Superbug MRSA arose long before clinical use of antibiotics

 Scientists have found evidence that a type of the antibiotic resistant superbug MRSA arose in nature long before the use of antibiotics in humans and livestock, which has traditionally been blamed for its emergence.

Hedgehogs carry a fungus and a bacteria on their skin, and the two are locked in a battle for survival. The fungus secretes antibiotics to kill the bacteria, but in response the bacteria has evolved antibiotic resistance -- becoming Methicillin-resistant Staphylococcus aureus, or MRSA. Up to 60% of hedgehogs carry a type of MRSA called mecC-MRSA, which causes 1 in 200 of all MRSA infections in humans. Natural biological processes, not antibiotic use, drove the initial emergence of this superbug on hedgehogs around 200 years ago.

Staphylococcus aureus first developed resistance to the antibiotic methicillin around 200 years ago, according to a large international collaboration including the University of Cambridge, the Wellcome Sanger Institute, Denmark's Serum Statens Institut and the Royal Botanic Gardens, Kew, which has traced the genetic history of the bacteria.

They were investigating the surprising discovery -- from hedgehog surveys from Denmark and Sweden -- that up to 60% of hedgehogs carry a type of MRSA called mecC-MRSA. The new study also found high levels of MRSA in swabs taken from hedgehogs across their range in Europe and New Zealand.

The study is published today in the journal Nature.

The researchers believe that antibiotic resistance evolved in Staphylococcus aureus as an adaptation to having to exist side-by-side on the skin of hedgehogs with the fungus Trichophyton erinacei, which produces its own antibiotics.

The resulting methicillin-resistant Staphylococcus aureus is better known as the superbug MRSA. The discovery of this centuries-old antibiotic resistance predates antibiotic use in medical and agricultural settings.

"Using sequencing technology we have traced the genes that give mecC-MRSA its antibiotic resistance all the way back to their first appearance, and found they were around in the nineteenth century," said Dr Ewan Harrison, a researcher at the Wellcome Sanger Institute and University of Cambridge and a senior author of the study.

He added: "Our study suggests that it wasn't the use of penicillin that drove the initial emergence of MRSA, it was a natural biological process. We think MRSA evolved in a battle for survival on the skin of hedgehogs, and subsequently spread to livestock and humans through direct contact."

Antibiotic resistance in bugs causing human infections was previously thought to be a modern phenomenon, driven by the clinical use of antibiotics. Misuse of antibiotics is now accelerating the process, and antibiotic resistance is rising to dangerously high levels in all parts of the world.

Since almost all the antibiotics we use today arose in nature, the researchers say it is likely that resistance to them already exists in nature too. Overuse of any antibiotic in humans or livestock will favour resistant strains of the bug, so it is only a matter of time before the antibiotic starts to lose its effectiveness.

"This study is a stark warning that when we use antibiotics, we have to use them with care. There's a very big wildlife 'reservoir' where antibiotic-resistant bacteria can survive -- and from there it's a short step for them to be picked up by livestock, and then to infect humans," said Professor Mark Holmes, a researcher in the University of Cambridge's Department of Veterinary Medicine and a senior author of the report.

In 2011, previous work led by Professor Holmes first identified mecC -MRSA in human and dairy cow populations. At the time it was assumed the strain had arisen in the cows because of the large amount of antibiotics they are routinely given.

MRSA was first identified in patients in 1960, and around 1 in 200 of all MRSA infections are caused by mecC-MRSA. Due to its resistance to antibiotics, MRSA is much harder to treat than other bacterial infections. The World Health Organization now considers MRSA one of the world's greatest threats to human health. It is also a major challenge in livestock farming.

The findings are not a reason to fear hedgehogs, say the researchers: humans rarely get infections with mecC-MRSA, even though it has been present in hedgehogs for more than 200 years.

"It isn't just hedgehogs that harbour antibiotic-resistant bacteria -- all wildlife carries many different types of bacteria, as well as parasites, fungi and viruses," said Holmes.

He added: "Wild animals, livestock and humans are all interconnected: we all share one ecosystem. It isn't possible to understand the evolution of antibiotic resistance unless you look at the whole system."

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Story Source:

Materials provided by University of Cambridge. The original text of this story is licensed under a Creative Commons License. Note: Content may be edited for style and length.

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Journal Reference:

1. Jesper Larsen, Claire L. Raisen, Xiaoliang Ba, Nicholas J. Sadgrove, Guillermo F. Padilla-González, Monique S. J. Simmonds, Igor Loncaric, Heidrun Kerschner, Petra Apfalter, Rainer Hartl, Ariane Deplano, Stien Vandendriessche, Barbora Černá Bolfíková, Pavel Hulva, Maiken C. Arendrup, Rasmus K. Hare, Céline Barnadas, Marc Stegger, Raphael N. Sieber, Robert L. Skov, Andreas Petersen, Øystein Angen, Sophie L. Rasmussen, Carmen Espinosa-Gongora, Frank M. Aarestrup, Laura J. Lindholm, Suvi M. Nykäsenoja, Frederic Laurent, Karsten Becker, Birgit Walther, Corinna Kehrenberg, Christiane Cuny, Franziska Layer, Guido Werner, Wolfgang Witte, Ivonne Stamm, Paolo Moroni, Hannah J. Jørgensen, Hermínia de Lencastre, Emilia Cercenado, Fernando García-Garrote, Stefan Börjesson, Sara Hæggman, Vincent Perreten, Christopher J. Teale, Andrew S. Waller, Bruno Pichon, Martin D. Curran, Matthew J. Ellington, John J. Welch, Sharon J. Peacock, David J. Seilly, Fiona J. E. Morgan, Julian Parkhill, Nazreen F. Hadjirin, Jodi A. Lindsay, Matthew T. G. Holden, Giles F. Edwards, Geoffrey Foster, Gavin K. Paterson, Xavier Didelot, Mark A. Holmes, Ewan M. Harrison, Anders R. Larsen. Emergence of methicillin resistance predates the clinical use of antibiotics. Nature, 2022; DOI: 10.1038/s41586-021-04265-w

https://www.sciencedaily.com/releases/2022/01/220105111403.htm

How LPS prevents or promotes development of asthma and allergic disease by airborne allergens

 Immunologists have long been baffled by LPS, the bacterial lipopolysaccharide that helps form the cell walls of Gram-negative bacteria.

Many experiments show that exposure to LPS during exposure to environmental allergens protects against developing asthma or allergic disease. Yet other numerous experiments show that the presence of LPS during exposure to environmental allergens does the opposite -- it promotes the development of asthma and other allergic disease.

Now Beatriz León, Ph.D., and fellow University of Alabama at Birmingham researchers have cut this Gordian knot in a study published in Cell Reports. They detail a series of mechanistic steps that reveal a surprising answer -- the key to LPS' promoting or preventing the allergic reaction lies in the allergen itself.

Greater understanding of the mechanisms underlying sensitization to allergic disease can offer new strategies to control allergic airway disease, especially asthma. A global epidemic of asthma, including a sharp increase in developed countries since the 1960s, affects about 300 million children and adults worldwide.

León and her UAB colleagues unraveled a complex trail for the antagonistic mechanisms of LPS to promote or prevent allergic disease through activation or suppression of T helper-2 immune cells.

Here are their findings, which also define specific roles for immune cells called classical monocytes and non-classical monocytes.

First, the presence of cysteine protease enzymatic activity in an airborne allergen is required for bacterial LPS to have its protective effect. Allergens that contain cysteine protease enzymatic activity -- like house dust mites or papain, an enzyme from papayas -- lead to prevention of sensitization in the presence of LPS. In contrast, the German cockroach airborne allergen, which lacks cysteine protease activity, promotes sensitization, despite the presence of LPS.

The cysteine protease acts through a still unknown mechanism to induce non-classical monocytes in the lungs to produce the cytokine GM-CSF, or granulocyte-macrophage colony-stimulating factor. GM-CSF signaling governs the ability of LPS to suppress T helper-2 responses to allergens like house dust mites.

"Consequently, because the protective effects of LPS depend on GM-CSF, the beneficial effects of LPS are restricted to allergens that have cysteine protease activity," León said.

In the absence of GM-CSF, LPS can favor pathogenic T helper-2 cell responses by supporting the trafficking of lung migratory dendritic cells into the lung-draining lymph nodes, where they can help initiate an immune response. However, when non-classical monocytes produce GM-CSF, LPS and GM-CSF synergize to differentiate classical monocytes into monocyte-derived dendritic cells that instruct the lung migratory dendritic cells for the suppression of T helper-2 cell allergic airway inflammation, through the production of interleukin-12.

"Our results show that GM-CSF segregates the opposed functions LPS has in the priming of allergen-specific T helper-2 cell responses," León said. "Different host sensitivities to GM-CSF and/or LPS -- influenced by genetic diversity or by environmental factors -- can therefore significantly affect the risk of allergic sensitization. Understanding these interactions may provide insight into future therapeutic interventions to circumvent and even reverse allergic disease."

The study, "GM-CSF production by non-classical monocytes controls antagonistic LPS-driven functions in allergic inflammation," involved different allergen sensitization in mouse models, transcriptional analysis, and in vivo loss-of-function and gain-of-function experiments.

Support came from National Institutes of Health grants AI116584 and AI150664, and from UAB. Microbiology and Medicine are departments in the UAB Marnix E. Heersink School of Medicine.

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Story Source:

Materials provided by University of Alabama at Birmingham. Original written by Jeff Hansen. Note: Content may be edited for style and length.

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Journal Reference:

1. Kamaljeet Kaur, Holly Bachus, Crystal Lewis, Amber M. Papillion, Alexander F. Rosenberg, André Ballesteros-Tato, Beatriz León. GM-CSF production by non-classical monocytes controls antagonistic LPS-driven functions in allergic inflammation. Cell Reports, 2021; 37 (13): 110178 DOI: 10.1016/j.celrep.2021.110178

https://www.sciencedaily.com/releases/2022/01/220105122352.htm

Walmart halves paid leave for COVID-positive workers

 Walmart Inc workers in the United States who must isolate or who have tested positive for COVID-19 will receive one week of paid leave instead of two under a new policy that aligns with a change in U.S. health guidance.

A memo, seen by Reuters, sent on Tuesday to U.S. hourly store employees and long-haul drivers said COVID-19 positive workers and those required to quarantine - by Walmart, a health care provider or a government agency - are eligible for one work week of paid time off.

The company's guidelines follow the U.S. Centers for Disease Control and Prevention's updated recommendations last week that people isolate for five days after a COVID-19 infection, instead of 10 days.

The retailer, the largest private employer in the United States with about 1.6 million workers, is among the first major retailers to reduce paid leave for COVID-19, and could serve as a bellwether for other major employers.

The move comes as a spike in COVID-19 cases is causing significant labor shortages across an industry that is already battling supply-chain snarls, product shortages, rising inflation and rocketing transportation costs.

A Walmart spokesperson confirmed the COVID-leave policy change. Workers who continue to be sick can potentially receive additional COVID-related pay for up to 26 weeks.

The spokesperson added that Walmart was asking corporate employees to work primarily from home until Jan. 30, rather than Jan. 10 previously announced.

The company operates 600 Sam's Club stores and more than 4,700 Walmart U.S. stores in the United States. On Monday, the company said it temporarily shut 60 stores in COVID-19 hot spots in December to sanitize them against the virus.

"A lot of people don't want to come into work as they're either afraid or getting coronavirus," Peter Naughton, 46, a Walmart electronics salesperson in Baton Rouge and member of labor non-profit United for Respect. "I can't afford not to come to work."

Like other mass retailers, Walmart has witnessed a boom in sales during the pandemic as more people shopped for groceries and home goods. The company raised its full-year annual sales and profit forecast in November but disappointed investors with higher labor and transportation costs that eroded margins.

The company's stock is nearly flat over the past one year compared to the broader S&P 500 retailing index's 20.6% rise over the same period.

https://www.marketscreener.com/news/latest/Walmart-halves-paid-leave-for-COVID-positive-workers--37474542/

Chase Bank shuts dozens of NYC branches due to Omicron

 Chase Bank has shuttered more than three dozen branches in the Big Apple as the mega-bank struggles with staff shortages and vaccine mandates amid a surge in Omicron.

While the COVID variant has shelved many JP Morgan Chase employees, at least one local pol blamed the bank closures on “prohibitive” city and state mandates that require private-sector workers to be vaccinated before they can show up for a day at the office.

“It doesn’t give business an opportunity to open the front door,” City Councilman Joe Borelli, a Staten Island Republican, told The Post.

“If we want to re-populate our offices in New York, this mandate is a prohibition on many of those people coming back,” Borelli said.

Borelli also took to Twitter Wednesday to make his point, posting a photo of the laminated signs that adorn many closed branches.

“I don’t think the mandates are working in #nyc,” he wrote.

“Our branch is temporarily closed due to New York City’s COVID-19 Workplace Vaccination Order,” the sign on the door of one branch reads.

Councilman Joe Borelli blamed the staffing issues on the city’s and state’s vaccine mandate.

William Farrington

Recently departed Mayor Bill de Blasio announced the vaccine mandate last year, with the measure going into effect on Dec. 27 — just days before the end of his term.

Mayor Eric Adams said just hours into his first term that he would continue de Blasio’s emergency measures, including indoor vaccine mandates.

A spokesman for JP Morgan Chase said Wednesday that “a small portion” of the financial giant’s locations in the five boroughs would close due to the vaccine mandate and said some branches in the New York Metro area also had staff shortages.

But, Chase Vice President of Regional Communications Briana Curran added that, “If they are closed in NYC it is due to the vaccine mandate.”

Curran would not provide a list of all the local shuttered branches, but a survey of branch locations listed on Chase’s website show that at least 11 of 37 Bronx locations are currently closed, as are at least 21 of 67 Brooklyn branches.

Two of nine Staten Island sites are also closed.

Some are blaming the city’s vaccine mandate on the closures.

Getty Images

Chase announced on Dec. 14 that employees at its corporate offices would be prohibited from going into the building unless they were vaccinated.

The mandate has nonetheless sparked blowback from the city’s business community.

This week, a Staten Island law firm filed a federal class-action lawsuit seeking an injunction on the mandate targeting private businesses, calling it “overreaching and meddling” into the private sector.

Mark Fonte, an attorney with F&G Legal Group, told The Post Wednesday that more than 100 companies in the five boroughs had already joined the lawsuit.

“This is seeking to put the government back in its place and keep it in its proper lane, out of the offices of private businesses,” Fonte said.

JP Morgan Chase is not one of those companies, he noted.

https://nypost.com/2022/01/05/chase-bank-shuts-dozens-of-nyc-branches-due-to-omicron/

NYC hospitals to get nearly $140 million funding boost during Omicron surge

 Big Apple hospitals will receive nearly $140 million in funding as they grapple with a surge of COVID-19 hospitalizations from the highly contagious Omicron variant, officials announced Wednesday. 

The city’s public hospital system, NYC Health + Hospitals, will receive an extra $111 million in support from City Hall and smaller, private safety-net hospitals will get $27 million in loans from Goldman Sachs. 

“Our hospitals are under some degree of strain right now, compounded by the staff outages because of COVID infections related to Omicron,” Dave Chokshi, the city’s Commissioner of Health, said during a press conference at Elmhurst Hospital, which was famously hard hit during the early days of the pandemic last spring. 

“Cases are increasing and hospitalizations are increasing, I expect that will continue in the near-term.” 

The $111 million in funding to H+H will be used to hire more nurses and support staff, and the loans for private hospitals will give them the liquidity they need to stay afloat amid the surge. The repayment terms for the loans weren’t immediately made clear but the funds could be reimbursed by FEMA down the line. 

Hospitalizations rates for COVID-19 in the five boroughs are the highest seen since May 2020 and are up more than 50 percent this week compared to the same time period in 2021 when the vaccine was just starting to be distributed, state data show.

Across the city, hospital beds are about 75 to 80 percent full, and a peak in cases isn’t expected for another two to three weeks, Chokshi said. 

Dave Chokshi said NYC hospitals are facing a “strain” with the latest surge.

AP

“What we are looking for is a deceleration in the rate of growth … we’re not seeing that yet,” Chokshi said. 

“We are seeing some leveling off of that just in recent days, it’s a little bit too early to tell whether that’s just due to holiday testing patterns or a real leveling off.”

When asked if the hospitalization numbers are misleading and if they include people who were hospitalized for other reasons, and also happened to test positive for COVID-19, Chokshi responded: “The short answer is no.” 

Even as hospitalizations in NYC increase, experts say that the peak for Omicron cases has not quite happened yet.

Wang Ying / Xinhua News Agency via Getty Images

“I don’t think that we’re scaring New Yorkers in terms of what we’re conveying. We do have to look at all the data together. We have seen a steep increase in COVID hospitalizations,” he said. 

Nationwide, hospital admissions are down 50 percent compared to last year’s surge, even as new coronavirus cases tripled in the past few weeks, data from the Centers for Disease Control and Prevention show.

https://nypost.com/2022/01/05/nyc-hospitals-to-get-140-million-funding-boost-during-omicron-surge/

Pawp, easy way to talk to a vet online

 If we learned anything from the past two years, it’s that telehealth is the wave of the future. That said, if a doctor can check our vitals via Zoom, our pets deserve the same love, affection and care online, too.

Yes, this exists, and we honor Pawp for making the process of instantly talking to a vet as simple and streamlined as can be.

The service, which redefines care for all cats and dogs, relays unlimited 24/7 veterinarian-to-patient care via text and video with experienced medical professionals at the top of their fields. And, it’ll help answer any question about your pet, from injuries and throwing up to behavior and nutrition-related inquiries anywhere, anytime.

Plus, there are no wait times or appointments required, so you’ll have all your questions answered within a couple of minutes.

The brand is quite extraordinary, with a direct-to-consumer platform (and now an iOs app) that breeds on saving you money in the long run — pun absolutely intended.

Pawp — The Digital Clinic for Pets, $24 per month

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You can save money with Pawp

We don’t have to tell you twice; visits to the vet can add up. To put an exact number on it, an emergency visit to the vet can range from $250 to $8,000, according to Pawp’s website.

This holds true if you have a number of pets in your home, too. Have no fear, Pawp will cover up to six pets on your plan at no extra cost, even those with pre-existing health conditions.

Just as conveniently, there are no out-of-pocket costs since Pawp pays the vet directly before you leave the clinic. As mentioned, Pawp’s team of qualified vets is there to assist you 24/7 with its digital clinic.

Pawp understands the importance of making pet care accessible

Remarkably, there are approximately 164 million cats and dogs in the U.S., yet the market penetration for pet insurance is only 2.8%. That’s only three dogs out of 100 and not even one cat. The reason? Pet insurance can be expensive, which is why Pawp is the best alternative for pet owners.

Instead of paying a premium (which averages $42.45 for dogs and $20.99 for cats per month), Pawp covers one emergency a year, even if the SOS situation is related to a preexisting health condition. That’s pretty amazing, considering no other pet insurance providers cover pre-existing conditions.

Pawp acts as your safety net for emergency vet bills, thanks to the Pawp Emergency Fund. For $24 a month — or $288 a year — you get $3,000 annually for one of your pet’s emergencies. This way, you’ll be able to afford those impromptu, inevitable moments that come with being a pet owner.

You can use your Emergency Fund at any vet in the U.S., too.

Pawp is one of the easiest pet care platforms to use

Aside from around-the-clock service administered by well-trained veterinarians, you’ll have access to unlimited video calls and texts with no appointments or wait times — it’s just that simple.

Plus, with your pet’s profile, your vet will have all the basic-level information they need, like breed, age and weight.

https://nypost.com/2022/01/05/pawp-the-easiest-way-to-talk-to-a-vet-online/

What Spooked Markets So Badly In Today's Fed Minutes? JPMorgan, Goldman Explain

 Considering that today's minutes covered a FOMC meeting that took place some three weeks ago, with numerous Fed speakers having ample opportunity to set the stage for what was to come (talk about those famous Fed "communication" skills), it is rather shocking how powerful and violent today's stock tantrum was.

But what exactly spooked traders so badly?

Well, as JPM Michael Feroli writes in his FOMC post-mortem, the minutes portray "a Committee on the march toward removing policy accommodation" which is not a surprise to anyone except perhaps the biggest cubic zirconium hands out in Seoul. Regarding the expected path of policy rates the minutes note that meeting participants generally see rate hikes “sooner or at a faster pace" than previously expected. Of course, this too had already been hinted at by the dots released after the meeting.

What was new in these minutes, and was also unexpectedly hawkish, were the clues given to how balance sheet normalization would play out. While most favored allowing assets to run off after the first rate hike, it was generally thought that this runoff would occur sooner after liftoff relative to the 2014-17 episode. Moreover, it was generally felt that the pace of runoff would be faster than the last experience: as a reminder, last time it took two years between the first rate hike and the beginning of balance-sheet contraction (see excerpt below) so the Fed is now hinting that it could shorten this to less than nine months so that runoff begins in 2022... or at least that's how the market reads it.

And the other big surprise is that some on the Committee felt that tightening financial conditions by relying more on balance sheet runoff and less on rate hikes would help steepen the curve, a desirable outcome in their opinion, though it’s not clear this was a widely-shared view, especially considering the catastrophic conclusion to the Fed's tapering in Sept 2019 when JPMorgan had to crash to repo market to force the Fed to launch Not QE (narrator: it was QE) when the financial system promptly ran out of reserves. Here is the section in question:

Some participants commented that removing policy accommodation by relying more on balance sheet reduction and less on increases in the policy rate could help limit yield curve flattening during policy normalization. A few of these participants raised concerns that a relatively flat yield curve could adversely affect interest margins for some financial intermediaries, which may raise financial stability risks. However, a couple of other participants referenced staff analysis and previous experience in noting that many factors can affect longer-dated yields, making it difficult to judge how a different policy mix would affect the shape of the yield curve.

Many participants judged that the appropriate pace of balance sheet runoff would likely be faster than it was during the previous normalization episode. Many participants also judged that monthly caps on the runoff of securities could help ensure that the pace of runoff would be measured and predictable, particularly given the shorter weighted average maturity of the Federal Reserve's Treasury security holdings.

Separately, Feroli also notes that "many" also felt the recently-authorized standing repo facility should support faster and smoother balance sheet normalization, and as has been the case recently, “some” participants favored a quicker runoff pace for agency MBS relative to US Treasuries.

There were fewer surprises regarding the Fed's views on the economy where the staff revised up their inflation forecast for coming years, noting the “salience” of ’21 inflation outcomes. On the labor market, some on the Committee noted that the recovery was already “more inclusive.” In the discussion of the labor force participation rate, the Committee sounded more pessimistic that participation would soon recover, if ever. More generally, “several” thought the labor market was already at maximum employment, and many others thought it would “fast approach” that criterion. It was also noted by “some” participants that liftoff could happen before maximum employment had been reached if inflation expectations appeared to become unanchored.

Commenting on the maximum employment assessment, Bloomberg economist Yelene Shulyatyeba said that “the FOMC participants’ labor-market assessment suggests they see the economy at or very close to full employment. Apart from ‘a number of signs that the U.S. labor market was very tight,’ policy makers also saw little potential for a significant short-term improvement in participation. Therefore, the economy may have achieved full employment earlier and with a smaller labor force than previously foreseen, which implies the need for tighter policy sooner than anticipated.”

We disagree with this for reasons we explained in "A March Rate Hike? Not So Fast"

Finally, while virus variant risks were noted several times, the overall tone of the minutes suggests this was not expected to be a major headwind to the growth outlook.

Shifting from JPM to Goldman's post-mortem, the bank's Jan Hatzius cut to the chase and titled his note with the big punchline. namely that "Fed Balance Sheet Runoff Could Start “Relatively Soon” After Liftoff." Similar to Feroli, this is how he explains it:

The December FOMC minutes indicated that participants continued to view mid-March as an appropriate end date for net asset purchases. The minutes also noted that “some” participants said that it could be appropriate to start runoff “relatively soon after beginning to raise the federal funds rate” and “many” participants judged that the appropriate pace of balance sheet runoff would likely be faster than last cycle. 

In our view, today’s minutes increase the chances that the FOMC might be ready to reach a decision on the runoff process and issue new normalization principles in the second quarter, which could mean that runoff begins somewhat earlier than our standing assumption of Q4.  We still expect that the start of runoff will substitute for a quarterly hike, so that the FOMC would still hike 3 times total in 2022 if runoff begins in Q3, but an earlier announcement of the start of runoff would be somewhat less likely to substitute for a hike than one that comes toward the end of the year.

This is all fine and good, and it is certainly far more hawkish than the market expected, but it does raise several questions, as today's market action indicated.

First, and foremost, back in 2018 when r-star was far higher than it is today, the Fed managed to get away with 8 rate hikes before a 20% drop in stocks forced Powell into a premature easing cycle in the summer of 2019, right around the time the repo crisis emerged and the Fed realized it needs to add far more reserves (and lo and behold 7 months later, we got just the perfect Made in China excuse to inject trillions into the financial system). So the first question is how many rate hikes can the Fed get away with now that global debt is orders of magnitude higher than it was just 4 years ago. 3 hikes? 4 hikes and a run off, before the next big crash forces the Fed into early easing.

Keep a close eye on fwd OIS swaps markets for the tell on when the next rate cut cycle/QE will start.

And tied to that are two more question: while it is clear that Biden is freaking out about inflation far more than he is about the prospect of a market crash, is the president even remotely aware of what a 20%, 30% (or more) crash in the market will do to Democrats in the polls, and midterms, not to mention 2024? Something tells us the answer is no.

Last but not least is the question everyone would like answered: just how is the Fed tightening financial conditions going to ease a historic supply chain collapse which is driven by countless other factors than just excess demand sparked by Biden's stimmies.

We doubt we will find out the answer, but we also doubt that the market's latest freak out about much tighter financial conditions - including 3 rate hikes and balance sheet run off starting in 2022 - will ever come to pass. Because if it does, the only question then is how long before the Fed starts monetizing ETFs, cryptos and NFTs to preserve the $145 trillion or so in US net worth parked squarely in the hands of the 1%, the only legacy the US central bank will leave on this earth.

https://www.zerohedge.com/markets/what-spooked-markets-so-badly-todays-fed-minutes-jpmorgan-goldman-explain