What We Know about Long COVID So Far

This syndrome is getting to be just a little bit creepy — especially for those of us who are under 50 (–as well as those over 50 who sometimes feel like we’re still younger than 50). 😉
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What We Know about Long COVID So Far

Maggie Fox

September 27, 2022

Editor’s note: Find the latest long COVID news and guidance in Medscape’s Long COVID Resource Center.

Long COVID: The name says it all. It’s an illness that, for many people, has not yet stopped.

Eric Roach became ill with COVID-19 in November 2020, and he’s still sick. “I have brain fog, memory loss,” says the 67-year-old Navy veteran from Spearfish, SD. “The fatigue has just been insane.”

Long COVID, more formally known as post-acute sequelae of COVID (PASC), is the lay term to describe when people start to recover, or seem to recover, from a bout of COVID-19 but then continue to suffer from symptoms. For some, it’s gone on for 2 years or longer. While the governments of the U.S. and several other countries formally recognize the existence of long COVID, the National Institutes of Health (NIH) has yet to formally define it. There’s no approved treatment, and the causes are not understood.

Here’s what is known: Long COVID is a post-viral condition affecting a large percentage of people who become infected with the coronavirus. It can be utterly debilitating or mildly annoying, and it is affecting enough people to cause concern for employers, health insurers, and governments.

First, the Many Symptoms

According to the CDC, long COVID symptoms may include:

Tiredness or fatigue that interferes with daily life
Symptoms that get worse after physical or mental effort (also known as “post-exertional malaise”)
Fever
Difficulty breathing or shortness of breath
Cough
Chest pain
Fast-beating or pounding heart (heart palpitations)
Difficulty thinking or concentrating (sometimes referred to as “brain fog”)
Headache
Sleep problems
Dizziness when standing
Pins-and-needles feelings
Change in smell or taste
Depression or anxiety
Diarrhea
Stomach pain
Joint or muscle pain
Rash
Changes in menstrual cycles

“People with post-COVID conditions may develop or continue to have symptoms that are hard to explain and manage,” the CDC says on its website. “Clinical evaluations and results of routine blood tests, chest x-rays, and electrocardiograms may be normal. The symptoms are similar to those reported by people with ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome) and other poorly understood chronic illnesses that may occur after other infections.”

Doctors may not fully appreciate the subtle nature of some of the symptoms.

“People with these unexplained symptoms may be misunderstood by their health care providers, which can result in a long time for them to get a diagnosis and receive appropriate care or treatment,” the CDC says.

Health professionals should recognize that long COVID can be disabling,the U.S. Department of Health and Human Services says. “Long COVID can substantially limit a major life activity,” HHS says in civil rights guidance. One possible example: “A person with long COVID who has lung damage that causes shortness of breath, fatigue, and related effects is substantially limited in respiratory function, among other major life activities,” HHS says.

How Many People Are Affected?

This has been difficult to judge because not everyone who has had COVID-19 gets tested for it and there are no formal diagnostic criteria yet for long COVID. The CDC estimates that 19% of patients in the U.S. who have ever had COVID-19 have long COVID symptoms.

Some estimates go higher. A University of Oxford study in September 2021 found more than a third of patients had symptoms of long COVID between 3 months and 6 months after a COVID-19 diagnosis. As many as 55% of COVID-19 patients in one Chinese study had one or more lingering symptoms 2 years later, Lixue Huang, MD, of the China-Japan Friendship Hospital in Beijing, and colleagues reported in the journal Lancet Respiratory Medicine in May.

According to the CDC, age is a factor. “Older adults are less likely to have long COVID than younger adults. Nearly three times as many adults ages 50-59 currently have long COVID than those age 80 and older,” the CDC says. Women and racial and ethnic minorities are more likely to be affected.

Many people are experiencing neurological effects, such as the so-called brain fog, according to Ziyad Al-Aly, MD, of the Washington University School of Medicine and the VA St. Louis Health Care System, writing in the journal Nature Medicine in September. They estimated that 6.6 million Americans have brain impairments associated with COVID infection.

“Some of the neurologic disorders reported here are serious chronic conditions that will impact some people for a lifetime,” they wrote. “Given the colossal scale of the pandemic, and even though the absolute numbers reported in this work are small, these may translate into a large number of affected individuals around the world — and this will likely contribute to a rise in the burden of neurologic diseases.”

Causes

It’s not clear what the underlying causes are, but most research points to a combination of factors. Suspects include ongoing inflammation, tiny blood clots, and reactivation of what are known as latent viruses, or those that linger quietly in your body without causing damage. In May, Brent Palmer, PhD, of the University of Colorado School of Medicine, and colleagues found people with long COVID had persistent activation of immune cells known as T-cells that were specific for SARS-CoV-2, the virus that causes COVID-19.

COVID-19 itself can damage organs, and long COVID might be caused by ongoing damage. In August, Alexandros Rovas, MD, of University Hospital Munster in Germany, and colleagues found patients with long COVID had evidence of damage to their capillaries. “Whether, to what extent, and when the observed damage might be reversible remains unclear,” they wrote in the journal Angiogenesis.

People with long COVID have immune responses to other viruses, such as Epstein-Barr — evidence that COVID-19 might reactivate latent viruses. “Our data suggest the involvement of persistent antigen, reactivation of latent herpesviruses, and chronic inflammation,” immunobiologist Akiko Iwasaki, PhD, of the Yale University School of Medicine, and colleagues wrote in a study posted in August that had not yet been peer-reviewed for publication.

This might be causing an autoimmune response. “The infection may cause the immune system to start making autoantibodies that attack a person’s own organs and tissues,” the NIH says.

There could be other factors. A study by Harvard researchers found that people who felt stressed, depressed, or lonely before catching COVID-19 were more likely to develop long COVID afterward. “Distress was more strongly associated with developing long COVID than physical health risk factors such as obesity, asthma, and hypertension,” Siwen Wang, MD, a research fellow with Harvard University’sT.H. Chan School of Public Health, said in a statement. Plus, nearly 44% of those in the study developed COVID-19 infections after having been assessed for stress, Wang and colleagues reported in the journal JAMA Psychiatry.

Vaccine Protection

There’s evidence that vaccination protects against long COVID, both by preventing infection in the first place, but also even for people who have breakthrough infections.

A meta-analysis covering studies involving 17 million people found evidence vaccination might reduce the severity of COVID-19 or might help the body clear any lingering virus after an infection.

“Overall, vaccination was associated with reduced risks or odds of long COVID, with preliminary evidence suggesting that

two doses are more effective than one dose,” Cesar Fernandez de las Penas, PhD, of King Juan Carlos University in Madrid, Spain, and colleagues wrote.

A team in Milan, Italy, found unvaccinated people in their study were nearly three times as likely to have serious symptoms for longer than 4 weeks compared to vaccinated volunteers. Writing in July in The Journal of the American Medical Association, Elena Azzolini, MD, PhD, an assistant professor atthe Humanitas Research Hospital, said the team found two or three doses of vaccine reduced the risk of hospitalization from COVID to 16% or 17% compared to 42% for the unvaccinated.

Treatments

With no diagnostic criteria and no understanding of the causes, it’s hard for doctors to determine treatments.

Most experts dealing with long COVID, even those at the specialty centers that have been set up at hospitals and health systems in the U.S.,recommend that patients start with their primary care doctor before moving on to specialists.

“The mainstay of management is supportive, holistic care, symptom control, and detection of treatable complications,” Trish Greenhalgh, MD, professor of primary care health sciences at the University of Oxford, and colleagues wrote in the journal The BMJ in September. “Patients with long COVID greatly value input from their primary care clinician. Generalist clinicians can help patients considerably by hearing the patient’s story and validating their experience … (and) making the diagnosis of long COVID (which does not have to be by exclusion) and excluding alternative diagnoses.”

Evidence is building that long COVID closely resembles other post-viral conditions — something that can provide clues for treatment. For example, several studies indicate that exercise doesn’t help most patients.

But there are approaches that can work. Treatments may include pulmonary rehabilitation; autonomic conditioning therapy, which includes breathing therapy; and cognitive rehabilitation to relieve brain fog. Doctors are also trying the antidepressant amitriptyline to help with sleep disturbances and headaches; the antiseizure medication gabapentin to help pain, numbness, and other neurological symptoms; and drugs to relieve low blood pressure in patients experiencing postural orthostatic tachycardia syndrome (POTS).

The NIH is sponsoring studies that have recruited just over 8,200 adults. And more than two dozen researchers from Harvard; Stanford; the University of California, San Francisco; the J. Craig Venter Institute; Johns Hopkins University; the University of Pennsylvania; Mount Sinai Hospitals; Cardiff University; and Yale announced in September they were forming the Long COVID Research Initiative to speed up studies.

The group, with funding from private enterprise, plans to conduct tissue biopsy, imaging studies, and autopsies and will search for potential biomarkers in the blood of patients.

Sources

CDC: “Long COVID or Post-COVID Conditions.”

CDC National Center for Health Statistics: “Nearly One in Five American Adults Who Have Had COVID-19 Still Have ‘Long COVID.'”

National Institutes of Health: “Long COVID,” “Long COVID symptoms linked to inflammation.”

PLoS Medicine: “Incidence, co-occurrence, and evolution of long-COVID features: A 6-month retrospective cohort study of 273,618 survivors of COVID-19.”

The Lancet Respiratory Medicine: “Health outcomes in people 2 years after surviving hospitalisation with COVID-19: a longitudinal cohort study.”

Angiogenesis: “Persistent capillary rarefication in long COVID syndrome.”

PLoS Pathogens: “SARS-CoV-2-specific T cells associate with inflammation and reduced lung function in pulmonary post-acute sequalae of SARS-CoV-2.”

Lancet eClinical Medicine: “Impact of COVID-19 vaccination on the risk of developing long-COVID and on existing long-COVID symptoms: A systematic review.”

JAMA Psychiatry: “Associations of Depression, Anxiety, Worry, Perceived Stress, and Loneliness Prior to Infection With Risk of Post–COVID-19 Conditions.”

U.S. Department of Health and Human Services: “Guidance on ‘Long COVID’ as a Disability Under the ADA, Section 504, and Section 1557.”

Long COVID Research Initiative:”Introducing LCRI.”

Nature Medicine: “Long-term Neurologic Outcomes of COVID-19.”

The BMJ: “Long COVID—an update for primary care.”

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Geneticist who unmasked lives of ancient humans wins the 2022 Nobel Prize in Physiology or Medicine

Because these GEITP pages have been sharing many of Svante Pääbo’s exciting breakthrough publications — over the past 14 years — we believe it is only appropriate to report on his winning the 2022 Nobel in Physiology or Medicine this past week. 😊 This [below] is a recent summary in the latest issue of Nature.
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Svante Pääbo has made stunning discoveries about human evolution using ancient DNA — and his work helped to spawn the competitive field of palaeogenomics.
Svante Pääbo has been awarded a Nobel prize for discoveries about the genomes of extinct hominins and human evolution.

The 2022 Nobel Prize in Physiology or Medicine has been awarded for pioneering studies of human evolution that harnessed precious snippets of DNA found in fossils that are tens of thousands of years old.

The work of Svante Pääbo, a geneticist at the Max Planck Institute for Evolutionary Anthropology (MPI-EVA) in Leipzig, Germany, led to the sequencing of the Neanderthal genome and the discovery of a new group of hominins called the Denisovans, and also spawned the fiercely competitive field of palaeogenomics.

By tracing how genes flowed between ancient hominin populations, researchers have been able to trace these groups’ migrations, as well as the origins of some aspects of modern human physiology, including features of the immune system and mechanisms of adaptation to life at high altitudes.

Pääbo’s Nobel win “is an extraordinary recognition of this field maturing and of what he did in putting together everything that needed to be done to accomplish this miracle, which is getting ancient DNA from human remains”, says David Reich, a population geneticist at Harvard Medical School in Boston, Massachusetts, who worked closely with Pääbo on the Neanderthal genome sequence.

At a press conference following the announcement, Pääbo said that he was still digesting the news, and didn’t initially believe he had won the Nobel when he got the call from Stockholm. He “at first thought it was an elaborate prank developed by people in my group”.

Chris Stringer, a palaeoanthropologist at the Natural History Museum in London, says that Pääbo’s work — including recovery of the oldest ancient human DNA on record, 430,000-year-old sequences from Spain1 — has revolutionized our understanding of the past. “It’s central to human evolutionary studies now,” Stringer says, adding that the Nobel win is “great news”.
Damaged DNA

Pääbo had to develop ways of analysing DNA that had been damaged by thousands of years of exposure to the elements, and contaminated with sequences from microorganisms and modern humans. He and his collaborators then put these techniques to work sequencing the Neanderthal genome, which was published in 20102. This genetic analysis led to the finding that Neanderthals and Homo sapiens interbred, and that 1–4% of the genome of modern humans of European or Asian descent can be traced back to the Neanderthals.

Pääbo’s techniques were also used to identify the origins of a 40,000-year-old finger bone found in a southern Siberian cave in 2008. DNA isolated from the bone indicated that it was from neither Neanderthals nor Homo sapiens, but came from an individual belonging to a new group of hominins3. The group was named the Denisovans, after the cave in which the bone was found. Ancient humans living in Asia interbred with this group, too, and Denisovan DNA can be found in the genomes of billions of people alive today.

During the early years of ancient DNA research — led by Pääbo and other scientists in the 1980s and 1990s — the field was plagued by concerns over contamination from modern human DNA (Pääbo has admitted that DNA he recovered early on from Egyptian mummy remains was probably his own). But, thanks to methods developed in Pääbo’s laboratory, as well as the advent of new sequencing technologies, contamination is no longer the ‘boogeyman’ it once was.

“When I started, we weren’t even sure you could work with ancient human DNA,” says Pontus Skoglund, a palaeogeneticst at the Francis Crick Institute in London. “But now, and I think led by Svante’s department, we have an approach where contamination is really not a major issue anymore.”
Health implications

Pääbo’s work teasing out DNA from Neanderthals, Denisovans and other hominins also has important implications for modern medicine. Although the proportion of the human genome comprised of archaic DNA is small, this material seems to punch above its weight, making an important contribution to the risks of diseases ranging from schizophrenia4 to severe COVID-195. And people living on the Tibetan Plateau can thank Denisovans for gene variants linked to high-altitude adaptation6.

“The fact that a good fraction of the people running around in the world today have DNA from archaic humans like Neanderthals is of important consequence to who we are,” says Reich. “So I think that knowing that and trying to understand the implications of that for health is something that will be with us for the rest of our time as a species.”

With genomes from multiple Neanderthals and Denisovans available, it is now possible to identify uniquely human genes, says Johannes Krause, a palaeogeneticist at MPI-EVA. In September, researchers showed that a gene variant found in humans, but not in Neanderthals or Denisovans, is linked to greater neuronal growth in lab-grown brain organoids7. “We’ve never come so close to understanding what makes humans humans,” Krause says.

Researchers describe Pääbo as intense and driven, but also collegial and generous. His department at the Max Planck Institute for Evolutionary Anthropology has produced a generation of palaeogeneticists who are pushing the field ever further.

Viviane Slon, a palaeogeneticist at Tel Aviv University in Israel who did her PhD under Pääbo’s supervision, says her former mentor has an “uncanny” ability to see the larger picture while remaining laser-focused on details. When Slon was working on remains that turned out to be a first-generation Denisovan–Neanderthal hybrid, the sequence of maternally inherited mitochondrial DNA matched that of a Neanderthal. But, when publishing those results, Pääbo urged Slon to reserve judgment until they had sequenced nuclear DNA inherited from both parents. “He wouldn’t let me write that it’s a Neanderthal because we didn’t know that, and in fact it turned out to be a mixed offspring,” Slon says.

Reich says that working with Pääbo and the team he organized to sequence and analyse the first Neanderthal genome was inspirational. “It was the best consortium ever,” Reich says. “He recognized how special and unique this type of data they were producing was.” This eventually inspired Reich to set up his own ancient DNA laboratory.

Pääbo’s influence on ancient DNA work has been such that it’s hard to imagine where the field would be without him. “He’s the godfather of the field,” says Skoglund.

Nature 610, 16-17 (2022)

doi: https://doi.org/10.1038/d41586-022-03086-9
References

Meyer, M. et al. Nature 531, 504–507 (2016).

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Green, R. E. et al. Science 328, 710–722 (2010).

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Krause, J. et al. Nature 464, 894–897 (2010).

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Gregory, M. D. et al. Am. J. Med. Genet. B Neuropsychiatr. Genet. 186, 329–338 (2021).

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Zeberg, H. & Pääbo, S. Nature 587, 610–612 (2020).

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Huerta-Sánchez, E. et al. Nature 512, 194–197 (2014).

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Pinson, A. et al. Science 377, eabl6422 (2022).

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Major Scientific Publisher Retracts More Than 500 Papers

Along with the themes of “gene-environment interactions” and “evolution” — GEITP emails over the past 14+ years include, from time-to-time, breaking news on “fraud and corruption in science.” This winning article, just published in The Epoch Times, qualifies for sharing with all GEITP recipients(!!). 😉 Certainly, many more salacious follow-up articles on this investigation will be summarized in highly-visible scientific journals (especially Science and Nature). 😊
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Major Scientific Publisher Retracts More Than 500 Papers

By Zachary Stieber

October 2, 2022

One of the world’s largest open-access journal publishers is retracting more than 500 papers, based on the discovery of unethical actions.

London-based Hindawi, which publishes more than 200 peer-reviewed journals across multiple disciplines, stated that its research team identified in June “irregularities” in the peer review process in some of the journals.

“All Hindawi journals employ a series of substantial integrity checks before articles are accepted for publication. Following thorough investigation, we identified that these irregularities in the peer review process were the result of suspicious and unethical activities. Since identifying this unethical activity and breach of our processes, we began proactively adding further checks and improving our processes and continue to do so,” Liz Ferguson, a senior vice president for John Wiley & Sons, Hindawi’s U.S.-based parent company, said in a Sept. 28 statement.

As a result of the investigation, 511 papers (so far) will be retracted.

The papers have all been published since August 2020.

Sixteen journals published the papers that are being retracted.

Some of the coauthors and editors who contributed to the articles may have been “unwitting participants” in the unethical scheme, according to Ferguson. She said the scheme involved “manipulation of the peer review process and the infrastructure that supports it.”

Richard Bennett, vice president of researcher and publishing services for Hindawi, told the Retraction Watch blog that the review uncovered “coordinated peer-review rings” — which featured reviewers and editors coordinating to get papers through peer review.

Neither Ferguson nor Bennett identified any of the suspects.

Bennett said the investigation started after an editor flagged some suspicious papers. He also said all the individuals identified by the review as “compromised” will be banned from Hindawi journals in the future. Other people were described as “potentially compromised.”

“These efforts, and the individuals who participate in them, impede scientific discovery and impact the validity of scholarly research and will not be tolerated,” Ferguson said.

She also said the company has been in touch with other publishers and industry bodies.

Further retractions are expected as the investigation proceeds.

Hindawi journals include Advances in Agriculture, the Canadian Journal of Infectious Diseases and Medical Microbiology, and the Journal of Nanotechnology.

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NASA flies its spacecraft into asteroid in direct hit

Web site from my astronomy son, David.

This project is SO cool. SO amazing all this could be done (from millions of miles away)

Dimorphos: NASA flies its spacecraft into asteroid in direct hit

Jonathan Amos

Science correspondent
@BBCAmoson Twitter

The American space agency’s Dart probe has smashed into an asteroid, destroying itself in the process.

The collision was intentional and designed to test whether space rocks that might threaten Earth could be nudged safely out of the way.

Dart’s camera returned an image per second, right up to the moment of impact with the target – a 160m-wide object called Dimorphos.

What had been a steady image stream cut out as the probe was obliterated.

Both asteroids

Dart’s navigation system first had to distinguish the smaller rock (Dimorphos) from the larger one (Didymos)

Controllers, based at the Johns Hopkins University Applied Physics Laboratory (JHU-APL), erupted with joy as Dimorphos filled the field of view on Dart’s camera just before then going blank. Initial calculations suggest the impact was a mere 17 meters off the exact centre of Dimorphos.

It will be some weeks before scientists on the Nasa-led mission know for sure whether their experiment has worked, but Dr Lori Glaze, the director of planetary science at the space agency, was convinced something remarkable had been achieved.

“We’re embarking on a new era of humankind, an era in which we potentially have the capability to protect ourselves from something like a dangerous hazardous asteroid impact. What an amazing thing; we’ve never had that capability before,” she told reporters.

And Dr Elena Adams, a JHU-APL mission systems engineer, said “earthlings should sleep better” knowing they had a planetary defence solution.

Dimorphos

Dimorphos is probably a loosely consolidated collection of smaller rocks – a “rubble pile”

Researchers will determine success, or otherwise, by studying the changes to the orbit of Dimorphos around another asteroid known as Didymos.

Telescopes on Earth will make precise measurements of the two-rock, or binary, system.

Before the collision, Dimorphos took roughly 11 hours and 55 minutes to circle its 780 m-wide partner.

This ought to reduce by a few minutes following the crash.

Infographic

Certainly, on the evidence of the pictures coming back from 11 million km from Earth, everything appeared to go exactly to plan.

The Dart probe, moving at the relative velocity of 22,000 km/h, had to first distinguish the smaller rock from the larger one. Onboard navigation software then adjusted the closing trajectory with thruster firings to ensure a head-on collision.

Scientists were fascinated to see – albeit briefly – the different shapes of the two asteroids.

Dimorphos

The last whole frame to come down before the feed from Dart was abruptly lost

Didymos, as expected, had a diamond shape. There were boulders on its surface but also some smooth areas.

Dr Carolyn Ernst, the instrument scientist on Dart’s camera system, was extremely excited to see Dimorphos.

“It looks adorable; it’s this little moon; it’s so cute,” she said.

“It looks in a lot of ways like some of the other small asteroids we’ve seen, and they are also covered in boulders. So we suspect it is likely to be a rubble pile, kind of loosely consolidated.”

Infographic.

DART is an acronym for Double Asteroid Redirection Test.

It was designed to do “exactly what is says on the tin”, JHU-APL mission lead Dr Andy Rivkin told BBC News.

“This technique, called the ‘kinetic impactor technique’ could be used if there were to be an asteroid that was incoming at some point in the future. It’s a very simple idea: you ram the spacecraft into the object you’re worried about, and you use the mass and the speed of your spacecraft to slightly change the orbit of that object enough so that it would miss the Earth instead of hitting the Earth.”

Cubesat view of impact

LiciaCube saw a plume of debris enveloping Dimorphos (top). Didymos is the foreground object

Dimorphos and Didymos were carefully chosen. Neither was on a path to intersect with Earth before the demonstration, and a small alteration in their orbital relationship will not have increased the risk.

But there are rocks out there that could potentially pose a danger to us.

Although sky surveys have identified more than 95% of the monster asteroids that could initiate a global extinction were they to collide with Earth (they won’t; their paths have been computed and they won’t come near our planet), this still leaves many so-far undetected smaller objects that could create havoc, if only on the regional or city scale.

Artwork: Dart approaches Dimorphos

An object of Dimorphos’s scale would dig out a crater perhaps 1km across and a couple of hundred metres deep. The damage in the vicinity of the impact would be intense. Hence the desire to see if an asteroid can be nudged into going slightly slower or faster. The change in velocity wouldn’t have to be great, especially if done many years in advance of the expected intersection with Earth.

“An analogy is if you’re wearing a wristwatch and you damage it, and it starts running fast by a little bit,” explained Dart mission scientist Dr Nancy Chabot, also from JHU-APL. “You might not notice the error in the first day or two, but after a few weeks you will begin to notice that the watch is just not keeping correct time anymore. It’s running fast; it’s ahead of where it should be.”

Graphic: Asteroid populations

Dart’s image stream may have ended abruptly at impact, but there was a small Italian cubesat, following three minutes behind. It was snapping away at the safe distance of 50 km…!!

The LiciaCube’s data will be beamed back to Earth over the next few days.

But even in the first picture returns it was evident that the cubesat caught sight of the plume of debris dug out by Dart.

Four years from now, the European Space Agency (Esa) will have three spacecraft – collectively known as the Hera mission – at Didymos and Dimorphos to make follow-up studies.

Artwork: Hera mission

Artwork: The European Space Agency is sending three spacecraft for follow-up investigations

https://www.bbc.com/news/science-environment-63039191

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Do the JWST Images bebunk the Big Bang Theory? Or Not?

In 1931, Monseigneur Georges Henri Joseph Édouard Lemaître (b. 1894; d. 1966) put forth the idea that there was once a primordial atom which had contained all the matter in the universe. The other support for the Big Bang that LeMaitre used — was the idea of entropy, which states that “everything is moving towards greater and greater disorder” (chaos, being the ultimate steady-state).

One might conclude that COSMOLOGY is a science of opinions. There are few facts. Just some observations. 😉

DwN

answers: Pediatric endocrinologists know nothing. As a pediatric endocrinologist (who has asked these questions since the late ’50s), here are my “thoughts” (in blue font) on M’s list of questions.

[a] If “everything” started with a Big Bang, where did the original material, or the energy, come from? From what I know about physics, something cannot appear out of nothing. Ergo, there must have been something before the Big Bang. ——The mathematics (to the extent I can understand) indicates a “singularity” at time=0. “Singularity” essentially means “a discontinuity that cannot be described mathematically.” Lemaître’s “primeval atom” was a singularity of infinite mass and density with no describable dimensions. Then the Big Bang occurred.

[b] The experts claim that the universe has been expanding, ever since the Big Bang. And their calculations are able to assess the velocity by which this expansion is taking place. If this expansion is true, into what is the universe expanding? ——This question has always bothered me (as does Matti’s questions c, d, and e). I believe [which is a commonly-used term in cosmology] that all three questions have related answers. From the cradle, we have all thought in three dimensions (x, y, z axes) with a linear fourth dimension of time. The key idea that is so hard to “wrap our heads around” is that at t=0 there were NO dimensions. As the universe expanded, so did its coordinate system. Space itself expanded. Time expanded. Our classic languages lack the terms and systems to discuss the universe at t=o, when there was NO space or NO time. So, the answer to question [b] is that the universe was not expanding into something, because that something was itself expanding (quickly!).

[c] If the Big Bang had a precise time-point at which it originated, what was there before that time-point? ——There was no “before,” because time itself began at t=0.

[d] Where was the original location of the Big Bang — at the center? or at the edge of something? ——Because the Big Bang at t=0 was the beginning of both space and time (which are really one thing, Einstein called it “spaceime”) — there was no “center” or “edge.”

[e] Does that “something” (into which the debris from the Big Bang debris is expanding) have boundaries? If it does, what is beyond thosee boundaries? If it does not, can anything be limitless, without boundaries? ——There is no “something” into which “debris” from the Big Bang expands; spacetime itself expands. There are no “boundaries.” The structure of Questions c, d, and e presume what lawyers would term “facts not in evidence”; we have no evidence for there being anything — ANYTHING(!) — before t=0. Thus, there is no “before” or “beyond.”

[f] Is there a parallel universe? or a mirror-image universe?

[g] If there is more than one universe, how many universes are there? ——Questions f and g have the same answer: “God only knows, but she hasn’t told me!” Maybe my replies sound religious, but I’m old now. And that’s the best answer I can come up with. So far. 😉 😊

WM

From: Nebert, Daniel
Sent: Sunday, September 11, 2022 9:29 PM

It’s nice to know my Nordic colleagues have inquisitive minds and are asking questions about things that have no answer. 😉 All these questions posed by Matti have been asked by many scientists, ever since the Big Bang Theory was first set forth.

Perhaps the questions are “easier” — if there was not a Big Bang? Then, we might have a universe that has no beginning and no end. These galaxies might be wandering around in multiple directions, without limits. New stars form and old stars explode and die. Black holes are swallowing up all sorts of debris. These are the stuff that science-fiction novels are made of, … … … … 😊😊
DwN

From: MLg
Sent: Tuesday, August 30, 2022 4:43 AM

Hi Dan,
In my <> opinion, the science of cosmology is indeed far from settled. Most leading cosmologists are concentrating their brainpower and creating clever equations to try and explain the details of the Big Bang. Consensus appears to emerge that this event occurred about 13.8 billion years ago. However, I have a few questions about this entire phenomenon:

[a] If “everything” started with a Big Bang, where did the original material, or the energy, come from? From what I know about physics, something cannot appear out of nothing. Ergo, there must have been something before the Big Bang.

[b] The experts claim that the universe has been expanding, ever since the Big Bang. And their calculations are able to assess the velocity by which this expansion is taking place. If this expansion is true, into what is the universe expanding?

[c] If the Big Bang had a precise time-point at which it originated, what was there before that time-point?

[d] Where was the original location of the Big Bang — at the center? or at the edge of something?

[e] Does that “something” (into which the debris from the Big Bang debris is expanding) have boundaries? If it does, what is beyond thosee boundaries? If it does not, can anything be limitless, without boundaries?

[f] Is there a parallel universe? or a mirror-image universe?

[g] If there is more than one universe, how many universes are there?

This discussion to me is analogous to the question, “How many angels can dance on the head of a pin?” ☹
– – -M

From: Olavi Pelkonen Sent: Monday, August 29, 2022 11:49 PM

Dan,
I have not lost any sleep over this debate; however, it is very interesting and thought-provoking. It is a worthwhile topic for us to follow! OP

Hi Dan

Thanks for sharing this.
Indeed, very interesting!

Best, M S

From: Nebert, Daniel (nebertdw)
Sent: Monday, August 29, 2022 4:43 PM

There is no need to lose sleep over this. The “science of cosmology” — is far from settled. 😊
This article [below] was donated by Paul Kepshire (son of a friend);
and also by John Reichard, PhD (Dept Environmental & Public Health Sciences, University of Cincinnati).
DwN

No, James Webb Space Telescope Images Do Not Debunk the Big Bang
The JWST provides an intriguing look at the early universe, but it’s not yet rewriting fundamental theories of the cosmos

Jackson Ryan

Aug. 22, 2022

NASA’s James Webb Space Telescope has not provided evidence the Big Bang didn’t happen.

How did the universe come to be? The prevailing theory is everything that is — began with the Big Bang. In a nutshell, the theory suggests everything, everywhere, all at once suddenly burst to life. The caveat being everything and everywhere prior to the Big Bang is fairly hard to conceptualize.

The Big Bang theory is currently the best model we have for the birth of our universe. Astrophysicists have shown the theory explains, fairly comprehensively, phenomena we’ve observed in space over decades, like lingering background radiation and elemental abundances. It’s a robust framework that gives us a pretty good idea of how the cosmos came into being some 13.8 billion years ago.

But with the flurry of preprint papers and popular science articles about the James Webb Space Telescope’s first images, old, erroneous claims that the Big Bang never happened at all have been circulating on social media and in the press in recent weeks. One scientist has claimed that the JWST images are inspiring “panic among cosmologists” — that is, the scientists who study the origins of the universe.

This is simply not true. The JWST has not provided evidence disproving the Big Bang theory, and cosmologists aren’t panicking. Why, then, are we seeing viral social media posts and funky headlines that suggest the Big Bang didn’t happen at all?

To answer that question, and show why we should be skeptical of claims like this, we need to understand where the idea came from.
Where did “the Big Bang didn’t happen” come from?

It all started with an article at The Institute of Art and Ideas, a British philosophical organization, on Aug. 11. The piece was written by Eric Lerner, who has long argued against the Big Big theory. He even wrote a book titled The Big Bang Never Happened in 1991.

This provocatively headlined article at IAI is also related to an upcoming debate Lerner is participating in, run by the IAI, dubbed “Cosmology and the Big Bust.”

Lerner’s article gathered steam across social media, being shared widely on Twitter and across Facebook, over the last week. It makes sense why it’s caught fire: It’s a controversial idea that upends what we think we know about the cosmos. In addition, it’s tied to a new piece of technology in the James Webb telescope, which is seeing parts of the universe we’ve never been able to see before. Including Webb as the news hook here suggests there’s new data which overturns a long-standing theory.

Don’t get me wrong — there is new and intriguing data emerging from the JWST. Just not the kind that would undo the Big Bang theory. Most of this new data trickles down to the public in the form of scientific preprints, articles that are yet to undergo peer review and land on repositories like arXiv, or popular press articles.

Lerner’s piece uses some of the early JWST studies to attempt to dismiss the Big Bang theory. What’s concerning is how it misconstrues early JWST data to suggest that astronomers and cosmologists are worried the well-established theory is incorrect. There are two points early in Lerner’s article which show this:

He points to a preprint with the word “Panic!” in its title, calling it a “candid exclamation.”
He misuses a quote from Allison Kirkpatrick, an astronomer at the University of Kansas.

The first point is just a case of Lerner missing the pun. The full title of the paper is “Panic! At the Disks: First Rest-frame Optical Observations of Galaxy Structure at z>3 with JWST in the SMACS 0723 Field.” The first author of that preprint, astronomer Leonardo Ferreira, is clearly riffing on popular 2000s emo band Panic! at the Disco with his title. It’s a tongue-in-cheek reference, not a cosmological crisis.

As for the second point, Lerner takes this quote from Allison Kirkpatrick, which comes from a Nature news article published on July 27:

“Right now, I find myself lying awake at three in the morning and wondering if everything I’ve done is wrong.”

This cherrypicked quote isn’t in direct reference to the Big Bang theory. Rather, Kirkpatrick is reckoning with the first data coming back from the JWST about the early evolution of the universe. It’s true there are some puzzles for astronomers to solve here, but, so far, they aren’t rewriting the beginning of the universe to do so. Kirkpatrick has stated her quotes were misused and even changed her Twitter name to “Allison the Big Bang happened Kirkpatrick.”

“We as scientists have a responsibility to educate the public, and I take that responsibility very seriously,” Kirkpatrick told CNET. “Deliberately misleading the public makes it difficult for them to trust real scientists and to know fact from fiction.”

In addition, Lerner’s article claims that his ideas are being censored by the scientific establishment, and later he also points to his theory being important to develop fusion energy on Earth. It’s no coincidence the same paragraph links to LPPFusion, a company run by Lerner aimed at developing clean energy technologies.
Why does this matter?

One of the chief reasons the Big Bang theory stands up is because of the cosmic microwave background (CMB). This was discovered in 1964. In short, the CMB is the radiation leftover from the Big Bang, right when the universe began and scientists have been able to “see” it with satellites that can detect that lingering radiation.

So, to bolster evidence the Big Bang theory is incorrect, you’d need to explain the CMB another way. Lerner’s dismissive of the CMB, and his proposal for the observation has been disproven in the past. If you’re interested in further arguments against Lerner’s hypotheses and why the claims don’t add up, I recommend checking out Brian Keating’s recent YouTube video. Keating is a cosmologist at the University of California, San Diego, and dives into a bit more detail about the limits of Lerner’s arguments.

It’s also important to note Webb is not built to see and undertake new analyses of the CMB itself. The telescope can’t “see” that far back in time. However, it will look at an epoch a few hundred million years after the Big Bang. What it finds there will almost certainly reshape our views on the early universe, galaxies and the evolution of the cosmos. But it is disingenuous to claim the early images and study results have contradicted the Big Bang theory.

Kirkpatrick notes JWST’s images actually do the opposite. She said they “support the Big Bang model because they show us that early galaxies were different than the galaxies we see today — they were much smaller!”

Science is about making incremental progress in our understanding, coming to increasingly stronger conclusions based on observations. The observations astrophysicists and cosmologists have made over decades line up with the Big Bang theory. They don’t line up anywhere near as neatly if we use Lerner’s alternative theory. This doesn’t mean scientists won’t find evidence overturning the Big Bang theory. They just might! But, for now, it remains our best theory for explaining what we see.

Scientific theories can — and should — be challenged by well-reasoned scientists presenting highly detailed and thoughtful arguments. This is not one of those times. And that means, despite the headlines, most believe that the Big Bang did happen.

https://www.cnet.com/science/space/no-james-webb-space-telescope-images-do-not-debunk-the-big-bang/

From: Nebert, Daniel (nebertdw)
Sent: Sunday, August 28, 2022 5:37 PM

This article [below] has taken me hours to wrap my head around. The speed of light is ~186,282 miles per second — a universal constant known in equations as “c,” or “light speed” — in a vacuum. However, in the radioastronomy of pulsars, the speed of light is not constant, but rather varies by wavelength…!!

This indicates that the interstellar medium is not an electromagnetic vacuum. Therefore, at increasing distances, one’s estimates of “distance” will be less than the true distance, because the velocity of light is slowed down by intergalactic gases. The Hubble Red Shift is caused by “Tired Light,” rather than the expansion of the universe…!!

Because of what the James Webb Space Telescope (JWST) images are now telling us, cosmologists can no longer accept the hypothesis that the universe has been expanding since the “Big Bang” — which supposedly occurred ~13.8 million years ago. It needs to be pointed out that this long article is written by a cosmologist who has had trouble publishing his papers or getting funding — because he has been convinced for decades that the Big Bang did not happen. He has been censored by all mainstream journals, which hold on to “The Big Bang Hypothesis,” as if it were fact; it is not. It has never been fact. ☹

There are similarities in this field of cosmology that remind me today of the field of climatology. Will the day ever come back — when “science” returns to “facts, factual data,” and not opinions and censorship? Politics and Religion MUST be removed from math and science. ☹

DwN

The Big Bang didn’t happen ??

What do the James Webb images really show?

Deep Field James Webb min
11th August 2022

Eric J. Lerner

President and Chief Scientist of LPPFusion. He is the author of The Big Bang Never Happened.

The Big Bang Hypothesis – which states the universe has been expanding since it began ~13.8 billion years ago in a hot and dense state – is contradicted by the new James Webb Space Telescope images, writes Eric Lerner.

To everyone who sees them, the new James Webb Space Telescope (JWST) images of the cosmos are beautifully awe-inspiring. But to most professional astronomers and cosmologists, they are also extremely surprising — not at all what was predicted by theory. In the flood of technical astronomical papers published online since July 12, the authors report again and again that the images show surprisingly many galaxies, galaxies that are surprisingly smooth, surprisingly small, and surprisingly old. Lots of surprises, and not necessarily pleasant ones. One paper’s title begins with the candid exclamation: “Panic!”

Why do the JWST’s images inspire panic among cosmologists? And what theory’s predictions are they contradicting? The papers don’t actually say. The truth that these papers don’t report is that the hypothesis that the JWST’s images are blatantly and repeatedly contradicting is the Big Bang Hypothesis that the universe began ~14 billion years ago in an incredibly hot, dense state and has been expanding ever since. Since that hypothesis has been defended for decades as unquestionable truth by the vast majority of cosmological theorists, the new data are causing these theorists to panic. “Right now I find myself lying awake at three in the morning,” says Alison Kirkpatrick, an astronomer at the University of Kansas in Lawrence, “and wondering if everything I’ve done is wrong.”

The delusions of cosmology min

It is not too complicated to explain why these too small, too smooth, too old, and too numerous galaxies are completely incompatible with the Big Bang hypothesis. Let’s begin with “too small”. If the universe is expanding, a strange optical illusion must exist. Galaxies (or any other objects) in expanding space do not continue to look smaller and smaller with increasing distance. Beyond a certain point, they start looking larger and larger. (This is because their light is supposed to have left them when they were closer to us.) This is in sharp contrast to ordinary, non-expanding space, where objects look smaller in proportion to their distance.

Smaller and smaller is exactly what the JWST images show. Even galaxies with greater luminosity and mass than our own Milky Way galaxy appear in these images to be two to three times smaller than in similar images observed with the Hubble Space Telescope (HST), and the new galaxies have redshifts which are also two to three times greater.

This is not at all what is expected with an expanding universe, but it is just exactly what I and my colleague Riccardo Scarpa predicted based on a non-expanding universe, with redshift proportional to distance. Starting in 2014, we had already published results, based on HST images, that showed that galaxies with redshifts all the way up to 5 matched the expectations of non-expanding, ordinary space. So, we were confident the JWST would show the same thing — which it already has, for galaxies having redshifts as high as 12. Put another way, the galaxies that the JWST shows are just the same size as the galaxies near to us, if it is assumed that the universe is not expanding and redshift is proportional to distance.

stephan quintetmedium

But from the standpoint of the Big Bang, expanding-universe hypothesis, these distant galaxies must be intrinsically extremely tiny to compensate for the hypothesized optical illusion — implausibly tiny. One galaxy noted in the papers, called GHz2, is far more luminous that the Milky Way, yet is calculated to be only 300 light years in radius — 150 times smaller than the radius of our Milky Way. Its surface brightness — brightness per unit area — would be 600 times that of the brightest galaxy in the local universe. Its density (and that of several other galaxies in the new images) would be tens of thousands of times that of present-day galaxies.

Big Bang theorists have known for years from the HST images that their assumptions necessitate the existence of these tiny, ultra-dense “Mighty Mouse” galaxies. JWST has just made the problem far worse. The same theorists have speculated that the tiny galaxies grow up into present day galaxies by colliding with each other — merging to become more spread out. An analogy to this hypothetical merger process would be to imagine a magical toy car a centimeter long that nonetheless weighs as much as an SUV and grows up into a real SUV by colliding with many other toy cars.

But the JWST has shot through this far-out scenario as well. If you could believe the toy car story, you would at least expect some fender dents in the colliding cars. And Big Bang theorists did expect to see badly mangled galaxies scrambled by many collisions or mergers. What the JWST actually showed was overwhelmingly smooth disks and neat spiral forms, just as we see in today’s galaxies. The data in the “Panic!” article show that smooth spiral galaxies were about “10 times” as numerous as what theory had predicted and that this “would challenge our ideas about mergers being a very common process”. In plain language, these data utterly destroy the merger theory.

With few or no mergers, there is no way tiny galaxies could grow to be a hundred times bigger. Therefore, they were not tiny to begin with, and thus the optical illusion predicted from the expanding universe hypothesis does not exist. But no illusion means no expansion: the illusion is an unavoidable prediction from expansion. Thus, the panic among Big Bang supporters. Tiny and smooth galaxies mean no expansion and thus no Big Bang.

Too old and too many galaxies mean the same thing. The JWST uses many different filters to take its images in the infrared part of the spectrum. Thus, it can see the colors of the distant galaxies. This, in turn, allows astronomers to estimate the age of the stars in these galaxies because young, hot stars are blue in color and older, cooler stars, like our sun, are yellow or red in color. According to Big Bang theory, the most distant galaxies in the JWST images are seen as they were only 400-500 million years after the origin of the universe. Yet already some of the galaxies have shown stellar populations that are over a billion years old. Since nothing could have originated before the Big Bang, the existence of these galaxies demonstrates that the Big Bang did not occur.

Just as there must be no galaxies older than the Big Bang (if the Big Bang hypothesis were valid), so theorists expected that as the JWST looked out further in space and back in time, there would be fewer and fewer galaxies and eventually none — a Dark Age in the cosmos. But a paper to be published in Nature demonstrates that galaxies as massive as the Milky Way are common even a few hundred million years after the hypothesized Bang. The authors state that the new images show that there are at least 100,000 times as many galaxies as theorists predicted at redshifts more than 10. There is no way that so many large galaxies can be generated in so little time, so again — no Big Bang.

While Big Bang theorists were shocked and panicked by these new results, Riccardo and I (and a few others) were not. In fact, a week before the JWST images were released we published online a paper that detailed accurately what the images would show. We could do this with confidence because more and more data of all kinds have been contradicting the Big Bang hypothesis for years. The widely-publicized crisis in cosmology has drawn general attention to the failed predictions of the Big Bang hypothesis for the Hubble constant — elating redshift to distance. But our papers, published over the past decades, have pointed to far more contradictions, each individually acknowledged by other researchers.

Big Bang learner

The Big Bang prediction of the abundance of helium is off by a factor of two, the prediction for the abundance of lithium is off by a factor of 20. In addition to the absence of the larger-more-distant optical illusion, there is also the existence of large-scale structures too big to have formed in the times since the Big Bang, wrong predictions for the density of matter in the universe, and well-known asymmetries in the cosmic microwave background that should not exist according to theory. There are many more contradictions. In early July I published two comprehensive papers summarizing the situation. Based on the published literature, right now the Big Bang makes 16 wrong predictions and only one correct one — the abundance of deuterium, an isotope of hydrogen.

20 07 30.ekeberg.ata

Readers may well be wondering at this point why they have not read of this collapse of the Big Bang hypothesis in major media outlets by now and why the authors of so many recent papers have not pointed to this collapse themselves. The answer lies in what I term the “Emperor’s New Clothes Effect” — if anyone questions the Big Bang, they are labeled stupid and unfit for their jobs. Unfortunately, funding for cosmology comes from a very few government sources controlled by a handful of committees that are dominated by Big Bang theorists. These theorists have spent their lives building the Big Bang theory. Those who openly question the theory simply don’t get funded.

Until the past few years, if researchers could self-fund cosmology research as a sideline, as is the case with me, they still could publish “heretical” papers, although those papers were often ignored by the cosmological establishment. As recently as 2018, the Monthly Notices of the Royal Astronomical Society (MNRAS), a leading journal, published one of my papers showing how the sizes of galaxies contradicted the expanding universe idea.

But as the crisis in cosmology became obvious in 2019, the cosmological establishment has circled the wagons to protect this failed theory with censorship, because it now has no other defense. It has now become almost impossible to publish papers critical of the Big Bang in any astronomical journals. An anonymous senior editor rejected my survey papers, writing “There are many journals which would be interested in publishing a well-argued synthesis of existing evidence against the standard hot big bang interpretation. But MNRAS, with its focus on publication of significant new astronomical results, is not one of them”. The replies from several other journals were similar.

Such censorship is now, as always, hostile to the progress of science. Two dozen researchers in astrophysics, astronomy and space science have signed a letter of protest to the arXiv leadership. I have personally called on leading Big Bang theorists to openly debate the new evidence. For cosmology — as for any research area, including the silly hypothesis that “there is a climate crisis” — to advance, this debate must happen openly in both scientific journals and the public media.

These scientific questions matter in the here and now. Over decades scientists, starting with Physics Nobel Laureate Hannes Alfven, have shown that if the Big Bang hypothesis is thrown out, the evolution of the cosmos and the phenomena that we observe today, like the cosmic microwave background, can be explained using the physical processes we observe in the laboratory — especially the electromagnetic processes of plasmas. Plasma is the electrically conducting gas that makes up nearly all the matter that we see in space, in the stars and in the space between the stars. Only the Hubble redshift relation would still need some new physical process to explain the loss of energy as light travels huge distances.

One of the key processes in plasmas that Alfven and his colleagues identified, and which has been studied for 50 years, is plasma filamentation. This is the process by which electric currents, and the magnetic fields they create, draw plasma into the lacy system of filaments that we see at all scales in the universe from the aurorae in the earth’s atmosphere to the solar corona to galactic spiral arms, even to clusters of galaxies. Together with gravitational forces, plasma filamentation is one of the basic processes in the formation of planets, stars, galaxies and structures at all scales.

That process of plasma filamentation is also key to the enormously important effort to develop fusion energy here on earth. To use fusion energy, the power that drives the universe and gives light to the Sun and all the stars, we need to understand the processes that drive cosmic evolution. Just as the Wright Brothers developed the airplane by studying how birds controlled their flight, so today we can only control the ultra-hot plasma where fusion reactions occur by studying how plasmas behave at all scales in cosmos.

We need to imitate nature, not try to fight it. We at LPPFusion have been applying that knowledge concretely to the development of a cheap, clean and unlimited source of energy that can entirely replace fossil fuels starting in this decade.

While many researchers have been funded to study these processes on the scale of the sun and the solar system, work on larger scales has been hobbled by the straightjacket of the Big Bang hypothesis, which has diverted hundreds or thousands of talented researchers into futile calculations of the imaginary entities, such as dark matter and dark energy, that have been invented to prop up a failing theory. Open debate can clear away that failed theory and lead to the reorientation of cosmology to the study of real phenomena, advancing technology here on earth. It is time to end the censorship and to let the debate begin. Cosmology can emerge from its crisis once it is recognized that the Big Bang never happened.

stephan quintetmedium

Summary: Radio astronomy observations of Pulsars indicate that the Hubble Red Shift is caused by “Tired Light,” rather than the expansion of the universe.

When Hubble published his observations of red-shifted light from distant objects — there were two possible explanations that came to the fore. One, originated by Georges Lemaitre, was that the Universe was expanding. The other, from Fritz Zwicky, was that light lost energy as it traveled, termed “tired light”. At that time, ca. 1930, interstellar and intergalactic space were assumed to be perfect vacuums and thus there was no mechanism to redden the light. Now, 90 years later, we have actual observational evidence that Zwicky was right.

In the radio astronomy of Pulsars, we find that the shorter wavelengths of the leading edge of the pulse arrive before longer wavelengths. The velocity of light, c, is NOT constant, but rather varies by wavelength. This time dispersion is proportional to the distance from us of the pulsar, indicating that the reduction in velocity is cumulative. The observed effect is isotropic. The interstellar medium is not a vacuum but rather affects light waves in a way best described as having an Index of Refraction greater than 1, unity. We find the same phenomenon in the observation of Fast Radio Bursts from other galaxies, thus indicating that the intergalactic media is not an electromagnetic vacuum.

https://iai.tv/articles/the-big-bang-didnt-happen-auid-2215

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Earliest history of eukaryotic life: Integration of Biology and Geology

From time to time, GEITP ponders various aspects of the earliest evolution of Life Forms on Earth. The attached article discusses the early evolution of eukaryotes — which is arguably one of the most important processes in the history of life on Earth [see Box 1 of attached pdf.]. Eukaryotes, as a clade or lineage, are defined in terms of cellular complexity. This complexity enables morphological diversity in both unicellular and multicellular lineages — including animals, fungi, algae, and plants. Eukaryotes have also played a role in shaping the physical landscape and bio-geochemical cycles on Earth, ever since their origin in the early Proterozoic Era (i.e., 2,500 million years ago, all the way up to 541 million years ago).

Because the origin and early evolution of eukaryotes is so ancient, and many of the features that define the group are unlikely to be preserved in the geologic record — it has been challenging to uncover their early evolutionary history. Traditionally, our knowledge of the history of a major lineage such as the eukaryotes would rely heavily on the fossil record. While the fossil record of early eukaryotes is indeed vital to telling their story, it is also a relatively sparse and patchy source of information. Many fields — including genomics, phylogenetics, organic geochemistry, and redox geochemistry — have added new layers to our understanding of this ancient history. There are now convincing data for the origin of the eukaryote clade in the early Proterozoic and compelling data for diversification and increased ecological importance in the late Proterozoic, but there is much less consensus on events happening during the vast middle of this important interval. [“A picture is worth a thousand words,” and these figures and diagrams [see attached] are very helpful.]

It has been estimated that total-group eukaryotes [i.e., first eukaryotic common ancestor (FECA)] evolved between 1.6 and 3.0 billion years ago (BYA). Once established, LECA must have had at least a cytoskeleton, nucleus, and mitochondria to be “a eukaryote.” The vast majority of eukaryotes perform respiration with oxygen as the electron acceptor (and, while some can perform fermentation and other forms of anaerobic respiration, their metabolic pathways for generating energy are rudimentary, when compared with bacteria and archaea).

The original plastids (i.e., chloroplasts) derived from a subsequent endosymbiotic event with a cyanobacteria and became the center of oxygenic photosynthesis in eukaryotes. However, most photosynthetic eukaryotes are best described as mixotrophs because both respiration and photosynthesis play a major role in their metabolisms. Throughout their complex evolutionary history, plastids also became a driver for evolution and diversification in many other clades within the eukaryotes—via subsequent endosymbiotic events. Despite agreement on the overall story, there is still controversy over the actual partners involved as well as the timing and mechanisms of the primary symbiotic events.

The first agreed-upon eukaryote fossils have a complex cell wall, but no other preserved features; thus, it is unclear if they represent stem or crown groups (Figure I inside Box 1). The first crown-group eukaryote in the fossil record is an Archaeplastida, and thus a product of two endosymbiotic events, and a few evolutionary steps from LECA. It is possible, or even likely, that unclassifiable stem groups and recognizable crown groups coexisted in Proterozoic ecosystems.

If oxygen did not change significantly during the Proterozoic, then what other factors may have led to eukaryotic evolution, and emergence and diversification of crown groups, in the Neoproterozoic Era? Some suggest that intrinsic ecological changes, such as the rise of eukaryvory and predation, as drivers for Neoproterozoic diversification. Others have called on changes in nutrient fluxes, subtle changes in oxygenation levels that impacted nutrient levels, and even the breakup of the supercontinent Rodinia.

When did FECA and, subsequently, crown-group eukaryotes, evolve? The best evidence we have for crown-group eukaryotes are photosynthetic clades, which are more derived than the most basal eukaryotic lineages. Could basal heterotrophic crown group lineages be preserved in the geologic record? These ideas can be tested in part by recalibrating clocks using updated geochronology and collecting and incorporating new well-dated fossils.

The transition between FECA and crown group eukaryotes is an important evolutionary process that is likely rooted in major environmental transitions. What external environmental and/or paleoecological events may have triggered the origin of eukaryotes and subsequent diversification within the clade? There is compelling evidence for connections between abiotic factors and biological events recorded in the geologic record, however, it is difficult to infer causation between external environmental and evolutionary events; this can be explored via continued collection and integration of phylogenetic, geochemical, and fossil data.

Whatever the drivers, it is clear that total-group eukaryotes are present early in the Proterozoic, but do not leave a taxonomically definitive and biodiverse record until the end of the Proterozoic Era. Our analysis shows that sometimes biomarkers, molecular clocks, and fossils agree, and sometimes they do not. Yet it is only by delving into these apparent disagreements that we can refine our interpretations of the many proxies used in studying the early evolutionary history of eukaryotes. Further integration and synthesis will lead towards a more nuanced understanding of the early history of this overwhelmingly successful clade of life. 😊
DwN

COMMENT: Dan,
I would absolutely agree with that. John

COMMENT: John,
Wish I could’ve been there. And I would conclude that P450 genes had already arisen WELL BEFORE the Early Proterozoic Era (2.5 BYA). 😊
DwN

COMMENT: Indeed, most interesting. I spoke about this — and its implications for the evolving and transferring P450 genes, down through many millions of years of evolution, at the Cytochrome P450 meeting in Washington DC in July. Close to your own heart…

Trends in Ecology & Evolution, Mar 2022; 37: 3 https://doi.org/10.1016/j.tree.2021.11.005

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Did the US Jump the Gun with the New Omicron-Targeted Vaccines?

This article — just out today on Medscape — will no doubt be of interest to some of you.
DwN
Did the U.S. Jump the Gun with the New Omicron-Targeted Vaccines?

Céline Gounder and Elisabeth Rosenthal

September 12, 2022

Last month, the FDA authorized omicron-specific vaccines, accompanied by breathless science-by-press release and a media blitz. Just days after the FDA’s move, the Centers for Disease Control and Prevention followed, recommending updated boosters for anyone age 12 and up who had received at least two doses of the original covid vaccines. The message to a nation still struggling with the covid-19 pandemic: The cavalry — in the form of a shot — is coming over the hill.

But for those familiar with the business tactics of the pharmaceutical industry, that exuberant messaging — combined with the lack of completed studies — has caused considerable heartburn and raised an array of unanswered concerns.

The updated shots easily clear the “safe and effective” bar for government authorization. But in the real world, are the omicron-specific vaccines significantly more protective — and in what ways — than the original covid vaccines so many have already taken? If so, who would benefit most from the new shots? Since the federal government is purchasing these new vaccines — and many of the original, already purchased vaccines may never find their way into taxpayers’ arms — is the $3.2 billion price tag worth the unclear benefit? Especially when these funds had to be pulled from other covid response efforts, like testing and treatment.

Several members of the CDC advisory committee that voted 13-1 for the recommendation voiced similar questions and concerns, one saying she only “reluctantly” voted in the affirmative.

Some said they set aside their desire for more information and better data and voted yes out of fear of a potential winter covid surge. They expressed hope that the new vaccines — or at least the vaccination campaign that would accompany their rollout — would put a dent in the number of future cases, hospitalizations, and deaths.

That reasoning is, perhaps, understandable at a time when an average of more than 300 Americans are still dying of COVID each day.

But it leaves front-line health care providers in the impossible position of trying to advise individual patients whether and when to take the hot, new vaccines without complete data and in the face of marketing hype.

Don’t get us wrong. We’re grateful and amazed that Pfizer-BioNTech and Moderna (with assists from the National Institutes of Health and Operation Warp Speed) developed an effective vaccine in record time, freeing the nation from the deadliest phase of the COVID pandemic, when thousands were dying each day. The pandemic isn’t over, but the vaccines are largely credited for enabling most of America to return to a semblance of normalcy. We’re both up-to-date with our COVID vaccinations and don’t understand why anyone would choose not to be, playing Russian roulette with their health.

But as society moves into the next phase of the pandemic, the pharmaceutical industry may be moving into more familiar territory: developing products that may be a smidgen better than what came before, selling — sometimes overselling — their increased effectiveness in the absence of adequate controlled studies or published data, advertising them as desirable for all when only some stand to benefit significantly, and in all likelihood raising the price later.

This last point is concerning because the government no longer has funds to purchase covid vaccines after this autumn. Funding to cover the provider fees for vaccinations and community outreach to those who would most benefit from vaccination has already run out. So updated boosters now and in the future will likely go to the “worried well” who have good insurance rather than to those at highest risk for infection and progression to severe disease.

The FDA’s mandated task is merely to determine whether a new drug is safe and effective. However, the FDA could have requested more clinical vaccine effectiveness data from Pfizer and Moderna before authorizing their updated omicron BA.5 boosters.

Yet the FDA cannot weigh in on important follow-up questions: How much more effective are the updated boosters than vaccines already on the market? In which populations? And what increase in effectiveness is enough to merit an increase in price (a so-called cost-benefit analysis)? Other countries, such as the United Kingdom, perform such an analysis before allowing new medicines onto the market, to negotiate a fair national price.

The updated booster vaccine formulations are identical to the original COVID vaccines except for a tweak in the mRNA code to match the omicron BA.5 virus. Studies by Pfizer showed that its updated omicron BA.1 booster provides a 1.56 times higher increase in neutralizing antibody titers against the BA.1 virus as compared with a booster using its original vaccine. Moderna’s studies of its updated omicron BA.1 booster demonstrated very similar results. However, others predict that a 1.5 times higher antibody titer would yield only slight improvement in vaccine effectiveness against symptomatic illness and severe disease, with a bump of about 5% and 1% respectively. Pfizer and Moderna are just starting to study their updated omicron BA.5 boosters in human trials.

Though the studies of the updated omicron BA.5 boosters were conducted only in mice, the agency’s authorization is in line with precedent: The FDA clears updated flu shots for new strains each year without demanding human testing. But with flu vaccines, scientists have decades of experience and a better understanding of how increases in neutralizing antibody titers correlate with improvements in vaccine effectiveness. That’s not the case with COVID vaccines. And if mouse data were a good predictor of clinical effectiveness, we’d have an HIV vaccine by now.

As population immunity builds up through vaccination and infection, it’s unclear whether additional vaccine boosters, updated or not, would benefit all ages equally. In 2022, the U.S. has seen COVID hospitalization rates among people 65 and older increase relative to younger age groups. And while covid vaccine boosters seem to be cost-effective in the elderly, they may not be in younger populations. The CDC’s Advisory Committee on Immunization Practices considered limiting the updated boosters to people 50 and up, but eventually decided that doing so would be too complicated.

Unfortunately, history shows that — as with other pharmaceutical products — once a vaccine arrives and is accompanied by marketing, salesmanship trumps science: Many people with money and insurance will demand it whether data ultimately proves it is necessary for them individually or not.

We are all likely to encounter the SARS-CoV-2 virus again and again, and the virus will continue to mutate, giving rise to new variants year after year. In a country where significant portions of at-risk populations remain unvaccinated and unboosted, the fear of a winter surge is legitimate.

But will the widespread adoption of a vaccine — in this case yearly updated covid boosters — end up enhancing protection for those who really need it or just enhance drugmakers’ profits? And will it be money well spent?

The federal government has been paying a negotiated price of $15 to $19.50 a dose of mRNA vaccine under a purchasing agreement signed during the height of the pandemic. When those government agreements lapse, analysts expect the price to triple or quadruple, and perhaps even more for updated yearly covid boosters, which Moderna’s CEO said would evolve “like an iPhone.” To deploy these shots and these dollars wisely, a lot less hype and a lot more information might help.

COMMENT: Given the cost of severe illness — with mounting, repeated, undeniable evidence that vaccines reduce morbidity and mortality — it only makes sense to use all the tools we have. Vaccines are one of the greatest tools developed to fight disease.
I get an annual flu vaccine that is the best epidemiological guess as to which mutations and strains will be most prevalent and harmful each year. I don’t understand why people are so negative about a COVID booster.
Just my thoughts. K

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How can a temporal sequence of related memories — be explained — at the gene-environment level ?

Memories acquired close together in time often become linked, such that recalling one memory leads to the recall of additional memories. For example, recently while writing a “Memoirs” book for my children and grandkids, I tried to remember the name of my grade-school principal. First, I visualized the small white schoolhouse, then the faces and names of my (grades-1 through -8) grade school teachers, and then seeing the principal’s face in the hallway. After that, I recalled his last name (Thurman), after which I then could even remember his first name and curiously, even his middle initial (Wayne S.)! And then I recalled even a story he told students about serving in the U.S. Navy in the Pacific Theatre during WW2 and being on a burning battleship — as it returned to harbor..!! To recall that sequence of events in reverse order (i.e., going from the battleship to his last name to the white schoolhouse) probably could not have happened.

Real-world past memories seem to be formed in a particular sequence-framework and often are not acquired or recalled in isolation. Time is a key variable in the organization of memories, because events that are experienced close to one another in time are more likely to be meaningfully associated, whereas those that are experienced over a longer time interval are not. How does the brain segregate events that are temporally distinct?; the mechanism is not clear.

Authors [see attached article & editorial] show that, after the formation of a contextual memory, a delayed (12–24 h) increase — in expression of C-C chemokine receptor type-5 [(CCR5), an immune receptor that curiously is well known as a co-receptor for HIV infection!!] — determines the duration of the temporal window for associating or linking that memory with subsequent memories. How on earth did an immune-associated receptor get discovered to be a pivotal factor in a memory-sequence context of thoughts in the brain???

The delayed expression of CCR5 in mouse hippocampal dorsal CA1 neurons results in a decrease in neuronal excitability, which, in turn, negatively regulates neuronal memory allocation, thus decreasing the overlap between dorsal CA1 memory ensembles. Lowering this overlap affects the ability of one memory to trigger the recall of the other, and, therefore, closes the temporal window for memory linking. Authors also show that an age-related increase in the neuronal expression of CCR5, and its protein ligand C-C motif chemokine ligand-5 (CCL5) leads to impairments in memory linking in aged mice, which was shown to be reversed by using a Ccr5(-/-) knockout mouse — with, versus without, treatment by a drug thatis an inhibitor of the CCR5 receptor (this result should have clinical implications: think Alzheimer, other dementias). In summary, the data described in this study provide insights into the molecular and cellular mechanisms that shape the temporal window for memory linking, but also showing the interrelationship of the immune and central nervous systems.

What does this topic have to do with “gene-environment interactions?” Well, the environmental signal (in the example given above) is simply a question, posed as a thought: “What was my grade school principal’s name?” This thought stimulated neurons — in a subset of the central nervous system (CNS) grey matter — which resulted in a cascade of genetic networks leading to neuronal (electrical) activity in the form of a series of time-related memories. Subsequently, this sequence of memories led to the principal’s name, and even a WW2 story about him. The unanticipated surprise was the involvement of the immune system’s CCR5 and its ligand CCL5 in activating this CNS function. More generally, the exploration of brain activity during similar behaviors, but on more-granular or more-continuous timescales, will lead to a better understanding of how memories are organized into sequences, episodes and, ultimately, a chronology. 😊

DwN

Nature 2 Jun 2022; 606: 438-152 & News N Views pp 38-39.

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Researchers Discover a Possible Pathway to Prevent COVID Infection

These are worthwhile points, George. This study underscores the difficulties and complexities of transitioning — all the way from an in vitro system to a cell-culture system using Lec2 living cells — to studies in the intact laboratory animal, and, thereafter, into carefully planned clinical studies. ☹

DwN

COMMENT: The authors’ approach would involve competitive inhibition — which works best when the concentration of the therapeutic exceeds the concentration of the target.
For a successful approach, the therapeutic also should be “in place,” before viral exposure, and on all surface areas where the virus might land. This would be very difficult in the alveolar region, because of its size (roughly the area of a tennis court). Also, mucociliary clearance will be functioning to remove this proposed drug in an aerosol.
In the past, most antivirals work through other mechanisms. Nonetheless, this study’s approach represents “a candle in darkness.” 😊

G, Chair, Department of Environmental and Public Health
University of Cincinnati College of Medicine

From: Nebert, Daniel
Sent: Thursday, June 23, 2022 4:34 PM

Due to the large outpouring of interest among GEITP’ers in looking-at/reading/examining the preprint described in the previous email — attached please find the Petitjean et al., pdf file (from the David Alsteens Lab) in Nat Commun, in press, accepted for publication on 22 May 2022 (not 10th of May, as erroneously written below). ☹ 😊😊
DwN

Subject: Researchers Discover a Possible Pathway to Prevent COVID Infection

This brief article just appeared on Medscape, summarizing in layman’s terms a paper from Belgium that was published on 10 May 2022 in Nature Communications. The article is written very conservatively, succinctly, no hysteria or hype, and very honestly about the researchers’ plans next to test this experimental system in mice, and then, if successful, they would move on into clinical studies. This experimental approach to prevent SARS-CoV-2 infections — seems to be a reasonable, and a plausible concept to tackle all SARS-CoV-2 variants (current and future) — irrespective of any and all viral mutations. Therefore, it is believed to be worth sharing this news ASAP. 😊

DwN

Researchers Find a Pathway to Prevent COVID Infection

Sabine Verschelde and Frédéric Soumois

25 May 2022

BRUSSELS — The Catholic University of Louvain (UCLouvain) in Belgium announced that its researchers have managed to identify the key that allows the COVID-19 virus to attack cells. What’s more, they have succeeded in closing the lock to block the virus and prevent it from interacting with the cell, thereby preventing infection.

UCLouvain emphasized that this discovery, which was published in the scientific journal Nature Communications on May 10, is sparking hope that an aerosol antiviral therapy can be developed that would eradicate the virus in the case of an infection or a high-risk contact.

For 2 years, the team under David Alsteens, PhD, a researcher at the UCLouvain Institute of Biomolecular Science and Technology, has been working hard to understand the precise molecular mechanisms the virus uses to infect a cell. They investigated the interaction between sialic acids (SAs), a type of sugar residue that is located on the surface of cells, and the SARS-CoV-2 spike (S) protein to clarify its role in the infection process.

It was already known that the function of the sugar residues that coat the cells is to promote cell recognition, thus enabling, in particular, viruses to identify their targets more easily, but also to provide them with a point of attachment and to facilitate infection of the cells.

The researchers have now discovered a variant of these sugars that interacts more strongly with the S protein than other sugars do.

In other words, the university explained, “they found the set of keys that allows the virus to open the cell door.” So, the researchers decided to catch the virus in its own trap, by preventing it from attaching to its host cell. To do this, they blocked the S protein’s points of attachment, thus suppressing any interaction with the cell surface, as if a padlock had been placed on the lock on the cell’s entry door.

Th researchers added that the advantage of this discovery is that it acts on the virus, irrespective of mutations.

The team of researchers will now conduct tests on mice to apply this blocking of virus binding sites and observe whether it works on the body. The results should make it possible to develop a clinical antiviral therapy administered by aerosol in the case of infection or severely at-risk contact.

Posted in Center for Environmental Genetics | Comments Off on Researchers Discover a Possible Pathway to Prevent COVID Infection

Researchers Discover a Possible Pathway to Prevent COVID Infection

Due to the large interest among GEITP’ers in looking-at/reading/examining the preprint described in the previous email — attached please find the Petitjean et al., pdf file (from the David Alsteens Lab) in Nat Commun, in press, accepted for publication on 22 May 2022 (not 10th of May, as erroneously written below). 😊😊

DwN

This brief article just appeared on Medscape, summarizing in layman’s terms a paper from Belgium that was published on 10 May 2022 in Nature Communications. The article is written very conservatively, succinctly, no hysteria or hype, and very honestly about the researchers’ plans next to test this experimental system in mice, and then, if successful, they would move on into clinical studies. This experimental approach to prevent SARS-CoV-2 infections — seems to be a reasonable, and a plausible concept to tackle all SARS-CoV-2 variants (current and future) — irrespective of any and all viral mutations. Therefore, it is believed to be worth sharing this news ASAP. 😊

Researchers Find a Pathway to Prevent COVID Infection
Sabine Verschelde and Frédéric Soumois

25 May 2022

BRUSSELS — The Catholic University of Louvain (UCLouvain) in Belgium announced that its researchers have managed to identify the key that allows the COVID-19 virus to attack cells. What’s more, they have succeeded in closing the lock to block the virus and prevent it from interacting with the cell, thereby preventing infection.

UCLouvain emphasized that this discovery, which was published in the scientific journal Nature Communications on May 10, is sparking hope that an aerosol antiviral therapy can be developed that would eradicate the virus in the case of an infection or a high-risk contact.

For 2 years, the team under David Alsteens, PhD, a researcher at the UCLouvain Institute of Biomolecular Science and Technology, has been working hard to understand the precise molecular mechanisms the virus uses to infect a cell. They investigated the interaction between sialic acids (SAs), a type of sugar residue that is located on the surface of cells, and the SARS-CoV-2 spike (S) protein to clarify its role in the infection process.

It was already known that the function of the sugar residues that coat the cells is to promote cell recognition, thus enabling, in particular, viruses to identify their targets more easily, but also to provide them with a point of attachment and to facilitate infection of the cells.

The researchers have now discovered a variant of these sugars that interacts more strongly with the S protein than other sugars do.

In other words, the university explained, “they found the set of keys that allows the virus to open the cell door.” So, the researchers decided to catch the virus in its own trap, by preventing it from attaching to its host cell. To do this, they blocked the S protein’s points of attachment, thus suppressing any interaction with the cell surface, as if a padlock had been placed on the lock on the cell’s entry door.

Th researchers added that the advantage of this discovery is that it acts on the virus, irrespective of mutations.

The team of researchers will now conduct tests on mice to apply this blocking of virus binding sites and observe whether it works on the body. The results should make it possible to develop a clinical antiviral therapy administered by aerosol in the case of infection or severely at-risk contact.

Posted in Center for Environmental Genetics | Comments Off on Researchers Discover a Possible Pathway to Prevent COVID Infection