not so a scramble for another type of equipment: kidney dialysis machines. If these folks are not dying of lung failure, they're dying of renal failure, says neurologist Jennifer Frontera of New York University's Langone Medical Center, which has treated thousands of COVID-19 patients. Her hospital is developing a dialysis protocol with a different kind of machine to support more patients. What she and her colleagues are seeing suggests the virus may target the kidneys, which are abundantly endowed with ACE2 receptors.

According to one preprint, 27% of 85 hospitalized patients in Wuhan had kidney failure. Another preprint reported that 59% of nearly 200 hospitalized COVID-19 patients in China's Hubei and Sichuan provinces had protein in their urine, and 44% had blood; both suggest kidney damage. Those with acute kidney injury were more than five times as likely to die as COVID-19 patients without it, that preprint reported.

The lung is the primary battle zone. But a fraction of the virus possibly attacks the kidney. And as on the real battlefield, if two places are being attacked at the same time, each place gets worse, says co-author Hongbo Jia, a neuroscientist at the Chinese Academy of Sciences's Suzhou Institute of Biomedical Engineering and Technology.

One study identified viral particles in electron micrographs of kidneys from autopsies, suggesting a direct viral attack. But kidney injury may also be collateral damage. Ventilators boost the risk of kidney damage, as do antiviral compounds including remdesivir, which is being deployed experimentally in COVID-19 patients. Cytokine storms can also dramatically reduce blood flow to the kidney, causing often-fatal damage. And pre-existing diseases like diabetes can increase the chances of kidney injury. There is a whole bucket of people who already have some chronic kidney disease who are at higher risk for acute kidney injury, says Suzanne Watnick, chief medical officer at Northwest Kidney Centers.

ANOTHER STRIKING SET of symptoms in COVID-19 patients centers on the brain and nervous system. Frontera says 5% to 10% of coronavirus patients at her hospital have neurological symptoms. But she says that is probably a gross underestimate of the number whose brains are struggling, especially because many are sedated and on ventilators.

Frontera has seen patients with the brain inflammation encephalitis, seizures, and a sympathetic storm, a hyperreaction of the sympathetic nervous system that causes seizurelike symptoms and is most common after a traumatic brain injury. Some people with COVID-19 briefly lose consciousness. Others have strokes. Many report losing their sense of smell and taste. And Frontera and others wonder whether, in some cases, infection depresses the brain stem reflex that senses oxygen starvationanother explanation for anecdotal observations that some patients aren't gasping for air, despite dangerously low blood oxygen levels.

ACE2 receptors are present in the neural cortex and brain stem, says Robert Stevens, an intensive care physician at Johns Hopkins Medicine. And the coronavirus behind the 2003 severe acute respiratory syndrome (SARS) epidemica close cousin of today's culpritwas able to infiltrate neurons and sometimes caused encephalitis. On 3 April, a case study in the International Journal of Infectious Diseases, from a team in Japan, reported traces of new coronavirus in the cerebrospinal fluid of a COVID-19 patient who developed meningitis and encephalitis, suggesting it, too, can penetrate the central nervous system.

But other factors could be damaging the brain. For example, a cytokine storm could cause brain swelling. The blood's exaggerated tendency to clot could trigger strokes. The challenge now is to shift from conjecture to confidence, at a time when staff are focused on saving lives, and even neurologic assessments like inducing the gag reflex or transporting patients for brain scans risk spreading the virus.

Last month, Sherry Chou, a neurologist at the University of Pittsburgh Medical Center, began to organize a worldwide consortium that now includes 50 centers to draw neurological data from care patients already receive. Early goals are simple: Identify the prevalence of neurologic complications in hospitalized patients and document how they fare. Longer term, Chou and her colleagues hope to gather scans and data from lab tests to better understand the virus' impact on the nervous system, including the brain.

No one knows when or how the virus might penetrate the brain. But Chou speculates about a possible invasion route: through the nose, then upward and through the olfactory bulbexplaining reports of a loss of smellwhich connects to the brain. It's a nice sounding theory, she says. We really have to go and prove that.

A 58-year-old woman with COVID-19 developed encephalitis, with tissue damage in the brain (arrows).

Most neurological symptoms are reported from colleague to colleague by word of mouth, Chou adds. I don't think anybody, and certainly not me, can say we're experts.

IN EARLY MARCH, a 71-year-old Michigan woman returned from a Nile River cruise with bloody diarrhea, vomiting, and abdominal pain. Initially doctors suspected she had a common stomach bug, such as Salmonella. But after she developed a cough, doctors took a nasal swab and found her positive for the novel coronavirus. A stool sample positive for viral RNA, as well as signs of colon injury seen in an endoscopy, pointed to a gastrointestinal (GI) infection with the coronavirus, according to a paper posted online in The American Journal of Gastroenterology (AJG).

Her case adds to a growing body of evidence suggesting the new coronavirus, like its cousin SARS, can infect the lining of the lower digestive tract, where ACE2 receptors are abundant. Viral RNA has been found in as many as 53% of sampled patients' stool samples. And in a paper in press at Gastroenterology, a Chinese team reported finding the virus' protein shell in gastric, duodenal, and rectal cells in biopsies from a COVID-19 patient. I think it probably does replicate in the gastrointestinal tract, says Mary Estes, a virologist at Baylor College of Medicine.

Recent reports suggest up to half of patients, averaging about 20% across studies, experience diarrhea, says Brennan Spiegel of Cedars-Sinai Medical Center in Los Angeles, coeditor-in-chief of AJG. GI symptoms aren't on CDC's list of COVID-19 symptoms, which could cause some COVID-19 cases to go undetected, Spiegel and others say. If you mainly have fever and diarrhea, you won't be tested for COVID, says Douglas Corley of Kaiser Permanente, Northern California, co-editor of Gastroenterology.

The presence of virus in the GI tract raises the unsettling possibility that it could be passed on through feces. But it's not yet clear whether stool contains intact, infectious virus, or only RNA and proteins. To date, We have no evidence that fecal transmission is important, says coronavirus expert Stanley Perlman of the University of Iowa. CDC says that, based on experiences with SARS and with the coronavirus that causes Middle East respiratory syndrome, the risk from fecal transmission is probably low.

The intestines are not the end of the disease's march through the body. For example, up to one-third of hospitalized patients develop conjunctivitispink, watery eyesalthough it's not clear that the virus directly invades the eye.

Other reports suggest liver damage: More than half of COVID-19 patients hospitalized in two Chinese centers had elevated levels of enzymes indicating injury to the liver or bile ducts. But several experts told Science that direct viral invasion isn't likely the culprit. They say other events in a failing body, like drugs or an immune system in overdrive, are more likely causes of the liver damage.

This map of the devastation that COVID-19 can inflict on the body is still just a sketch. It will take years of painstaking research to sharpen the picture of its reach, and the cascade of effects in the body's complex and interconnected systems that it might set in motion. As science races ahead, from probing tissues under microscopes to testing drugs on patients, the hope is for treatments more wily than the virus that has stopped the world in its tracks.

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A rampage through the body - Science Magazine

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NHS’s oldest IVF clinic at risk of closure amid increasing privatisations – The Guardian

Friday, April 24th, 2020

The UKs oldest NHS fertility clinic is at risk of closure and another has been put out to private tender, as IVF provision is increasingly privatised and rationed.

Hospital bosses want to close the internationally renowned department of reproductive medicine at St Marys hospital, Manchester, saying they cannot afford to fund a 10m upgrade of the unit, the Guardian has learned.

In Leeds, the entire NHS provision of fertility and other gynaecology services was put out to tender earlier this year, with private clinics invited to bid for a 10-year contract estimated at 70m to provide reproductive care.

Two years ago North Bristol NHS trust sold off its IVF clinic to a private provider, saying it was no longer feasible because of a reduction in NHS-funded patients.

In England, the proportion of fertility treatment funded by the NHS dropped from 39% in 2012 to 35% in 2017, according to figures published last year by the regulator, the Human Fertilisation and Embryology Authority (HFEA). This is at odds with the rest of the UK, where public funding has remained stable or increased.

When it opened in 1982, four years after the first test tube baby, Louise Brown, was born in nearby Oldham, St Marys was the UKs first fully NHS funded IVF unit. It now performs over 2,000 fertility treatments every year, including around 1,200 IVF cycles, and offers highly specialised fertility preservation for cancer patients. It is also a top research centre, which led on the use of ovarian reserve tests to guide ovarian stimulation, the development of stem cell lines from human embryos, and the effects of IVF on baby birth weights.

The Manchester University NHS foundation trust (MFT) said no decisions had been made over the units future. But staff were briefed last month that the HFEA and local clinical commissioning groups (CCGs) had been told that all licensed treatment and research on the site may end by April 2021 if an alternative solution cannot be found.

MFT, which runs the hospital, is also exploring options including redeploying services and some of its 107 staff including many highly specialised roles but confirmed to staff that closure was a possibility.

The Guardian spoke to 10 members of staff at St Marys aware of the mooted closure. One said they understood the matter to be settled: St Marys have taken a proposal to the MFT group board to discontinue the IVF service and the group board have said, Yes, OK. How they discontinue it is what they need to decide next, they said.

If the change goes ahead, CCGs, which fund fertility treatment, will have to pay private clinics to carry out IVF and other fertility services. But staff at St Marys warn that the private sector will not be able to carry out some of the most specialised services currently offered by the NHS.

We offer highly specialised procedures in the NHS which private providers wont touch because they dont make money and are too difficult. For example, we aim to see women diagnosed with cancer within a week who want to freeze their eggs before they start chemotherapy. Many of these women are already very poorly and need really high quality anaesthetic care during egg collection, and that is just not available in the private sector because of the medical complications, said one source.

They added: Private clinics are also unlikely to help patients with kidney problems or heart problems. But when they come to us, we can address these issues before they begin IVF: a huge advantage of being part of a multi-disciplinary NHS Trust. Those patients will be disadvantaged if this happens.

They also expressed concerns about screening procedures in the private sector. In the NHS, anyone applying for fertility treatment undergoes a series of stringent checks, including an assessment of the welfare of the child: Our checks and ethics advisory committee often flag issues including prison sentences, a serious history of domestic violence, even people on the sex offender register. At private clinics they dont do anything like the same background checks.

A number of separate proposals were put to MFT to try to save some or all of the clinic, including turning the service into a social enterprise and forming a partnership with a private provider, as is being proposed in Leeds.

The deadline to apply to run the Leeds service was 23 March, the day the government announced the coronavirus lockdown in the UK. Shortly afterwards, clinics stopped all new treatments and the HFEA ordered private and NHS clinics to stop treating patients in the middle of an IVF cycle by 15 April.

A spokesperson for the MFT, which runs St Marys hospital, said no decision had been taken to shut the clinic permanently.

They said: Services provided by the department of reproductive medicine at St Marys hospital are regularly reviewed as part of a usual cycle to ensure that we continue to provide the best possible care and treatments for all our service users. No decisions have been made, therefore it would be inappropriate to provide any further detail before the outcome of any review has been finalised.

The HFEA said it could not disclose informal discussions between clinics and inspectors.

Many St Marys staff are worried not just about their patients and their jobs, but the logistics of closing down the clinic. Moving thousands of sperm samples and embryos held in freezers, for use in both treatment and research, was a mind-boggling challenge, said one.

One staff member said: Although possible relocation was mentioned, the fact that no viable alternative has been identified and that the cost was described as being too high left us thinking that this is not being explored and that closing the unit is the direction of travel. We are worried for our jobs but our biggest concern is for our patients, particularly those with the most complex needs who cannot be served elsewhere without high costs.

IVF provision has been put under pressure, nationally, by NHS funding cuts over the past decade leading to a postcode lottery of provision. Now only a minority of English CCGs offer the recommended three funded IVF cycles, with some refusing to fund any NHS fertility treatment at all.

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Vir Biotechnology (VIR): Stock on the Move – Investor Welcome

Thursday, April 23rd, 2020

Volatility in Focus:

The stock unfolded volatility at 6.97% during a week and it has been swapped around 11.65% over a month. Volatility is a rate at which the price of a security increases or decreases for a given set of returns. Volatility is measured by calculating the standard deviation of the annualized returns over a given period of time. It shows the range to which the price of a security may increase or decrease. Volatility measures the risk of a security. It is used in option pricing formula to gauge the fluctuations in the returns of the underlying assets. Volatility indicates the pricing behavior of the security and helps estimate the fluctuations that may happen in a short period of time. If the prices of a security fluctuate rapidly in a short time span, it is termed to have high volatility. If the prices of a security fluctuate slowly in a longer time span, it is termed to have low volatility.

The average true range is a volatility indicator. This stocks Average True Range (ATR) is currently standing at 4.39.

Vir Biotechnology (VIR) stock Trading Summary:

Vir Biotechnology (VIR) stock changed position at -1.54% to closing price of $30.08 in recent trading session. The last closing price represents the price at which the last trade occurred. The last price is also the price on which most charts are based; the chart updates with each change of the last price. The stock registered Wednesday volume of 944495 shares. Daily volume is the number of shares that are traded during one trading day. High volume is an indication that a stock is actively traded, and low volume is an indication that a stock is less actively traded. Some stocks tend always to have high volume, as they are popular among day traders and investors alike. Other stocks tend always to have low volume, and arent of particular interest to short-term traders. The stock average trading capacity stands with 1.11M shares and relative volume is now at 0.85.

Vir Biotechnology (VIR):

If you are considering getting into the day trading or penny stock market, its a legitimate and profitable method for making a living. Every good investor knows that in order to make money on any investment, you must first understand all aspects of it, so lets look at daily change, stock price movement in some particular time frame, volatility update, performance indicators and technical analysis and analyst rating. Picking a stock is very difficult job. There are many factors to consider before choosing a right stock to invest in it. If picking stock was easy, everyone would be rich right? This piece of financial article provides a short snap of Vir Biotechnology (VIR) regarding latest trading session and presents some other indicators that can help you to support yours research about Vir Biotechnology (VIR).

Vir Biotechnology (VIR) Stock Price Movement in past 50 Days period and 52-Week period

Vir Biotechnology (VIR) stock demonstrated 158.19% move opposition to 12-month low and unveiled a move of -59.89% versus to 12-month high. The recent trading activity has given its price a change of -59.89% to its 50 Day High and 86.95% move versus to its 50 Day Low. Prices of commodities, securities and stocks fluctuate frequently, recording highest and lowest figures at different points of time in the market. A figure recorded as the highest/lowest price of the security, bond or stock over the period of past 52 weeks is generally referred to as its 52-week high/ low. It is an important parameter for investors (as they compare the current trading price of the stocks and bonds to the highest/lowest prices they have reached in the past 52 weeks) in making investment decisions. It also plays an important role in determination of the predicted future prices of the stock.

Vir Biotechnology (VIR) Stock Past Performance

Vir Biotechnology (VIR) stock revealed -17.84% return for the recent month and disclosed 81.86% return in 3-month period. The stock grabbed 108.74% return over last 6-months. To measure stock performance since start of the year, it resulted a change of 139.20%. Past performance shows you the funds track record, but do remember that past performance is not an indication of future performance. Read the historical performance of the stock critically and make sure to take into account both long- and short-term performance. Past performance is just one piece of the puzzle when evaluating investments. Understanding how performance fits in with your overall investing strategy and what else should be considered can keep you from developing tunnel vision.

Overbought and Oversold levels

The stock has RSI reading of 49.6. RSI gives an indication of the impending reversals or reaction in price of a security. RSI moves in the range of 0 and 100. So an RSI of 0 means that the stock price has fallen in all of the 14 trading days. Similarly, an RSI of 100 means that the stock price has risen in all of the 14 trading days. In technical analysis, an RSI of above 70 is considered an overbought area while an RSI of less than 30 is considered as an oversold area. RSI can be used as a leading indicator as it normally tops and bottoms ahead of the market, thereby indicating an imminent correction in the price of a security. It is pertinent to note that the levels of 70 and 30 needs to be adjusted according to the inherent volatility of the security in question.

Analyst Watch: Analysts have assigned their consensus opinion on this stock with rating of 3.2 on scale of 1 to 5. 1 or 2 =>Buy view 4 or 5 => Sell opinion. 3 =>Hold. Analysts recommendations are the fountainhead of equity research reports and should be used in tangent with proprietary research and investment methodologies in order to make investment decisions.

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Nanoparticles in Biotechnology and Pharmaceuticals Market Overview by 2026: Verified Market Research – Cole of Duty

Thursday, April 23rd, 2020

Shire

Global Nanoparticles in Biotechnology and Pharmaceuticals Market Segmentation

This market was divided into types, applications and regions. The growth of each segment provides an accurate calculation and forecast of sales by type and application in terms of volume and value for the period between 2020 and 2026. This analysis can help you develop your business by targeting niche markets. Market share data are available at global and regional levels. The regions covered by the report are North America, Europe, the Asia-Pacific region, the Middle East, and Africa and Latin America. Research analysts understand the competitive forces and provide competitive analysis for each competitor separately.

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The report provides an in-depth assessment of growth and other aspects of the market in key countries such as the United States, Canada, Mexico, Germany, France, the United Kingdom, Russia and the United States Italy, China, Japan, South Korea, India, Australia, Brazil and Saudi Arabia. The chapter on the competitive landscape of the global market report contains important information on market participants such as business overview, total sales (financial data), market potential, global presence, Nanoparticles in Biotechnology and Pharmaceuticals sales and earnings, market share, prices, production locations and facilities, products offered and applied strategies. This study provides Nanoparticles in Biotechnology and Pharmaceuticals sales, revenue, and market share for each player covered in this report for a period between 2016 and 2020.

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Nanoparticles in Biotechnology and Pharmaceuticals Market Size by Manufacturer: Here, the report concentrates on revenue and production shares of manufacturers for all the years of the forecast period. It also focuses on price by manufacturer and expansion plans and mergers and acquisitions of companies.

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Tags: Nanoparticles in Biotechnology and Pharmaceuticals Market Size, Nanoparticles in Biotechnology and Pharmaceuticals Market Trends, Nanoparticles in Biotechnology and Pharmaceuticals Market Forecast, Nanoparticles in Biotechnology and Pharmaceuticals Market Growth, Nanoparticles in Biotechnology and Pharmaceuticals Market Analysis

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Nanoparticles in Biotechnology and Pharmaceuticals Market Overview by 2026: Verified Market Research - Cole of Duty

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Arch Oncology Appoints Biotechnology Industry Veteran Julie Hambleton, M.D. to Board of Directors – Yahoo Finance

Thursday, April 23rd, 2020

Arch Oncology, Inc., a clinical-stage immuno-oncology company focused on the discovery and development of best-in-class anti-CD47 antibody therapies, today announced the appointment of Julie Hambleton, M.D. to the Companys Board of Directors.

"Julie is an accomplished biotechnology executive who brings extensive oncology clinical drug development expertise to our Board of Directors," said Julie M. Cherrington, Ph.D., President and Chief Executive Officer of Arch Oncology. "As we continue to advance AO-176 in clinical development for select solid tumors and plan for additional indications in hematologic malignancies including multiple myeloma, I am thrilled to have Julie join the Board of Directors. We share a deep commitment to developing novel therapies for patients with cancer and I look forward to working with her."

Julie Hambleton, M.D., Chief Medical Officer at IDEAYA Biosciences and Director for Arch Oncology, added, "I am very encouraged by the growing body of preclinical data, the clinical progress, and future clinical potential of AO-176. This novel anti-CD47 antibody has a best-in-class profile and I look forward to sharing my insights gained over 20 years in drug development to guide ongoing and future potential opportunities for AO-176 in across various oncology indications."

Julie Hambleton, M.D. is a senior biotechnology executive with over 20 years of experience in clinical drug development from pre-clinical through Phase 4 and post-marketing studies. She has extensive experience working with regulatory agencies, including the U.S. FDA and the European Medicines Agency (EMA), and in filings of Investigational New Drug Applications (INDs), Biologics License Applications (BLAs), and Special Protocol Assessments (SPAs). Dr. Hambleton serves as Chief Medical Officer of IDEAYA Biosciences. Previously, she was Vice President, Head of U.S. Medical at Bristol-Myers Squibb, overseeing Medical & Health Economic and Outcomes Research activities in support of the Oncology, Immuno-Oncology, Specialty and Cardiovascular marketed portfolios. Previously, she served as Executive Vice President and Chief Medical Officer at Five Prime Therapeutics and Vice President, Clinical Development, at Clovis Oncology. Dr. Hambleton began her industry career at Genentech, most recently as Group Medical Director,Global Clinical Development, leading a cross-functional group conducting Phase 2 and 3 trials of Avastin.

Dr. Hambleton completed her medical and hematology-oncology training at the University California, San Francisco, where she then served on faculty from 1993 to 2003. She received a B.S. from Duke University, and M.D. from Case Western Reserve University School of Medicine and was Board-certified in Hematology and Internal Medicine.

In addition, Dr. Hambleton serves as a Director on IGM Biosciences Board of Directors.

About Arch Oncology

Arch Oncology, Inc. is a privately-held, clinical-stage immuno-oncology company focused on the discovery and development of best-in-class antibody therapies for the treatment of patients with select solid tumors and hematologic malignancies, including multiple myeloma. The Companys next-generation anti-CD47 antibodies are highly differentiated, with the potential to improve upon the safety and efficacy profile relative to other agents in this class. Arch Oncologys lead product candidate AO-176 is in a Phase 1 clinical trial for the treatment of patients with select solid tumors. In addition, the Company is advancing a number of antibody pipeline programs for the treatment cancer. For more information please visit http://www.archoncology.com.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200421005212/en/

Contacts

Amy Figueroa, CFAFor Arch Oncologyafigueroa@archoncology.com 650-823-2704

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Arch Oncology Appoints Biotechnology Industry Veteran Julie Hambleton, M.D. to Board of Directors - Yahoo Finance

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Biotechnology Industry: Does Cara Therapeutics Inc (CARA) Stock Beat its Rivals? – InvestorsObserver

Thursday, April 23rd, 2020

The 75 rating InvestorsObserver gives to Cara Therapeutics Inc (CARA) stock puts it near the top of the Biotechnology industry. In addition to scoring higher than 87 percent of stocks in the Biotechnology industry, CARAs 75 overall rating means the stock scores better than 75 percent of all stocks.

Trying to find the best stocks can be a daunting task. There are a wide variety of ways to analyze stocks in order to determine which ones are performing the strongest. Investors Observer makes the entire process easier by using percentile rankings that allows you to easily find the stocks who have the strongest evaluations by analysts.

This ranking system incorporates numerous factors used by analysts to compare stocks in greater detail. This allows you to find the best stocks available in any industry with relative ease. These percentile-ranked scores using both fundamental and technical analysis give investors an easy way to view the attractiveness of specific stocks. Stocks with the highest scores have the best evaluations by analysts working on Wall Street.

Cara Therapeutics Inc (CARA) stock is trading at $15.81 as of 11:14 AM on Wednesday, Apr 22, a rise of $0.39, or 2.53% from the previous closing price of $15.42. The stock has traded between $15.29 and $16.44 so far today. Volume today is below average. So far 328,715 shares have traded compared to average volume of 541,813 shares.

To see InvestorsObserver's Sentiment Score for Cara Therapeutics Inc click here.

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Biotechnology Industry: Does Cara Therapeutics Inc (CARA) Stock Beat its Rivals? - InvestorsObserver

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Where Does Intercept Pharmaceuticals Inc (ICPT) Stock Fall in the Biotechnology Field? – InvestorsObserver

Thursday, April 23rd, 2020

Intercept Pharmaceuticals Inc (ICPT) is near the top in its industry group according to InvestorsObserver. ICPT gets an overall rating of 72. That means it scores higher than 72 percent of stocks. Intercept Pharmaceuticals Inc gets a 83 rank in the Biotechnology industry. Biotechnology is number 8 out of 148 industries.

Analyzing stocks can be hard. There are tons of numbers and ratios, and it can be hard to remember what they all mean and what counts as good for a given value. InvestorsObserver ranks stocks on eight different metrics. We percentile rank most of our scores to make it easy for investors to understand. A score of 72 means the stock is more attractive than 72 percent of stocks.

These rankings allows you to easily compare stocks and view what the strengths and weaknesses are of a given company. This lets you find the stocks with the best short and long term growth prospects in a matter of seconds. The combined score incorporates technical and fundamental analysis in order to give a comprehensive overview of a stocks performance. Investors who then want to focus on analysts rankings or valuations are able to see the separate scores for each section.

Intercept Pharmaceuticals Inc (ICPT) stock is trading at $81.86 as of 10:41 AM on Tuesday, Apr 21, a loss of -$0.75, or -0.91% from the previous closing price of $82.61. The stock has traded between $80.53 and $83.30 so far today. Volume today is less active than usual. So far 80,863 shares have traded compared to average volume of 667,682 shares.

To see InvestorsObserver's Sentiment Score for Intercept Pharmaceuticals Inc click here.

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Where Does Intercept Pharmaceuticals Inc (ICPT) Stock Fall in the Biotechnology Field? - InvestorsObserver

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Could genetics explain why some COVID-19 patients fare worse than others? – Live Science

Thursday, April 23rd, 2020

Certain genetic differences might separate people who fall severely ill with COVID-19 from those who contract the infection but hardly develop a cough, a new preliminary study suggests.

The research is still in its early days, though, experts say.

The immune system can react to viruses thanks, in part, to specific genes that help cells spot unfamiliar bugs when they enter the body. The genes, known as human leukocyte antigen (HLA) genes, contain instructions to build proteins that bind to bits of a pathogen; those proteins serve as warning flags to alert immune cells. The immune cells, once trained to recognize these bits, jumpstart the process of building antibodies to target and destroy the invasive germ.

Within each individual, HLA genes code for three different classes of proteins; in other words, HLAs come in a variety of flavors, and depending on which HLAs you have, your body may be better or worse equipped to fight off certain germs including SARS-CoV-2, the virus that causes COVID-19.

In a new study, published April 17 in the Journal of Virology, researchers used computer models to predict which combination of HLAs might be best at binding SARS-CoV-2, and which might be worst.

If certain HLAs can bind well to a large proportion of the virus's proteins, "we expect there to be a more protective immune response," authors Abhinav Nellore and Dr. Reid Thompson, who lead a computational biology research group at the Oregon Health and Science University, told Live Science in an email. A better bind means that the viral proteins are more likely to be presented to immune cells and prompt the production of specific antibodies, the authors said.

"If the interaction is not stable, you will not have a proper [immune] response," said Dr. Shokrollah Elahi, an associate professor in the Department of Dentistry and adjunct associate professor in the Department of Medical Microbiology and Immunology at the University of Alberta, who was not involved in the study.

Related: 10 deadly diseases that hopped across species

But a stable bond, alone, does not guarantee the best immune response, Elahi added. If an HLA binds a viral protein that happens to be critical for the germ to replicate and survive, the subsequent antibody activity will likely target the virus more effectively than that prompted by a less important protein, Elahi said.

"This is an issue we did not address in our analysis," the authors noted. Instead, the team focused on predicting how well different HLA types could bind to bits of SARS-CoV-2. Their analysis identified six HLA types with a high capacity to bind different SARS-CoV-2 protein sequences, and three with a low capacity to do so. Specifically, a HLA type known as HLA-B*46:01 had the lowest predicted capacity to bind to bits of SARS-CoV-2.

The same HLA type cropped up in a 2003 study published in the journal BMC Medical Genetics, which assessed patients infected with SARS-CoV, a closely related coronavirus that caused an outbreak of severe acute respiratory syndrome in the early 2000s. The study found that, in a group of patients of Asian descent, the presence of HLA-B*46:01 was associated with severe cases of the infection. In their paper, the research group noted that more clinical data would be needed to confirm the connection and the same goes for the new study of SARS-CoV-2, Nellore and Thompson said.

"The most substantial limitation of our study is that this was conducted entirely on a computer and did not involve clinical data from COVID-19 patients," the authors said. "Unless and until the findings we present here are clinically validated, they should not be employed for any clinical purposes," they added.

"In the body, we have so many things interacting," Elahi said. HLAs represent just one piece of a large, intricate puzzle that comprises the human immune system, he said. To better understand the variety of immune responses to COVID-19, Elahi and his research group aim to assess markers of immune system activity in infected patients and also catalog the ratio of immune cell types present in their bodies. While taking age, sex and other demographic factors into account, these so-called immunological profiles could help pinpoint when and why the illness takes a turn in some patients.

The clinical data could be assessed in parallel with genetic data gathered from the same patients, Elahi added. Similarly, Nellore and Thompson said that "COVID-19 testing should be paired with HLA typing, wherever [and] whenever possible," to help determine how different HLA types relate to symptom severity, if at all. Partnerships with genetic testing companies, biobanks and organ transplant registries could also offer opportunities to study HLA types in larger populations of people, they said.

"We cannot in good conscience predict at this point who will be more or less susceptible to the virus because we have not analyzed any clinical outcomes data with respect to HLA type to know that any of our predictions are valid," the authors said. If future studies support the notion that some HLA genes protect people from the virus, while others place patients at greater risk, those in the latter group could be first in line for vaccination, they added.

"In addition to prioritizing vaccinating the elderly or those with preexisting conditions, one could prioritize vaccinating people with HLA genotypes that suggest the SARS-CoV-2 virus is more likely to give them worse symptoms."

The authors went on to analyze how well HLAs can bind SARS-CoV-2 as compared with other coronaviruses, such as those that cause the common cold and infect humans often. They identified several viral bits shared between SARS-CoV-2 and at least one of these common viruses, suggesting exposure to one germ could somewhat protect the body against the other.

"If someone was previously exposed to a more common coronavirus and had the right HLA types ... then it is theoretically possible that they could also generate an earlier immune response against the novel SARS-CoV-2," the authors said. On the other hand, exposure to a similar virus could leave the body ill-equipped to fight off the new one, if, for instance, "the body is using an old set of tools that aren't ideally suited to address the new problem," the authors said.

Originally published on Live Science.

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Scientists use genetics to study how the world’s three narwhal populations are affected by climate shifts – The Narwhal

Thursday, April 23rd, 2020

If you want to learn about your ancestry, you can spit into a test-tube and retrieve your DNA results a month later online.

Scientists seeking to learn about the genetics of the narwhal had to use more elaborate methods to gather DNA samples of the deep-diving whale that lives in the ice-cold waters of the Arctic.

Hoping to unravel the demographic history of the narwhal, often called the unicorn of the sea, the scientists collected narwhal tissue samples from Inuit hunters in Canadas far north and Greenland, and tested narwhal remains from archeological digs in northern Europe and Russia.

They even got permission to take samples of narwhal tusks from the King of Denmarks throne chair, made from Norwegian narwhal tusks and guarded by three life-sized silver lions with manes of real gold.

They had special access to be able to drill little tiny bits of tusk from that throne, said Steven Ferguson, an Arctic marine mammal research scientist with Fisheries and Oceans Canada.

Ferguson is one of 15 co-authors of a study, published on April 21 by the Proceedings of the Royal Society B: Biological Sciences, that helps unwind a little bit more of the mystery and mystique surrounding the narwhal, a close relative of the beluga whale.

Until recently, little was known about the light-coloured cetacean most commonly recognized for its spiralled tusk a tooth extending through its upper lip. Only in 2017 did scientists discover the narwhal uses its tusk, a sensory device, to smack fish before swallowing them.

Using a combination of genetics and habitat modelling, Ferguson and other scientists investigated how past climatic shifts affected the distribution of the narwhal, one of the Arctic species most vulnerable to climate change.

They discovered low levels of genetic diversity among the worlds three narwhal populations, the two largest of which are found in Canada.

The scientists also found that habitat availability has been critical to the success of narwhals over the past tens of thousands of years, raising concerns about the fate of the migratory whale in a rapidly warming Arctic.

There are approximately 200,000 narwhals in the world.

Populations are named for where they summer. The vast majority of narwhals are found in Canada, in two groups known as the Baffin Bay and Hudsons Bay populations. A third population, numbering about 10,000 animals, is found in Greenland, extending to Svalbard an island between Norway and the North Pole and as far as Russia.

Its pretty remarkable that Canada has this resource but its also a lot of responsibility, said Ferguson, who worked with Inuit hunters to gather tissue samples for the study.

We are the ones who are going to have to manage and conserve this species going forward into the future.

DFO scientist Steve Ferguson in the field, conducting research on the worlds narwhal populations. Photo: Steve Ferguson

Narwhals appear only to have ever been an Atlantic species, and all three populations are closely related. Researchers found narwhals have one of the lowest genetic diversities of all marine mammals.

I still dont think weve quite solved that puzzle as to why it is so low, Ferguson said in an interview. Maybe there was some kind of bottleneck way back in the past. This history thats been explained by the genomic study here hasnt really found a good explanation for that.

The study found a long-term, low overall population size that increased when suitable habitat expanded following the last Ice Age. Like other polar marine predators, narwhal populations contracted into smaller areas during the last glaciation.

Its a bit of a mystery as to how fragmented they might have been, Ferguson said.

The study also looked into the future, forecasting what impact global warming might have on populations.

Researchers estimated a 25 per cent decline in habitat suitability by 2100, with a 1.6 degrees northward shift in habitat availability, suggesting narwhal habitat is likely to contract as sea temperatures rise and sea ice continues to melt.

The genetic ghost hunters

Ferguson said there will be a slight decrease in populations, including in the east Greenland group.

Narwhal distribution will be further affected in the near future by increased human encroachment, changes in prey availability, new competitors and increased predation by killer whales, according to the study.

More open water is good for narwhals to some extent, Ferguson said. But they will have competitors and disease and problems coming from the south [and] thats going to continue to push them further north.

Much depends on narwhals having access to the habitat they need to thrive, he said.

Baffin Bay seems to be a perfect spot for them right now, at least in winter. Theyre really deep diving animals, well adapted to diving to extreme depths, up to 2 kilometres. Baffin Bay allows them to do that and has some really good food.

All other Arctic marine mammals are circumpolar, meaning they are found around the world.

But narwhal are unique, Ferguson said. They really seem to have this Atlantic Ocean habitat. So theres an open question as to what might happen as we continue to lose sea ice.

The Arctic is warming at an unprecedented rate. A new study, published in Geophysical Research Letters, predicts summer Arctic sea ice will disappear before 2050, with devastating consequences for the Arctic ecosystem.

Narwhals most vulnerable to increased shipping in Arctic

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Scientists use genetics to study how the world's three narwhal populations are affected by climate shifts - The Narwhal

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Genetic variants linked with onset, progression of POAG – Ophthalmology Times

Thursday, April 23rd, 2020

Genetic variants that are unrelated to the IOP are associated with a family history of glaucoma and play a role in the onset of primary open-angle glaucoma (POAG). Genetic variants that are related to the IOP are associated with the age at which glaucoma is diagnosed and are associated with disease progression.

What is known about POAG, the most prevalent form of glaucoma, is that increased IOP and myopia are risk factors for damage to the optic nerve in POAG.

Related: Stent offers IOP stability more than three years after surgery

A family history of glaucoma is a major risk factor for development of POAG, in light of which, therefore, genetic factors are thought to be important in the disease pathogenesis and a few genes mutations have been identified as causing POAG, according to Fumihiko Mabuchi, MD, PhD, professor, Department of Ophthalmology, Faculty of Medicine, University of Yamanashi, Kofu, Japan.

Myopia has been shown to be a risk factor for POAG in several studies. However, it can be difficult to diagnose true POAG in myopic patients and controversy exists over whether it is real risk factor.

Myopic optic discs are notoriously difficult to assess, and myopic patients may have visual field defects unrelated to any glaucomatous process.

The prevalence of POAG increases with age, even after compensating for the association between age and IOP.

Related: Preservative-free tafluprost/timolol lowers IOP well, glaucoma study shows

Part of the storyDr. Mabuchi and his and colleagues, recounted that these factors are only part of the story.

According to Dr. Mabuchi and his colleagues, cases of POAG caused by these gene mutations account for several percent of all POAG cases, and most POAG is presumed to be a polygenic disease.

Recent genetic analyses, the investigators explained, have reported genetic variants that predispose patients to development of POAG and the additive effect of these variants on POAG, which are classified as two types.

The first genetics variants are associated with IOP elevation.

Related: Sustained-release implant offers long-term IOP control, preserved visual function

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Genetic variants linked with onset, progression of POAG - Ophthalmology Times

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The Better Half: On the Genetic Superiority of Women review bold study of chromosomal advantage – The Guardian

Thursday, April 23rd, 2020

It was noticeable from the initial outbreak in Wuhan that Covid-19 was killing more men than women. By February, data from China, which involved 44,672 confirmed cases of the respiratory disease, revealed the death rate for men was 2.8%, compared to 1.7% among women. For past respiratory epidemics, including Sars, Mers and the 1918 Spanish flu, men were also at significantly greater risk. But why?

Much of the reason for the Covid-19 disparity was put down to mens riskier behaviours around half of Chinese men are smokers, compared with just 3% of women, for instance. But as the coronavirus has spread globally, its proved deadlier to men everywhere that data exists (the UK and US notably and questionably do not collect sex-disaggregated data). Italy, for instance, has had a case fatality rate of 10.6% for men, versus 6% for women, whereas the sex disparity for smoking (now a known risk factor) is smaller there than China 28% of men and 19% of women smoke. In Spain, twice as many men as women have died. Smoking, then, is unlikely to account for all of the sex disparity in Covid-19 deaths.

Age and co-morbidity (pre-existing health conditions, including diabetes, cardiovascular disease or cancer) are the biggest risk factors, and that describes more older men than women. There may also be a sex difference in how people fight infection, due to immunological or hormonal differences oestrogen is shown to increase the antiviral response of immune cells.

If women are mounting a more effective immune response to Covid-19, it could be because many of the genes that regulate the immune system are encoded on the X chromosome. Everybody gets one X chromosome at conception from their mother. However, sex is determined (for the vast majority) by the chromosome received from their father: females get an additional X, whereas males do not (they receive a Y). According to The Better Half by American physician Sharon Moalem, having this second X chromosome gives women an immunological advantage. Every cell in a womans body has twice the number of X chromosomes as a mans, and so twice the number of genes that can be called upon to regulate her immune response, he says. Only one of the X chromosomes in each cell will be active at any time, but having that diversity of options gives women a better immunological toolbox to fight infections.

Moalem describes the possession of XX chromosomes as female genetic superiority. In the case of Covid-19, for instance, the virus uses its spike protein as a key to unlock a receptor protein on the outside of our human cells, called ACE-2, and gain entry. As the ACE-2 protein is on the X chromosome, men will have identical versions of ACE-2 on all their cells if the virus can unlock one, it can unlock all, he wrote recently in a Twitter thread. Women, though, have two different ACE-2 genes on their two X chromosomes, which may make it harder for the Covid-19 virus to break into all their cells, as it has to unlock two different proteins. Furthermore, once the ACE-2 is unlocked, it cannot perform its function, which, in the case of lung cells, is to clear fluid buildup during infection. So males, with all of their ACE-2 proteins affected, will suffer this more than females, he says. Moalem believes this may be the crucial advantage that XX-carrying women have over XY-carrying men in Covid-19 infection mortality.

Its an intriguing theory, and in his provocative book (written before the Covid-19 outbreak) Moalem expands the XX advantage to explain a whole range of life factors, from womens increased longevity to their lesser incidence of autism. It is incontrovertible that women are far less likely to suffer from X-linked genetic disorders, which include everything from Hunter syndrome to colour-blindness, because they usually have an unaffected X chromosome to fall back on. Indeed, in the case of colour vision, Moalem posits that having a second X chromosome can give some women a visual superpower, enabling them to see 100 times the usual colour range due to the extra diversity of receptors they carry on their multiple Xs.

It is striking that Moalem barely references environmental and social factors in a book about sex differences in health outcomes

However, the evidence for other of Moalems claims for the protective role of a second X chromosome, such as in autism spectrum disorders or behavioural traits, is less convincing. A broad range of genes play complex roles in the workings of the brain, and attributing a simple chromosomal relationship is brave. (It should be noted that Moalem authored the questionable The DNA Restart: Unlock Your Personal Genetic Code to Eat for Your Genes, Lose Weight, and Reverse Ageing in 2016.)

Outside of inherited genetic disorders, such as haemophilia, most conditions are attributable to a range of factors, including cultural norms, behaviours and social and environmental aspects as well as a host of biological factors. For Covid-19, for instance, gender-based norms around smoking and hand-washing, collective or individualistic mindsets that affect compliance with social-distance requests, how polluted your city is, whether you are a caregiver, and poverty and nutrition level all play a part in determining your infection risk and disease outcome. And, as weve seen, a range of co-morbidities increase risk are they too made more likely by absence of a second X chromosome? In many cases, such as cancers and lung disease, Moalem believes so a fascinating theory that surely deserves more study.

It is striking, though, that Moalem barely references environmental and social factors in a book about sex differences in health outcomes. This is particularly problematic when discussing sex differences in the brain, given the history of prejudicial research in this area. Much as this reviewer enjoys the rare pleasure of being described as the stronger, better, and superior sex certainly it is a change from being described as the weaker sex, as women have throughout history it is nevertheless an uncomfortable valuation. Claims for significant innate cognitive or behavioural advantages between the sexes have largely been debunked in the past few years by a range of influential books and research, and while there are differences, in most cases these are at least as great between individuals of each sex as between the sexes.

This is, however, a book that openly champions women, and it is most enjoyable when giving centre stage to female scientists, who have been too often overlooked. Moalems point is that, just as womens discoveries have been ignored, so too has the importance of their second X chromosome. Even today, medical and pharmaceutical research overwhelmingly favours male subjects, blinding us to knowledge that could lead to breakthroughs, and disadvantaging women who suffer inappropriate treatments and dosing. As men continue to fill the Covid-19 morgues faster than women, Moalem is on a quest to draw the worlds attention to a chromosomal tool we might just need.

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Is anxiety genetic? It’s a combination of genes and your environment – Insider – INSIDER

Thursday, April 23rd, 2020

Anxiety disorders are the most common type of mental illness. In a given year, 19% of Americans experience an anxiety disorder, according to the National Association on Mental Illness (NAMI).

Among the most common are:

Scientists have long debated the importance of nature versus nurture in terms of human development and illness. We now know that genetics play a significant role in the development of anxiety. Particularly, researchers have found that genes on chromosome 9 are associated with anxiety.

But your experiences within your environment including family upbringing and major life events are also important factors. Here's what you need to know about how genes and life experiences contribute to anxiety.

You're more likely to develop an anxiety disorder if another member of your family also has an anxiety disorder.

Research has indicated that anxiety disorders have a heritability rate of 26% for lifetime occurrence. This heritability rate means that 26% of the variability in whether or not people develop anxiety is caused by genetics.

So, about one-quarter of your risk for developing anxiety is genetic. That means other factors, such as traumatic experiences or physical illnesses, can have a larger impact. And your family can still contribute to anxiety in ways other than genetics.

"Family provides both the genes and the environment. It might be genes or it may be because a family member modeled a very anxious way of being in the world or often a combination of both," says Elena Touroni, PsyD, a psychologist and co-CEO at My Online Therapy. "It can be difficult to disentangle genes and environment."

One 2018 study found that children with anxiety disorders were three times more likely than children without disorders to have at least one parent with an anxiety disorder. The connection was particularly strong for social anxiety.

The study authors suggest that in addition to genetic risk, parents "model" behavior that increases the risk of their child developing social anxiety. For example, a parent who avoids social events might unintentionally teach their child to do the same.

However, adults who were raised by parents with anxiety can mitigate their risk of developing an anxiety disorder by learning how to manage anxiety with effective stress-management techniques. If you're a parent with anxiety, the earlier you teach your kid about this, the better.

"The best thing you can do is be aware of the fact that there is a higher chance that you might be prone to anxiety yourself," Touroni says. "Make a conscious effort to learn techniques to calm the mind, such as mindfulness. Also, having psychological therapy will help you better understand the anxieties of the people in your family, and therefore what they have left you vulnerable to as a result."

You don't need to have a family member with an anxiety disorder in order to develop anxiety. A stressful or traumatic event, for example, can increase the risk of developing an anxiety disorder.

"The main underlying core belief of any anxiety disorder is an exaggerated sense of vulnerability in the world of yourself or the people you care about," Touroni says. "Fundamentally, it's about understanding whether your experiences led you to develop a belief that the world is a dangerous place."

In particular, child sexual abuse and family violence may lead to an increased risk for anxiety. Moreover, having three or more adverse childhood experiences these are somewhat traumatic events for children, ranging from divorced parents to abuse is associated with a higher likelihood of developing anxiety.

Different childhood experiences at home, school and elsewhere can help explain why some family members might develop anxiety while others don't.

For example, a 2018 study followed 49,524 twins for 25 years. The researchers found that as twins aged and their environments became more different, the influence of heritability on their chance of developing anxiety decreased. In short: even though the twins shared genetics, their risk factors for anxiety were affected more by their environment than their genes.

In the end, there's no concrete set of factors that can predict if you will develop anxiety, or not.

"Mental illness is very different to physical illness. We can't always find a concrete link because there are a lot of variables," Touroni says. "Our mental wellbeing is influenced by so many different factors, and because of that, it's difficult to isolate genetic loading from environmental influence."

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Is anxiety genetic? It's a combination of genes and your environment - Insider - INSIDER

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Covid-19 Arrived in Seattle. Where It Went From There Stunned the Scientists. – The New York Times

Thursday, April 23rd, 2020

SEATTLE As the coronavirus outbreak consumed the city of Wuhan in China, new cases of the virus began to spread out like sparks flung from a fire.

Some landed thousands of miles away. By the middle of January, one had popped up in Chicago, another one near Phoenix. Two others came down in the Los Angeles area. Thanks to a little luck and a lot of containment, those flashes of the virus appear to have been snuffed out before they had a chance to take hold.

But on Jan. 15, at the international airport south of Seattle, a 35-year-old man returned from a visit to his family in the Wuhan region. He grabbed his luggage and booked a ride-share to his home north of the city.

The next day, as he went back to his tech job east of Seattle, he felt the first signs of a cough not a bad one, not enough to send him home. He attended a group lunch with colleagues that week at a seafood restaurant near his office. As his symptoms got worse, he went grocery shopping near his home.

Days later, after the man became the first person in the United States to test positive for the coronavirus, teams from federal, state and local agencies descended to contain the case. Sixty-eight people the ride-share driver at the airport, the lunchmates at the seafood restaurant, the other patients at the clinic where the man was first seen were monitored for weeks. To everyones relief, none ever tested positive for the virus.

But if the story ended there, the arc of the coronaviruss sweep through the United States would look much different.

As it turned out, the genetic building block of the virus detected in the man who had been to Wuhan would become a crucial clue for scientists who were trying to understand how the pathogen gained its first, crucial foothold.

Working out of laboratories along Seattles Lake Union, researchers from the University of Washington and the Fred Hutchinson Cancer Research Center rushed to identify the RNA sequence of the cases from Washington State and around the country, comparing them with data coming in from around the world.

Using advanced technology that allows them to rapidly identify the tiny mutations that the virus makes in its virulent path through human hosts, the scientists working in Washington and several other states made two disconcerting discoveries.

The first was that the virus brought in by the man from Wuhan or perhaps, as new data has suggested, by someone else who arrived carrying a nearly identical strain had managed to settle into the population undetected.

Then they began to realize how far it had spread. A small outbreak that had established itself somewhere north of Seattle, they realized as they added new cases to their database, was now responsible for all known cases of community transmission they examined in Washington State in the month of February.

And it had jumped.

A genetically similar version of the virus directly linked to that first case in Washington was identified across 14 other states, as far away as Connecticut and Maryland. It settled in other parts of the world, in Australia, Mexico, Iceland, Canada, the United Kingdom and Uruguay. It landed in the Pacific, on the Grand Princess cruise ship.

The unique signature of the virus that reached Americas shores in Seattle now accounts for a quarter of all U.S. cases made public by genomic sequencers in the United States.

With no widespread testing available, the high-tech detective work of the researchers in Seattle and their partners elsewhere would open the first clear window into how and where the virus was spreading and how difficult it would be to contain.

Even as the path of the Washington State version of the virus was coursing eastward, new sparks from other strains were landing in New York, in the Midwest and in the South. And then they all began to intermingle.

The researchers in Seattle included some of the worlds most renowned experts on genomic sequencing, the process of analyzing the letters of a viruss genetic code to track its mutations. Before the outbreak, one of the labs had done more sequencing of human coronaviruses than anywhere else in the world 58 of them.

When a virus takes hold in a person, it can replicate billions of times, some of those with tiny mutations, each new version competing for supremacy. Over the span of a month, scientists have learned, the version of the novel coronavirus moving through a community will mutate about twice each one a one-letter change in an RNA strand of 29,903 nucleotides.

The alterations provide each new form of the virus with a small but distinctive variation to its predecessor, like a recipe passed down through a family. The mutations are so small, however, that it is unlikely that one version of the virus would affect patients differently than another one.

The virus originated with one pattern in Wuhan; by the time it reached Germany, three positions in the RNA strand had changed. Early cases in Italy had two entirely different variations.

For each case, the Seattle researchers compile millions of fragments of the genome into a complete strand that can help identify it based on whatever tiny mutations it has undergone.

What were essentially doing is reading these small fragments of viral material and trying to jigsaw puzzle the genome together, said Pavitra Roychoudhury, a researcher for the two institutions working on the sequencing in Seattle.

With some viruses, the puzzles are more challenging to assemble. The virus that causes Covid-19, she said, was relatively well behaved.

Researchers looked closely at the man who had flown in from Wuhan, who has not been publicly identified and did not respond to a request to speak to The New York Times.

They confirmed he had brought a strain of the virus that was already extending broad tentacles from the Wuhan area to Guangdong on Chinas Pacific coast to Yunnan in the mountainous west. Along the way, its signature varied significantly from the version of the virus that spread in Europe and elsewhere: Its mutations were at positions 8,782, 18,060 and 28,144 on the RNA strand.

That gave Dr. Roychoudhury and the scientists around the country she has been working with the unique ability to see what the contact tracers in Seattle had been unable to: the invisible footprints of the pathogen as it moved.

On the hunt for the viruss path through the United States, one of the first signposts came on Feb. 24, when a teenager came into a clinic with what looked like the flu. The clinic was in Snohomish County, where the man who had traveled to China lived. Doctors gave the teenager a nasal swab as part of a tracking study that was already being done on influenza in the region.

Only later did they learn that the teenager had not had the flu, but the coronavirus. After the diagnosis, researchers in Seattle ran the sample through a sequencing machine. Trevor Bedford, a scientist at the Fred Hutchinson Cancer Research Institute who studies the spread and evolution of viruses, said he and a colleague sipped on beers as they waited for the results to emerge on a laptop.

It confirmed what they had feared: The case was consistent with being a direct descendant of the first U.S. case, from Wuhan.

The teenager had not been in contact with the man who had traveled to Wuhan, so far as anyone knew. He had fallen ill long after that man was no longer contagious.

Additional sequencing in the days afterward helped confirm that other cases emerging were all part of the same group. This could only mean one thing: The virus had not been contained to the traveler from Wuhan and had been spreading for weeks. Either he had somehow spread it to others, or someone else had brought in a genetically identical version of the virus.

That latter possibility has become more likely in recent days, after new cases entered into the researchers database showed an interesting pattern. A virus with a fingerprint nearly identical to the Wuhan travelers had shown up in cases in British Columbia, just across the border from Washington State, suggesting to Dr. Bedford that it might not have been the first Wuhan traveler who had unleashed the outbreak.

Either way, the number of cases emerging around the time the teenagers illness was identified indicated that the virus had been circulating for weeks.

On its path through Washington State, one of the viruss early stops appears to have been at a square dance on Feb. 16 in the city of Lynnwood, midway between Seattle and Everett.

It was a full month since the Wuhan travelers arrival. A couple dozen square dancers had gathered for a pie and ice cream social, capping off a series of practices and events from all over the region over the course of a three-day weekend.

Three groups of square dancers swung through promenades and allemandes huffing and sweating to Free Ride and Bad Case of Loving You.

Stephen Cole, who was the dance caller that night, said he did not recall anyone showing signs of illness. But over the next few days, he and a woman who had been cuing the dance fell ill.

Another dancer, Suzanne Jones, had attended a class with Mr. Cole the day before. By the next weekend, Ms. Jones said, she started to feel symptoms she dismissed as allergies, since she had noticed the scotch broom starting to bloom.

After resting for a couple of days, Ms. Jones felt better and drove from her home in Skagit County more than 100 miles south to visit her mother in Enumclaw, helping pack some belongings for storage. On the way back, she visited the strip malls in Renton, then a store in Everett, then a laundromat in Arlington. She stopped to apply for a job with the Census Bureau.

I probably exposed a lot of people that day, she said.

Ms. Jones only realized it could be something more than allergies after getting a notification on March 2 that one of her square-dancing friends had died of the coronavirus as the outbreak began to emerge. She too tested positive.

There was minimal coronavirus testing in the United States during February, leaving researchers largely blind to the specific locations and mutations of the spread that month. The man who had traveled from Wuhan was not at the dance, nor was anyone else known to have traveled into the country with the coronavirus. But researchers learned that the virus by then was already spreading well beyond its point of origin and all the cases of community transmission that month were part of that same genetic branch.

There was another spreading event. On the Saturday after the dance, a group of friends packed the living room of a one-bedroom apartment in Seattle, sharing homemade food and tropical-themed drinks.

Over the following days, several people began coming down with coronavirus symptoms. Among people who attended, four out of every 10 got sick, said Hanna Oltean, an epidemiologist with the Washington State Department of Health.

Several people passed on the virus to others. By late March, the state health department had documented at least three generations of transmission occurring before anyone was symptomatic, Ms. Oltean said.

By then, it was becoming clear that there were probably hundreds of cases already linked to the first point of infection that had been spreading undetected. It left a lingering question: If the virus had this much of a head start, how far had it gone?

As cases of the virus spread, scientists in other states were sequencing as many as they could. In a lab at the University of California, San Francisco, Dr. Charles Chiu looked at a range of cases in the Bay Area, including nine passengers from the Grand Princess cruise ship, which had recently returned from a pair of ill-fated sailings to Mexico and Hawaii that left dozens of passengers infected with the coronavirus.

Dr. Chiu was stunned by his results: Five cases in the San Francisco area whose origins were unknown were linked back to the Washington State cluster. And all nine of the Grand Princess cases had a similar genetic link, with the same trademark mutations plus a few new ones. The massive outbreak on the ship, Dr. Chiu believed, could probably be traced to a single person who had developed an infection linked to the Washington State cluster.

But it did not stop with the Grand Princess. David Shaffer, who had been on the first leg of the cruise with members of his family, said passengers on that leg did not discover until after they disembarked that the coronavirus had been aboard when they learned that a fellow passenger had died.

He and his family felt fine when they returned to their home in Sacramento, he said, and when he started feeling sick the next day, on Feb. 22, he at first assumed it was a sinus infection.

Days later, he was tested and learned he had the coronavirus. His wife later tested positive, too, as did one of his sons and one of his grandsons, who had not been on the cruise.

Dr. Chiu remembers going over the implications in his head. If its in California and its in Washington State, its very likely in other states.

The same day Mr. Shaffer got sick, another person landed at Raleigh-Durham International Airport in North Carolina, having just visited the Life Care Center nursing home in Kirkland, which would become a center of infection. At the time, there were growing signs of a respiratory illness at the facility, but no indication of the coronavirus.

A few days later, the traveler began feeling ill, but with no sign that it might be anything serious, he went out for dinner at a restaurant in Raleigh. Just then, officials in Washington State began to report a coronavirus outbreak at Life Care Center. The person in North Carolina tested positive a few days later the first case in the state.

By the middle of March, a team at Yale gathered nine coronavirus samples from the Connecticut region and put them through a portable sequencing machine. Seven came back with connections to Washington State.

I was pretty surprised, said Joseph Fauver, one of the researchers at the lab. At the time, he said, it suggested that the virus had been spreading more than people had initially believed.

In sequencing more recent cases, the researchers have found cases emanating from a larger cluster, with its own distinct genetic signature, originating in the New York area.

A group of cases throughout the Midwest, first surfacing in early March, appears to have roots in Europe. A group of cases in the South, which emerged around the same time, on March 3, appears like a more direct descendant from China.

But of all the branches that researchers have found, the strain from Washington State remains the earliest and one of the most potent.

It has surfaced in Arizona, California, Connecticut, the District of Columbia, Florida, Illinois, Michigan, Minnesota, New York, North Carolina, Oregon, Utah, Virginia, Wisconsin and Wyoming, and in six countries.

And new cases are still surfacing.

One of the enduring mysteries has been just how the virus managed to gain its first, fatal foothold in Washington.

Did the contact tracers who followed the steps of the man who had traveled from Wuhan miss something? Did he expose someone at the grocery store, or touch a door handle when he went to the restaurant near his office?

In recent days, the sequencing of new cases has revealed a surprising new possibility. A series of cases in British Columbia carried a genetic footprint very similar to the case of the Wuhan traveler. That opened up the possibility that someone could have carried that same branch of the virus from Wuhan to British Columbia or somewhere else in the region at nearly the same time. Perhaps it was that person whose illness had sparked the fateful outbreak.

But who? And how? That would probably never be known.

Mike Baker reported from Seattle and Sheri Fink from New York.

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Covid-19 Arrived in Seattle. Where It Went From There Stunned the Scientists. - The New York Times

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Is It Too Late to Buy Shares of Seattle Genetics? – Motley Fool

Thursday, April 23rd, 2020

As the overall market declined amid the coronavirus outbreak, Seattle Genetics (NASDAQ:SGEN) shares resisted, climbing22% since the start of this year. The reason is simple: It's all about products. Seattle Genetics started the year with a newly approved drug -- Padcev, for the most common form of bladder cancer -- and investors were hopeful the U.S. Food and Drug Administration would soon approve the company's breast cancer drug, tucatinib, to be commercialized as Tukysa. Last week, that approval came -- four months earlier than expected.

Now the question is: Can Seattle Genetics move higher, or is the good news priced into the shares at this point? A look at approved treatments and market sizes can offer us some clues.

Image source: Getty Images.

Just a year ago, Seattle Genetics was a one-product company. That product -- Adcetris, for Hodgkin lymphoma -- had a particularly strong 2019 thanks to label expansions, posting a 32% increase in net salesto $627.7 million in the U.S. and Canada. Now, Seattle Genetics forecasts a slowdown in Adcetris' sales for 2020, with an increase in the range of 8% to 12%. Still, long-term growth isn't necessarily over for Adcetris as the company works to establishthe treatment as the standard of care in Hodgkin lymphoma and expand its uses.

A slowdown in growth for Adcetris is also less of a concern given the approvals of Padcev in December and Tukysa more recently, though it will take several quarters before these drugs can truly contribute to revenue. My eyes will be on Seattle Genetics' earnings reportApril 30 to see how Padcev fared during its first full quarter on the market.

Padcev is a treatmentfor locally advanced or metastatic urothelial (bladder) cancer. The approval pertains to adult patients who have previously been treated with both platinum-based chemotherapy and inhibitors of proteins that help cancer cells survive. The FDA recently granteda breakthrough therapy designation for an additional use, and after discussions with the regulatory body, Seattle Genetics is optimistic about a potential accelerated approval registration. That would be for the use of Padcev along with an immune therapy called pembrolizumab as a first-line treatment for patients with advanced forms of urothelial cancer who can't receive chemotherapy treatments that use a common treatment called cisplatin.

If sales predictions are correct, Padcev may be poised to be a blockbuster. Analysts from SVB Leerink Research predict peak sales of more than $5 billion, according to press reports. And according to Grand View Research, the global urothelial cancer drug market will reach $3.6 billion by 2023, with a compounded annual growth rate of 23%.

Tukysa might be another blockbuster opportunity. SVB Leerink expectsthat drug to generate peak sales of $1.2 billion by 2030. Tukysa is approvedin combination with trastuzumab and capecitabine for advanced or metastatic HER2-positive breast cancer. In HER2-positive breast cancer, high levels of the HER2 protein within tumors lead to the spread of cancer cells. Tukysa inhibits enzymes that activate this type of protein. A GlobalData report shows the market for HER2-positive breast cancer is set to increase 54% to $9.89 billion by 2025 from 2015.

Seattle Genetics also has about 15 programs in phase 1 or phase 2 trials among its pipeline, adding to future revenue prospects.

Seattle Genetics has steadily grown its revenuesince 2011, when Adcetris was first approved. The company's net lossnarrowed last year to $158.7 million from $222.7 million in 2018, and after fiveconsecutive quarterly losses, Seattle Genetics posted a profit in the last quarter of 2019. The company also reported an increase in cash levels, starting this year with $868.3 million in cashand investments compared with $459.9 milliona year earlier. The financial picture is brightening for Seattle Genetics, and the additions of Padcev and Tukysa should give it a further boost.

So, is it too late to buy Seattle Genetics stock? No. Though the shares only have to rise5.5% to reach Wall Street's average price estimate, for the long-term biotech investor, there is more to gain as the newly approved drugs begin adding to the company's revenue.

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Earth Day: The relevance of land genetics in the time of COVID-19 – CNBCTV18

Thursday, April 23rd, 2020

April 22 is celebrated as Earth Day across the world since 1970 after a UNESCO conference in San Francisco proposed a day in honour of the mother Earth a year earlier. On this day in 2016, a landmark Paris agreement -- The draft Climate Protection Treaty -- was signed by the US, China and 120 other countries to protect the planet.

Come 2020 and we're all fighting an unexpected war. What is ironic, is that this war is being fought by sitting at home. Yes, the worldwide lockdown due to the coronavirus pandemic has a majority of people on the planet indoors. The condition is likened to land genetics and part of it is neuroarchitecture, which is a discipline that studies how the physical environment surrounding us can modify our brains and consequently out behavior.

Despite making ourselves busy at homes by indulging in news and entertainment on screens, most of us are facing anxiety issues.

Like the human body, planet Earth too has its anatomy, which can be positive or become sick. So while were at home, lets make use of land science and come out of this lockdown to a healthier planet. This science is purely based on geology, geography and human behaviour. Moreover, the application of land genetics can have a positive effect of our health and lives overall. The theory of land genetics suggests changes in our lifestyle -- the way we use the planet -- which can bring about a long lasting positive change.

With over 80 percent of humans locked indoors, lets consider our homes as the universe and energise the land where we live.

Here are some dos and donts according to the importance of directions that you could practice.

Sleep with your head towards the south. The head is the heaviest part of the body and acts as the North Pole and theory of physics suggests that opposite poles attract each other, this would have a calming effect on you.

If sitting for long, face the east or north, it helps you concentrate better.

A family should sleep from west to east or south to north beginning with the eldest member. The wavelength of land is bigger for elders and smaller for younger members.

If a member of the family is unwell, keep him in the first quadrant of the house which is in the north-east direction. They should sleep facing the south. It will help them fight the diseases effectively. The north-east wavelength is the smallest of all.

While cooking, one should face the north or east. This is similar to the flow of blood within the body and the magnetic force of the Earth. It helps focus and the food turns out delicious.

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Earth Day: The relevance of land genetics in the time of COVID-19 - CNBCTV18

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Genetic analysis suggests that the coronavirus was already circulating in Spain by mid-February – EL PAS in English

Thursday, April 23rd, 2020

Four pages of newsprint have the same number of letters as the genetic code of the new coronavirus: 30,000. In that brief text, there is enough information to bring the whole of humanity to its knees and force billions of people to hide away in their homes. Once the virus infects a human cell, in the throat for example, the virus is capable of reproducing up to 100,000 times in just 24 hours. Each copy can contain small errors of one letter for another and the new viruses inherit these. The history of the pandemic can be reconstructed by studying these errors.

A team of scientists from Madrids Carlos III Health Institute has analyzed the first 28 genomes of the virus in Spain. The trail of the errors does not lead to a single patient zero, but confirms that there were a multitude of entries by people who had been infected in other countries during the month of February, according to the bioinformatic specialist Francisco Dez, the first signatory of the study.

Based on the information we have today, we believe that there were at least 15 different entries in Spain

On February 23, Fernando Simn, the director of the Health Ministrys Coordination Center for Health Alerts, stated that the virus is not in Spain, nor is the disease being transmitted, nor do we currently have any cases. But it would appear that by that point the virus was already spreading unimpeded.

Dezs team has studied the nearly 1,600 complete virus genomes read by the international scientific community up until the end of March. The analysis shows that the 28 Spanish genomes belong to the three main virus families identified in the rest of the world, which are named S, G and V.

All of the viruses are very similar, in principle, with few mutations that differentiate them, which is good news, with all due care, explains Dez, who is now working at the Clnic Hospital in Barcelona. The experimental vaccines that are being investigated today are being conceived for the current genetic sequence of the virus. A high rate of mutation could ruin the efficiency of the first vaccines, which are due to arrive within a year at the earliest.

The new analysis, which has been published in an open repository and has not been externally reviewed, suggests that the common ancestor of the 1,600 viruses was in the Chinese city of Wuhan around November 24. Thirteen of the Spanish genomes belong to the S family and 11 are linked to a prior case detected on February 1 in Shanghai. The first three S viruses identified in Spain are from samples taken on February 26 and 27 in Valencia. A week before, 2,500 soccer fans from the region had traveled to Milan to see Atalanta play Valencia, an event that was described as a biological bomb by the mayor of Bergamo, Giorgio Gori.

However, genetic analysis suggests that the coronavirus from the S family was already circulating in Spain, around February 14. Another group of half a dozen cases in Madrid suggest that the G family was already circulating in the capital around February 18.

It would appear that by February 23 the coronavirus was already spreading unimpeded in Spain

The study allows for the invisible and explosive dissemination of the virus to be seen. The case of Shanghai on February 1 is apparently related to another two samples taken in France on February 25 and 26, another in Madrid on March 2, another in Chile on March 3, another in the United States on March 4, another in Georgia on March 8 and another in Brazil on March 16. The probable transmission routes become more complicated until they form a web on the world map. Dez believes that this specific branch of the virus went from Spain to another six countries.

There was no patient zero in Spain, says virologist Jos Alcam, who supervised the study along with his colleague, Inmaculada Casas. There is no patient zero when an epidemic is already so widespread. The team of geneticist Fernando Gonzlez Candelas, from the Valencian foundation Fisabio, sequenced the first three Spanish genomes of the virus on March 17. His group has now read more than a hundred. Based on the information we have today, we believe that there were at least 15 different entries in Spain. Something similar has happened in other countries, such as the US and Iceland, where multiple entries of the virus have also been identified, Gonzlez explains. Patient zero does not exist.

Gonzlez points to the limitations of these genetic studies, which are based on the complete genomes of the virus published by the scientific community in the Gisaid open repository. There are already 11,000 complete genomes from half of the world, 150 of them from Spain. But there are essential pieces missing. There are no relevant sequences from Italy in order to reach conclusions, Gonzlez complains. Without these genomes, possible routes of transmission from Italy to the rest of the world are invisible. Whats more, the image is always incomplete: there are 2.4 million confirmed cases on the planet, according to the latest data from the World Health Organization (WHO).

The Fisabio geneticist, who did not take part in the new study, is also optimistic on seeing the low diversity of the virus. SARS-CoV-2 has a mutation rate that is a thousand times slower than the flu or HIV, he says. In principle, this is good news.

Just 82 days have passed since, on February 1, the first coronavirus case was detected in Spain. The patient in question was a German tourist on the Canary Island of La Gomera. The man was linked to one of the first known outbreaks in Europe, that of a group of employees from the motor vehicle product company Webasto, who had taken part in a training course in Munich together with a Chinese colleague who had family in Wuhan.

The coronavirus, however, had already been circulating for some days, according to the genetic and epidemiological data. No border has been able to stop the virus, explains geneticist Fernando Gonzlez Candelas, from the Fisabio foundation.

The European Center for Disease Prevention and Control warned on January 18 that Wuhan airport had six weekly direct flights to Paris, three to London and another three to Rome. That was how a multitude of patient zeros traveled.

English version by Simon Hunter.

Given the exceptional circumstances, EL PAS is currently offering all of its digital content free of charge. News related to the coronavirus will continue to be available while the crisis continues.

Dozens of journalists are working non-stop to bring you the most rigorous coverage possible and meet their mission of providing a public service. If you want to support our journalism, you can do so here for 1 for the first month (10 from June). Subscribe to the facts.

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Genetic analysis suggests that the coronavirus was already circulating in Spain by mid-February - EL PAS in English

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