'Pre-surgical antibody treatment might prevent heart transplant rejection'

 A new study from scientists at Cincinnati Children's suggests there may be a way to further protect transplanted hearts from rejection by preparing the donor organ and the recipient with an anti-inflammatory antibody treatment before surgery occurs.

The findings, published online in the Proceedings of the National Academy of Sciences, focus on blocking an innate immune response that normally occurs in response to microbial infections. The same response has been shown to drive dangerous inflammation in transplanted hearts.

In the new study—in mice—transplanted hearts functioned for longer periods when the organ recipients also received the novel antibody treatment. Now the first of a complex series of steps has begun to determine whether a similar approach can be safely performed for human heart transplants.

"The anti-rejection regimens currently in use are broad immunosuppressive agents that make the patients susceptible to infections. By using specific antibodies, we think we can just block the inflammation that leads to rejection but leave anti-microbial immunity intact," says corresponding author Chandrashekhar Pasare, DVM, Ph.D., director of the Division of Immunobiology at Cincinnati Children's.

Making memory T cells a bit more forgetful

The research team, which included first author Irene Saha, Ph.D., a research fellow in the Pasare Lab, and several colleagues at Cincinnati Children's, zeroed in on how dendritic cells from the donor organ trigger an inflammatory response in the recipient's body.

Specifically, the team found that memory CD4 T cells in the recipient activated donor dendritic cells through signals delivered by the proteins CD40L and TNFα. When this signaling pathway was blocked with gene editing techniques, the results included dampened inflammation and prolonged survival of transplanted hearts.

In the study, untreated mice rejected the donated heart within a week. But in mice that were gene edited to lack receptors for CD40L and TNFα, strong heart function persisted through day 66, when the experiment was terminated.

"We have been working on this for almost a decade," Pasare says. "The major reason we figured out this pathway is because we focused on understanding how memory T cells in the recipient with potential reactivity to donor specific antigens induce innate inflammation.

"The rest of the field has focused on other concepts such as ischemia reperfusion injury, ligands from dead cells, and innate immune receptors, none of which seem to really lead to transplant rejection.

"The key to preventing organ rejection is to take away the ability of recipient's memory T cells to initiate inflammation when they recognize donor antigens in dendritic cells. While T cell memory is critical to fight infections, the innate inflammation initiated by memory T cells is detrimental to the survival of transplanted organs."

Next steps

The co-authors believe the process they used to protect hearts from rejection may also apply to other forms of organ transplantation.

However, the gene editing performed with the mice would not be considered safe for humans. So now the research team is evaluating other ways to disrupt the inflammatory response.

"Using blocking antibodies against CD40 could be a good approach. Another option would be to create biologics or compounds that specifically target the TNF receptor superfamily in humans," Pasare says. "I think this is a very exciting area for future drug development."

More information: Pasare, Chandrashekhar, Alloreactive memory CD4 T cells promote transplant rejection by engaging DCs to induce innate inflammation and CD8 T cell priming, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2401658121

https://medicalxpress.com/news/2024-08-pre-surgical-antibody-treatment-heart.html

Fauci Infected With COVID 3rd Time After Being "Vaccinated And Boosted 6 Times"

 by Paul Joseph Watson via Modernity.news,

Dr. Anthony Fauci revealed that he’s been infected with COVID for a third time despite having been “vaccinated and boosted six times.”

Yes, really.

The former chief medical advisor to the president, who became the face of the COVID vaccination drive from late 2020 onwards, reacted to catching COVID-19 yet again by thanking the vaccine.

“I got infected about two weeks ago, it was my third infection, and I have been vaccinated and boosted a total of six times,” said Fauci.

Fauci, who back in 2021 said, “If you get vaccinated, you are protected,” seemingly hasn’t been protected from catching the virus despite receiving half a dozen vaccines.

He also separately asserted during the same year, “When people get vaccinated, they can feel safe that they are not gonna get infected.”

Those comments have aged rather badly.

Respondents on X had a field day.

*  *  *

https://www.zerohedge.com/covid-19/dr-fauci-admits-hes-infected-covid-third-time-after-being-vaccinated-and-boosted-six-times

'Cognitive Breakdown: The New Memory Condition Primary Care Needs to Know'

['[A] buildup of deposits of the TAR DNA-binding protein 43 (TDP-43) protein'--sound familiar from somewhere else?]

 

Patients experiencing memory problems often come to neurologist David Jones, MD, for second opinions. They repeat questions and sometimes misplace items. Their primary care clinician has suggested they may have Alzheimer's disease or something else.

In many cases, Jones, a neurologist with Mayo Clinic in Rochester, Minnesota, performs a series of investigations and finds the patient instead has a different type of neurodegenerative syndrome, one that progresses slowly, seems limited chiefly to loss of memory, and which tests show affects only the limbic system.

The news of diagnosis can be reassuring to patients.

"Memory problems are not always Alzheimer's disease," Jones told Medscape Medical News. "It's important to broaden the differential diagnosis and seek diagnostic clarity and precision for patients who experience problems with brain functioning later in life."

Jones and his colleagues recently published clinical criteria for what they call limbic-predominant amnestic neurodegenerative syndrome (LANS).

Various underlying etiologies are known to cause degeneration of the limbic system, the most frequent being a buildup of deposits of the TAR DNA-binding protein 43 (TDP-43) protein referred to as limbic-predominant, age-related TDP-43 encephalopathy neuropathological change (LATE-NC). LATE-NC first involves the amygdala, followed by the hippocampus, and then the middle frontal gyrus, and is found in about 40% of autopsied brains in people over age of 85 years.

By contrast, amnestic syndromes originating from neocortical degeneration are largely caused by neuropathological changes from Alzheimer's disease and often present with non-memory features.

Criteria for LANS

Broken down into core, standard, and advanced features

• Core clinical features:

The patient must present with a slow, amnestic, predominant neurodegenerative syndrome — an insidious onset with gradual progression over 2 or more years — without another condition that better accounts for the clinical deficits.

• Standard supportive features:

1. Older age at evaluation.

   Most patients are at least the age of 75 years. Older age increases the likelihood that the amnestic syndrome is caused by degeneration of the limbic system.

2. Mild clinical syndrome.

   A diagnosis of mild cognitive impairment or mild amnestic dementia (ie, a score of ≤ 4 on the Clinical Dementia Rating Sum of Boxes [CDR-SB]) at the first visit.

3. Hippocampal atrophy out of proportion to syndrome severity.

   Hippocampal volume was smaller than expected on MRI compared with the CDR-SB score.

4. Mildly impaired semantic memory.

• Advanced supportive features:

1. Limbic hypometabolism and absence of neocortical degenerative pattern on fludeoxyglucose-18-PET imaging.
2. Low likelihood of significant neocortical tau pathology.

Jones and his colleagues also classified a degree of certainty for LANS to use when making a diagnosis. Those with the highest likelihood meet all core, standard, and advanced features.

Patients with a high likelihood of having LANS meet core features, at least three standard features and one advanced feature; or meet core features, at least two standard features as well as two advanced features. Those with a moderate likelihood meet core features and at least three standard features or meet core features and at least two standard features and one advanced feature. Those with a low likelihood of LANS meet core features and two or fewer standard features.

To develop these criteria, the group screened 218 autopsied patients participating in databases for the Mayo Clinic Study of Aging and the multicenter Alzheimer's Disease Neuroimaging Initiative. They conducted neuropathological assessments, reviewed MRI and PET scans of the brains, and studied fluid biomarkers from samples of cerebrospinal fluid.

In LANS, the neocortex exhibits normal function, Jones said. High-level language functions, visual spatial functions, and executive function are preserved, he said, and the disease stays mild for many years. LANS is highly associated with LATE, for which no biomarkers are yet available.

The National Institute on Aging in May 2023 held a workshop on LATE, and a consensus group was formed to publish criteria to help with the diagnosis. Many LANS criteria likely will be in that publication as well, Jones said.

Several steps lay ahead to improve the definition of LANS, the authors wrote, including conducting prospective studies and developing clinical tools that are sensitive and specific to its cognitive features. The development of in vivo diagnostic markers of TDP-43 pathology is needed to embed LANS into a disease state driven by LATE-NC, according to Jones' group. Because LANS is newly defined, clinical trials are needed to determine the best treatments, he said.

"We are increasingly recognizing that the syndrome of dementia in older adults is heterogeneous," said Sudha Seshadri, MD, DM, a behavioral neurologist and founding director of the Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases at the University of Texas Health Science Center at San Antonio, San Antonio.

LANS "is something that needs to be diagnosed early but also needs to be worked up in a nuanced manner, with assessment of the pattern of cognitive deficits, the pattern of brain shrinkage on MRI, and also how the disease progresses over, say, a year," said Seshadri. "We need to have both some primary care physicians and geriatricians who are comfortable doing this kind of nuanced advising and others who may refer patients to behavioral neurologists, geriatricians, or psychiatrists who have that kind of expertise."

About 10% of people presenting to dementia clinics potentially could fit the LANS definition, Seshadri said. Seshadri was not a coauthor of the classification article but sees patients in the clinic who fit this description.

"It may be that as we start more freely giving the diagnosis of a possible LANS, the proportion of people will go up," Seshadri said.

Primary care physicians can use a variety of assessments to help diagnose dementias, she said. These include the Montreal Cognitive Assessment (MoCA), which takes about 10 minutes to administer, or an MRI to determine the level of hippocampal atrophy. Blood tests for p-tau 217 and other plasma tests can stratify risk and guide referrals to a neurologist. Clinicians also should look for reversible causes of memory complaints, she said, such as deficiencies in vitamin B12, folate, or the thyroid hormone.

"There aren't enough behavioral neurologists around to work up every single person who has memory problems," Seshadri said. "We really need to partner on educating and learning from our primary care partners as to what challenges they face, advocating for them to be able to address that, and then sharing what we know, because what we know is an evolving thing."

Other tools primary care clinicians can use in the initial evaluation of dementia include the General Practitioner Assessment of Cognition and the Mini-Cog, as part of annual Medicare wellness visits or in response to patient or caregiver concerns about memory, said Allison Kaplan, MD, a family physician at Desert Grove Family Medical in Gilbert, Arizona, who coauthored a point-of-care guide for the American Academy of Family Physicians. Each of these tests takes just 3-4 minutes to administer.

If a patient has a positive result on the Mini-Cog or similar test, they should return for further dementia evaluation using the MoCA, Mini-Mental State Examination, or Saint Louis University Mental Status examination, she said. Physicians also can order brain imaging and lab work, as Seshadri noted. Dementias often accompany some type of cardiovascular disease, which should be managed, Kaplan said.

Even if a patient or family member doesn't express concern about memory, physicians can look for certain signs during medical visits.

"Patients will keep asking the same question, or you notice they're having difficulty taking care of themselves, especially independent activities of daily living, which could clue you in to a dementia diagnosis," she said.

The sources in this article disclosed no relevant financial relationships.

https://www.medscape.com/viewarticle/cognitive-breakdown-new-memory-condition-primary-care-needs-2024a1000egv

'Feds Accuse Erlanger Health of Paying Docs Outrageous Salaries for Patient Referrals'

 Strapped for cash and searching for new profits, Tennessee-based Erlanger Health System illegally paid excessive salaries to physicians in exchange for patient referrals, the US government alleged in a federal lawsuit.

Erlanger changed its compensation model to entice revenue-generating doctors, paying some two to three times the median salary for their specialty, according to the complaint. 

The physicians in turn referred numerous patients to Erlanger, and the health system submitted claims to Medicare for the referred services in violation of the Stark Law, according to the suit, filed in US District Court for the Western District of North Carolina. 

The government's complaint "serves as a warning" to health care providers who try to boost profits through improper financial arrangements with referring physicians, said Tamala E. Miles, Special Agent in Charge for the US Department of Health and Human Services (HHS) Office of Inspector General (OIG).

In a statement provided to Medscape Medical News, Erlanger denied the allegations and said it would "vigorously" defend the lawsuit. 

"Erlanger paid physicians based on amounts that outside experts advised was fair market value," Erlanger officials said in the statement. "Erlanger did not pay for referrals. A complete picture of the facts will demonstrate that the allegations lack merit and tell a very different story than what the government now claims."

The Erlanger case is a reminder to physicians to consult their own knowledgeable advisors when considering financial arrangements with hospitals, said William Sarraille, JD, adjunct professor for the University of Maryland Francis King Carey School of Law in Baltimore and a regulatory consultant. 

"There is a tendency by physicians when contracting…to rely on [hospitals'] perceived compliance and legal expertise," Sarraille told Medscape Medical News. "This case illustrates the risks in doing so. Sometimes bigger doesn't translate into more sophisticated or more effective from a compliance perspective." 

The Stark Law prohibits hospitals from billing the Centers for Medicare & Medicaid Services (CMS) for services referred by a physician with whom the hospital has an improper financial relationship.

CMS paid Erlanger about $27.8 million for claims stemming from the improper financial arrangements, the government contends. 

"HHS-OIG will continue to investigate such deals to prevent financial arrangements that could compromise impartial medical judgment, increase health care costs, and erode public trust in the health care system," Miles said in a statement. 

Erlanger's financial troubles allegedly started after a previous run-in with the US government over false claims. 

In 2005, Erlanger Health System agreed to pay the government $40 million to resolve allegations that it knowingly submitted false claims to Medicare, according to the government's complaint. At the time, Erlanger entered into a Corporate Integrity Agreement (CIA) with the OIG that required Erlanger to put controls in place to ensure its financial relationships did not violate the Stark Law. 

Erlanger's agreement with OIG ended in 2010. Over the next 3 years, the health system lost nearly $32 million and in fiscal year 2013, had only 65 days of cash on hand, according to the government's lawsuit. 

Beginning in 2013, Erlanger allegedly implemented a strategy to increase profits by employing more physicians, particularly specialists from competing hospitals whose patients would need costly hospital stays, according to the complaint. 

Once hired, Erlanger expected its physicians to treat patients at Erlanger's hospitals and refer them to other providers within the health system, the suit claims. Erlanger also relaxed or eliminated the oversight and controls on physician compensation put in place under the CIA. For example, Erlanger's CEO signed some compensation contracts before its chief compliance officer could review them and no longer allowed the compliance officer to vote on whether to approve compensation arrangements, according to the complaint. 

Erlanger also changed its compensation model to include large salaries for medical director and academic positions and allegedly paid such salaries to physicians without ensuring the required work was performed. As a result, Erlanger physicians with profitable referrals were among the highest paid in the nation for their specialties, the government claims. For example, according to the complaint:

• Erlanger paid an electrophysiologist an annual clinical salary of $816,701, a medical director salary of $101,080, an academic salary of $59,322, and a productivity incentive based on work relative value units (wRVUs). The medical director and academic salaries paid were near the 90th percentile of comparable salaries in the specialty.
• The health system paid a neurosurgeon a base salary of $654,735, a productivity incentive based on wRVUs, and payments for excess call coverage ranging from $400 to $1000 per 24-hour shift. In 2016, the neurosurgeon made $500,000 in excess call payments.
• Erlanger paid a cardiothoracic surgeon a base clinical salary of $1,070,000, a sign-on bonus of $150,000, a retention bonus of $100,000 (payable in the 4th year of the contract), and a program incentive of up to $150,000 per year.

In addition, Erlanger ignored patient safety concerns about some of its high revenue-generating physicians, the government claims. 

For instance, Erlanger received multiple complaints that a cardiothoracic surgeon was misusing an expensive form of life support in which pumps and oxygenators take over heart and lung function. Overuse of the equipment prolonged patients' hospital stays and increased the hospital fees generated by the surgeon, according to the complaint. Staff also raised concerns about the cardiothoracic surgeon's patient outcomes. 

But Erlanger disregarded the concerns and in 2018, increased the cardiothoracic surgeon's retention bonus from $100,000 to $250,000, the suit alleges. A year later, the health system increased his base salary from $1,070,000 to $1,195,000.

Health care compensation and billing consultants alerted Erlanger that it was overpaying salaries and handing out bonuses based on measures that overstated the work physicians were performing, but Erlanger ignored the warnings, according to the complaint. 

Administrators allegedly resisted efforts by the chief compliance officer to hire an outside consultant to review its compensation models. Erlanger fired the compliance officer in 2019. 

The former chief compliance officer and another administrator filed a whistleblower lawsuit against Erlanger in 2021. The two administrators are relators in the government's July 2024 lawsuit. 

The Erlanger case is the latest in a series of recent complaints by the federal government involving financial arrangements between hospitals and physicians.

In December 2023, Indianapolis-based Community Health Network Inc. agreed to pay the government $345 million to resolve claims that it paid physicians above fair market value and awarded bonuses tied to referrals in violation of Stark Law. 

Also in 2023, Saginaw, Michigan-based Covenant HealthCare and two physicians paid the government $69 million to settle allegations that administrators engaged in improper financial arrangements with referring physicians and a physician-owned investment group. In another 2023 case, Massachusetts Eye and Ear in Boston agreed to pay $5.7 million to resolve claims that some of its physician compensation plans violated the Stark Law. 

Before entering into a financial arrangement with a hospital, it's also important to examine what percentile the aggregate compensation would reflect, law professor Sarraille said. The Erlanger case highlights federal officials' suspicion of compensation, in aggregate, that exceeds the 90th percentile and increased attention to compensation that exceeds the 75th percentile, he said. 

To research compensation levels, doctors can review the Medical Group Management Association's annual compensation report or search its compensation data. 

Before signing any contracts, Sarraille suggests physicians also consider whether the hospital shares the same values. Ask physicians at the hospital what they have to say about the hospital's culture, vision, and values. Have physicians left the hospital after their practices were acquired? Consider speaking with them to learn why. 

Keep in mind that a doctor's reputation could be impacted by a compliance complaint, regardless of whether it's directed at the hospital and not the employed physician, Sarraille said. 

"The [Erlanger] complaint focuses on the compensation of specific, named physicians saying they were wildly overcompensated," he said. "The implication is that they sold their referral power in exchange for a pay day. It's a bad look, no matter how the case evolves from here." 

Physicians could also face their own liability risk under the Stark Law and False Claims Act, depending on the circumstances. In the event of related quality-of-care issues, medical liability could come into play, Sarraille noted. In such cases, plaintiffs' attorneys may see an opportunity to boost their claims with allegations that the patient harm was a function of "chasing compensation dollars," Sarraille said. 

"Where that happens, plaintiff lawyers see the potential for crippling punitive damages, which might not be covered by an insurer," he said.

https://www.medscape.com/viewarticle/government-accuses-health-system-paying-docs-outrageous-2024a1000ed1

EU's Breton says Musk must comply with EU law ahead of Trump interview

 EU industry chief Thierry Breton told billionaire Elon Musk in a letter on Monday he must comply with EU law ahead of Musk's interview with U.S. presidential candidate Donald Trump on social media platform X.

The interview, scheduled for 8PM Eastern Time (0000 Tuesday GMT), will also be accessible to users in the EU, Breton wrote, adding: "In this context, I am compelled to remind you of the due diligence obligations set out in the Digital Services Act (DSA)."

"DSA obligations apply without exceptions or discrimination to the moderation of the whole user community and content of X (including yourself as a user with over 190 million followers) which is accessible to EU users and should be fulfilled in line with the risk-based approach of the DSA, which requires greater due diligence in case of a foreseeable increase of the risk profile", Breton wrote in his letter.

The DSA law requires very large platforms to do more to tackle illegal content and risks to public security.

Last month, EU tech regulators ruled that X breached the DSA and that it deceived users through its use of blue checkmarks.

X said it disagreed with the EU's assessment on how it complies with the DSA while owner Musk threatened litigation.

https://uk.news.yahoo.com/eus-breton-says-musk-must-173032435.html

These Six Drivers Are Gone, And That's Why The Global Economy Is Toast

 by Charles Hugh Smith via OfTwoMinds blog,

The global economy is toast. All that's left is the distribution of the burned bits.

The six one-offs that drove growth and pulled the global economy out of bubble-bust recessions for the past 30 years have all reversed or dissipated. Absent these one-off drivers, the global economy is stumbling off the cliff into a deep recession without any replacement drivers. Colloquially speaking, the global economy is toast.

Here are the six one-offs that won't be coming back:

1) China's industrialization.

2) Growth-positive demographics.

3) Low interest rates.

4) Low debt levels.

5) Low inflation.

6) Tech productivity boom.

Cutting to the chase, China bailed the world out of the last three recessions triggered by credit-asset bubbles popping: the Asian Contagion of 1997-98, the dot-com bubble and pop of 2000-02, and the Global Financial Crisis of 2008-09. In each case, China's high growth and massive issuance of stimulus and credit (a.k.a. China's Credit Impulse) acted as catalysts to restart global expansion.

The boost phase of picking low-hanging fruit via rapid industrialization boosting mercantilist exports and building tens of millions of housing units is over. Even in 2000 when I first visited China, there were signs of overproduction / demand saturation: TV production in China in 2000 had overwhelmed global and domestic demand: everyone in China already had a TV, so what to do with the millions of TVs still being churned out?

China's model of economic development that worked so brilliantly in the boost phase, when all the low-hanging fruit could be so easily picked, no longer works at the top of the S-Curve.

Having reached the saturation-decline phase of the S-Curve, these policies have led to an extreme concentration of household wealth in real estate. Those who favored investing in China's stock market have suffered major losses. (see chart below)

This is the problem with overproduction as a model of endless growth: it eventually overwhelms demand and the income needed to pay for it.

Where China's workforce was growing during the boost phase, now the demographic picture has darkened: China's workforce is shrinking, the population of elderly retirees is soaring, and so the cost burdens of supporting a burgeoning cohort of retirees will have to be funded by a shrinking workforce who will have less to spend / invest as a result.

This is a global phenomenon, and there are no quick and easy solutions. Skilled labor will become increasingly scarce and able to demand higher wages regardless of any other factors, and that will be a long-term source of inflation. Governments will have to borrow more--and probably raise taxes as well--to fund soaring pension and healthcare costs for retirees. This will bleed off other social spending and investment.

The era of zero-interest rates and unlimited government borrowing has ended. As Japan has shown, even at ludicrously low rates of 1%, interest payments on skyrocketing government debt eventually consume virtually all tax revenues. Higher rates will accelerate this dynamic, pushing government finances to the wall as interest on sovereign debt crowds out all other spending. As taxes rise, households are left with less disposable income to spend on consumption, leading to stagnation.

At the start of the cycle, global debt levels (government and private-sector) were low. Now they are high. The boost phase of debt expansion and debt-funded spending is over, and we're in the stagnation-decline phase where adding debt generates diminishing returns.

The era of low inflation has also ended for multiple reasons. Exporting nations' wages have risen sharply, pushing their costs higher, and as noted, skilled labor in developed economies can demand higher wages as this labor cannot be automated or offshored. Offshoring is reversing to onshoring, raising production costs and diverting investment from asset bubbles to the real world.

Higher costs of resource extraction, transport and refining will push inflation higher. So will rampant money-printing to "boost consumption."

The tech productivity boom was also a one-off. Economists were puzzled in the early 1990s by the stagnation of productivity despite the tremendous investments made in personal and corporate computers, a boom launched in the mid-1980s with Apple's Macintosh and desktop publishing, and Microsoft's Mac-clone Windows operating system.

By the mid-1990s, productivity was finally rising and the emergence of the Internet as "the vital 4%" triggered the adoption of the 20% which then led to 80% getting online combined with distributed computing to generate a true revolution in sharing, connectivity and economic potential.

The buzz around AI holds that an equivalent boom is now starting that will generate a glorious "Roaring 20s" of trillions booked in new profits and skyrocketing productivity as white-collar work and jobs are automated into oblivion.

There are two problems with this story:

1) The projections are based more on wishful thinking than real-world dynamics.

2) If the projections come true and tens of millions of white-collar jobs disappear forever, there is no replacement sector to employ the tens of millions of unemployed workers.

In the previous cycles of industrialization and post-industrialization, agricultural workers shifted to factory work, and then factory workers shifted to services and office work. There is no equivalent place to shift tens of millions of unemployed office workers, as AI is a dragon that eats its own tail: AI can perform many programming tasks so it won't need millions of human coders.

As for profits, as I explained in There's Just One Problem: AI Isn't Intelligent, and That's a Systemic Risk, everyone will have the same AI tools and so whatever those tools generate will be overproduced and therefore of little value: there is no pricing power when the world is awash in AI-generated content, bots, etc., other than the pricing power offered by monopoly, addiction and fraud--all extreme negatives for humanity and the global economy.

Either way it goes--AI is a money-pit of grandiose expectations that will generate marginal returns, or it wipes out much of the middle class while generating little profit--AI will not be the miraculous source of millions of new high-paying jobs and astounding profits.

What we now have is a hyper-centralized, hyper-connected (i.e. tightly bound), hyper-globalized and hyper-financialized global economy of extreme fragility, over-indebted and hollowed out by speculation, fraud, corruption, leverage, sclerosis and by an unbreakable addiction to doing more of what's failed spectacularly.

The downside slide into recession and polycrisis-collapse is not as fun as the boost phase.

Concentrating assets, capital, control, debt and leverage also concentrates risk, which eventually leaks through the illusion of resilience and melts down the entire economy:

In a word, the global economy is toast. All that's left is the distribution of the burned bits. Those who end up with collapsing currencies experience hyper-inflation, and those who manage to wallow in deflation experience stagnation as the best-case scenario. In all cases, the pool of creaky policies from the 1930s that will actually work has dried up: all the "fixes" that were solutions in the past are now accelerating the slide into a post-bubble recession with no visible exit.

*  *  *

https://www.zerohedge.com/economics/these-six-drivers-are-gone-and-thats-why-global-economy-toast