Speech analysis tech for ALS gets FDA breakthrough tag

 Software that can be used to monitor patients with neurodegenerative disorder amyotrophic lateral sclerosis (ALS) using their voice patterns has been granted breakthrough status by the FDA, which could speed up its journey to approval.

Aural Analytics’ Speech Vitals-ALS app is used to collect and analyse speech recordings in ALS patients – either in clinics or their own homes – to help neurologists track how quickly their disease is progressing.

It is also being used to gauge whether drug treatments are having an impact on ALS in clinical trials, and in time Aural Analytics is hoping it could be used to diagnose patients with the disease.

One of the hallmarks of ALS is damage to motor neurons in the bulbar region of the brain, which can have a devastating impact on patients’ ability to communicate, but it is hard to pick up in the early stages using conventional ALS rating scales.

Speech Vitals-ALS has been developed to pick up early deterioration in speech patterns, such as articulatory precision (AP) and speaking rate (SR) that could serve as ‘vocal biomarkers’, providing early detection and tracking of ALS symptoms from just a few minutes of speech samples taken from patients using app-based tasks.

The vocal biomarkers could also be used to predict declines in other bodily functions affected by ALS, like swallowing and breathing.

“Achieving breakthrough designation for Speech Vitals-ALS is explicit validation that the FDA sees the potential in the […] platform to provide for more effective management of this devastating disease,” said Jeremy Moore, Aural Analytics’ director of quality assurance and regulatory affairs.

The company is currently trying to secure regulatory approval of the software under the de novo clearance pathway for medical devices – used for products which have no similar devices on the market with which the company can claim substantial equivalence.

Speech Vitals-ALS was recently used in a placebo-controlled clinical trial evaluating Prilenia Therapeutics’ sigma-1 receptor antagonist pridopidine in patients with ALS.

While the study wasn’t able to show a statistically significant impact on ALS progression, the speech analytics software did suggest that prilopidine was slowing the decline in several markers related to speech and bulbar function, including AP, SR, sustained phonation, and articulation rate.

The pridopidine study was being conducted as part of the HEALEY ALS Platform trial, which has been designed to accelerate the development of treatments by testing multiple drugs for individuals with ALS.

Aural Analytics also intends to develop its Speech Vitals software for other neurodegenerative disorders, including Parkinson’s disease.

https://pharmaphorum.com/news/speech-analysis-tech-als-gets-fda-breakthrough-tag

CDC teams studying East Palestine health risks got sick during investigation

 Members of the Centers for Disease Control and Prevention’s (CDC) team studying the effects of the train derailment in East Palestine, Ohio, became briefly ill earlier this month, the agency told The Hill on Friday.

A CDC spokesperson said seven of the 15 investigators experienced symptoms including sore throat, headache, coughing and nausea, which are similar to those that residents of the area reported following the train crash in early February, which allowed hazardous materials to escape into the air, water and soil of the area. 

CNN reported that whether exposure to the chemicals or fatigue caused the symptoms is unclear, but an official familiar with the cases told the outlet that the workers were suspicious that they became ill at the same time and had the same symptoms. 

The investigators were taking a house-to-house survey of residents living near the area of the derailment. 

The agency spokesperson said that the symptoms resolved for most team members later in the afternoon and all workers were able to continue their work within 24 hours. They said the affected members have not reported any lingering health issues. 

The spokesperson said the survey collection process will conclude Friday, and staff will then analyze the data and provide it to Ohio and Pennsylvania state health officials.

The derailment to the Norfolk Southern train allowed toxic chemicals such as vinyl chloride, an explosive cancer-causing substance used in certain materials like plastic, to leak out. Officials intentionally burned the substance as part of a controlled release to avoid a potential explosion that would have been more damaging to the region. 

The derailment forced thousands of residents to evacuate their homes for a few days. Officials said they did not detect any chemicals in the water or air that would pose a threat to people’s health, but residents reported experiencing symptoms such as difficulty breathing and rashes when they returned. 

Norfolk Southern is facing multiple lawsuits, including a class-action case from East Palestine residents and complaints from the state of Ohio and the Justice Department. 

The affected investigators were a part of the CDC’s Agency for Toxic Substances and Disease Registry, which probes the effects of chemical releases on people’s health. They ask those they survey about where they have spent time and any symptoms they or their pets have had.

https://thehill.com/policy/healthcare/3927743-cdc-teams-studying-east-palestine-health-risks-got-sick-during-investigation-cnn/

GAO 'praises FDA for diverting restaurant food to grocery stores'

 A report released this week by the government’s internal watchdog praised the Food and Drug Administration (FDA) for allowing food that was meant for restaurants to be stacked instead on grocery store shelves as inflation following the pandemic hit 40-year highs.

Inflation has been coming down throughout the economy, as Friday’s personal consumption expenditures (PCE) price index dropped to 5 percent annually in February from 5.4 percent in January.

But food prices are bucking this trend and remaining excessively high.

The latest consumer price index (CPI) put groceries at 10.2 percent more expensive than they were last year. That’s compared to 6 percent annual inflation across the economy as a whole.

The new report from the Government Accountability Office (GAO) said that the FDA helped to alleviate some of these soaring prices by making changes to their regulations.

“By relaxing regulations to let food made for restaurants be diverted to grocery stores, the FDA helped to avert food shortages that could’ve further increased prices during the COVID-19 pandemic,” the report found.

“From 2021-22, U.S. retail food prices rose by 11 percent — the largest annual increase in over 40 years. Rising food prices particularly impact low-income consumers, who spend about 30 percent of their income on food. Many factors influencing the food supply chain can affect retail food prices, such as global trade issues, pandemics, animal and plant disease outbreaks, and war,” the report said.

The report also noted the spike in food prices that followed the outbreak of war between Russia and Ukraine.

The component costs that go into determining the prices of goods and services fall into the three main categories of input costs, labor costs and profits.

While the labor share of pricing has fallen over course of the pandemic, the profit share of pricing has risen, Commerce Department data shows. 

Unit labor costs have fallen from about 60 percent to 58 of prices since the beginning of 2020, while profit margins have increased from around 12 percent to 15 percent, according to calculations by The Hill.

This has led some economists to term the current inflation a “sellers inflation,” meaning that it originates with profit margins as opposed to labor costs. That’s different from the high inflation that hit the economy in the 1970s, which is widely agreed to have been related to a wage-price spiral.

There are long-term tailwinds to this trend, which show that markups and profits have been rising for decades.

“In 1980, aggregate markups start to rise from 21 percent above marginal cost to 61 percent now,” economist Jan De Loecker and others wrote in an influential 2020 study for the Quarterly Journal of Economics. “We also find an increase in the average profit rate from 1 percent to 8 percent.”

A 2020 paper by Simcha Barkai of the London Business School produced a similar long-term result. 

“A large increase in the share of pure profits offsets declines in the shares of both labor and capital Industry data show that increases in concentration are associated with declines in the labor share,” Barkai wrote in his paper.

Some food producers have recently been accused of price gouging. Mississippi-based egg producer Cal-Maine recently saw its profits leap by more than 700 percent, as egg prices have soared to record levels

Many commentators have noted that supply chain disruptions during the pandemic have given cover to private firms that are incentivized by the market to raise their prices as much as they can.

Almost all government agencies adjusted their regulatory practices in response to the coronavirus pandemic, and these changes are being assessed at various levels of government.

https://thehill.com/business/3928666-watchdog-report-praises-fda-for-diverting-restaurant-food-to-grocery-stores/

Real Income Was Negative in 2022 Q4, Big Negative Revisions to GDP

 Don't discount the possibility that a recession started in 2022 Q4. That's the message from the BEA's revised GDP numbers.

• 
  

Chart Notes

• Real final sales are the true bottom line estimate of GDP. The rest is inventory adjustment that nets to zero over time.
• Real Final Private Domestic ignores government spending and exports. 

Real Final Private Domestic Sales was a big zero.

Significant Negative GDP Revisions Are Consistent With Recession

On January 26, I commented 4th Quarter 2022 GDP Is Much Weaker Than Headline Numbers

On February 24, 2023, I commented Significant Negative GDP Revisions for 2022 Q4 Are Consistent With Recession

Well, guess what. The BEA revised GDP lower again.

As I have commented many times, heading into recessions the revisions will tend to be heavily negative. Coming out of recessions, revisions tend to be positive.

Real GDI is Negative 1.1 PercentReal Gross Domestic Product (GDP) and Real Gross Domestic Income (GDI) 2022 Q4

Please consider the Gross Domestic Product (Third Estimate) for 2022 Q4.

Real GDP and real GDI are two measures of the same thing. 

The discrepancy is massive. Expect the discrepancy to resolve in the future towards lower GDP. 

Money Supply Is Headed for 6th Month of Contraction

https://mishtalk.com/economics/real-income-was-negative-in-2022-q4-big-negative-revisions-to-gdp

• Real gross domestic product (GDP) increased at an annual rate of 2.6 percent in the fourth quarter of 2022.
• In the third quarter, real GDP increased 3.2 percent. 
• In the second estimate, the increase in real GDP was 2.7 percent. 
• The revision primarily reflected downward revisions to exports and consumer spending. Imports, which are a subtraction in the calculation of GDP, were revised down. 

Real GDP, Real Final Sales, Real GDI 

Real GDP, Real Final Sales, Real GDI 2022 Q4

Real GDP, Real Final Sales 

Brin, Pritzker, Zuckerman And Ovitz Issued Subpoenas In Epstein Lawsuit

 Billionaires Sergey Brin, Thomas Pritzker, Mortimer Zuckerman and Michael Ovitz were issued subpoenas this week by the US Virgin Islands as part of its lawsuit against JPMorgan over the bank's relationship with now-deceased pedophile Jeffrey Epstein, according to the Wall Street Journal, citing people familiar with the matter.

The four men are some of the wealthiest people in the U.S., and it couldn’t be determined why they were being asked for the communications and documents. In civil cases, lawyers can use subpoenas during the discovery process to get information from people who aren’t a party to a lawsuit but could provide evidence related to the case. -WSJ

JPMorgan is being sued by the US Virgin Islands along with several Epstein accusers in a combined case over Epstein's sex trafficking operation. The plaintiffs claim that the bank facilitated abuse by allowing Epstein to remain a client while helping send money to his victims. The lawsuit also alleges that JPMorgan turned a blind eye to Epstein's activities after receiving referrals for high-value business opportunities.

Hyatt Hotels Corp.’s Executive Chairman Thomas Pritzker and Google co-founder Sergey Brin.Photo: Franck Robichon/European Pressphoto Agency, Fabrice Coffrini/AFP/Getty Images

Brin is a co-founder of Google and sits on the board of parent company Alphabet. Pritzker is executive chairman of Hyatt Hotels. Ovitz is a venture capitalist and co-founder of the Creative Artists Agency (CAA), and Zuckerman is a real-estate billionaire and owns US News & World Report.

Michael Ovitz, venture capitalist and former Hollywood agent, and Mort Zuckerman, real-estate investor. Photo: Brendan McDermid/Reuters, Victor J. Blue/Bloomberg News

As we noted on Tuesday, JPMorgan CEO Jamie Dimon is expected to be deposed under oath regarding the bank's relationship with Epstein - who banked with JPMorgan for 15 years until it eventually cut ties with the convicted sex offender in 2013.

"Jamie Dimon knew in 2008 that his billionaire client was a sex trafficker," argued US Virgin Islands attorney Mimi Liu during a March hearing in front of Manhattan US District Judge Jed Rakoff, referring to the year Epstein was first criminally charged with sex crimes, CNBC reported earlier this month.

Lawyers have questioned several JPMorgan employees so far in this case and another filed by an unnamed woman who accused Epstein of sexual abuse. The cases are running together in Manhattan federal court.

JPMorgan has sought to have the lawsuits dismissed. The bank has denied that it aided Epstein and has sought to blame any relationship on former executive Jes Staley, whom the bank has sued. Mr. Staley has maintained he was friendly with Epstein but never knew about his alleged crimes. -WSJ

"If Staley is a rogue employee, why isn’t Jamie Dimon?" Liu said during the hearing to discuss the bank's efforts to have the USVI lawsuit against the bank dismissed, referring to former JPMorgan executive Jes Staley, who is not named in the current litigation.

"Staley knew, Dimon knew, JPMorgan Chase knew," Liu continued, noting that there were several cash transfers and wire transfers made by the prolific pedophile (Epstein), including several hundreds of thousands of dollars paid to several women which should have been flagged as suspicious.

https://www.zerohedge.com/political/google-co-founder-sergey-brin-other-billionaires-slapped-subpoenas-epstein-lawsuit

China Outpacing US Military At 'Disturbing' Rate: Gen. Milley

 by Samantha Flom via The Epoch Times (emphasis ours),

China is on a trajectory to achieve military superiority over the United States by midcentury, Joint Chiefs of Staff Chairman Gen. Mark Milley warned members of Congress on March 29.

Testifying at a House Armed Services Committee hearing on the Department of Defense’s 2024 budget requests, Milley noted that China has a national goal to be a “global coequal” with the United States and “militarily superior” by 2049.

“They’re on that path to do that, and that’s really disturbing,” he said. “That’s really bothersome. And we’re going to have to not only keep pace, but we have to outpace that, and that will assure the peace.”

Of particular concern is China’s nuclear development program, Milley said, holding that there is little the United States could do to “stop, slow down, disrupt, interdict, or destroy” it.

Milley’s unease echoed that of U.S. Air Force Secretary Frank Kendall, who told Congress on Tuesday that China’s expansion of its nuclear force was the most “disturbing” military threat he’d seen in his half-century career.

For months, the Pentagon has been sounding the alarm over China’s nuclear moves, warning in December that the country was on pace to quadruple its number of nuclear warheads to 1,500 by 2035.

Currently, the Defense Department estimates China’s nuclear warhead count to be more than 400. And while that number may seem small compared with the United States’ stockpile of around 3,750, Milley stressed on Wednesday that the communist country’s capabilities should not be underestimated.

“They have a significant nuclear capability today and they have intercontinental ballistic missiles that can range the United States,” he said. “That is obviously bothersome.”

The general also noted that the situation is further complicated by the strengthening relationship between China and Russia, which he described as “troublesome.”

“We are facing two nuclear-armed great powers,” he emphasized. “So, the principles of the Cold War of deterrence still obtain, but now it’s more complicated because it’s two versus one.”

And with the added threat of Iran joining the mix, Milley predicted, “Those three countries together are going to be problematic for many years to come.”

A New Cold War?

Milley’s remarks came on the heels of the release of a new Heritage Foundation report (pdf), which holds that the United States has entered into a new Cold War with China and outlines a defensive plan to counter the threat.

https://www.zerohedge.com/geopolitical/china-outpacing-us-military-disturbing-rate-gen-milley

CDC made dozens of basic data errors on COVID, epidemiologists find

 The CDC found itself hoist with its own petard by making 25 basic statistical and numerical errors related to COVID-19, particularly with regard to children, while purporting to expose COVID vaccine misinformation, according to an analysis led by University of California San Francisco epidemiologists.

The preprint, which has not yet been peer-reviewed, documented 20 errors that "exaggerated the severity of the COVID-19 situation" and three that "simultaneously exaggerated and downplayed" severity, while one each was neutral or exaggerated vaccine risks. 

More than half were from 2022, but nearly as many were made in the first two months of 2023 as in all of 2021, they found. Several errors were related to the agency's COVID data tracker, which failed to align with its National Center for Health Statistics (NCHS), and the CDC corrected at least in part 13 of the 16 errors brought to its attention.

The paper emphasizes how widely CDC errors can spread even if they are later corrected, with YouTube and Spotify linking its website on videos and podcasts that discuss COVID and the wide deference to CDC guidance in schools, businesses and healthcare facilities.

"The errors are damning," coauthor Vinay Prasad, a former National Institutes of Health fellow, said on Twitter. "Basic counts of dead kids, causes of childhood death. Unacceptable incompetence."

UCSF's Alyson Haslam, a former CDC fellow who works in Prasad's lab, made the final call on CDC errors that Prasad, Tracy Beth Hoeg and independent Georgia COVID analyst Kelley Krohnert collectively agreed "were indisputable and incorrect, as a matter of fact, and not preference or opinion."

The trio conducted "real time" review of news sources, Advisory Committee on Immunization Practices (ACIP) meetings and materials, the agency's Morbidity and Mortality Weekly Report and the Twitter accounts of the CDC and its director, as well as reports sent to them by others, going back to 2021.

The errors were heavily weighted toward exaggerating COVID's risk to children. Fifteen of the 16 pertaining to children's data "enhanced the perceived risk" of the virus and more than half the total errors involved mortality statistics, with the CDC data tracker "consistently" reporting higher deaths for children and adolescents than did NCHS.

Perhaps the most consequential error was the CDC's repeated promotion of a preprint that deemed COVID a "top 5" cause of death in children, which the agency only corrected in one place months later.

That paper compared 26 months of COVID deaths, where the virus was "one of several contributing causes to deaths," to 12 months of deaths from other causes that were "identified as the single underlying cause of death ... which by design exaggerates" the COVID risk to kids, the paper says.

Not only was the claim made in ACIP and FDA Vaccines and Related Biological Products Advisory Committee meetings, but also at a White House briefing by CDC Director Rochelle Walensky and by ACIP's chair in a subsequent meeting "after the errors were identified." Only ACIP's page on "vaccination evidence for young children" includes the correction.

The agency was plain sloppy in other errors, the authors allege. It listed pediatric deaths as 4% of COVID deaths when it meant to write 0.04% and gave a lower estimated rate of pediatric infections than symptomatic illness, with some errors remaining live for seven months.

"These errors have been made repeatedly and were likely to have affected discussion of pandemic policies," particularly the CDC's guidance calling for "school closures, mask mandates, and strong recommendations for vaccinations and multiple boosters even among children who have recovered from the virus," the authors conclude.

The CDC did not respond to queries for its response to the paper.

The FDA's evidence for full approval of Pfizer's COVID antiviral Paxlovid, shared with its advisory committee on antimicrobial drugs, also came under scrutiny.

The advisers voted in mid-March to approve the two-drug treatment for high-risk adults while warning that many patients could have harmful drug interactions, CNBC reported. The agency will make the final decision in May. (Pfizer long ago acknowledged Paxlovid is not useful against household transmission.)

While the FDA's briefing packet emphasized the infrequency of Paxlovid "rebound" infections — which hit the president, his COVID adviser, first lady and both FDA and CDC commissioners, all up to date on COVID jabs — its cited evidence only applies to a sliver of potential Paxlovid patients.

The Pfizer studies gave five-day treatments to unvaccinated high-risk patients (EPIC-HR) and vaccinated high-risk or unvaccinated low-risk patients before and after the Omicron variant wave (EPIC-SR). Only EPIC-HR found "any meaningful difference" compared to a placebo, a 5.6% absolute reduction and 86% relative reduction.

The FDA emphasized the "symptom rebound" rates were similar between Paxlovid and placebo arms across both studies, around 10-16%. This shows that for a "subset" of infections, regardless of Paxlovid, "virologic and/or symptomatic rebound may occur as part of the natural progression and resolution of COVID-19 disease." 

A different graph on "viral RNA rebound," however, found notably higher rates in the Paxlovid arm in EPIC-HR and EPIC-SR's Omicron period. 

In a lengthy review of the FDA evidence, University of Minnesota infectious disease researcher David Boulware said it actually shows Paxlovid is "likely near zero benefit" for under-60s with a "normal immune system" and vaccine- or infection-induced immunity.

Before the Paxlovid vote, National Institutes of Allergy and Infectious Diseases scientist Margery Smelkinson questioned its emergency use authorization starting at age 12 in spite of dramatically different COVID risk by age. She noted Pfizer ended EPIC-SR early after finding no "statistically significant evidence of benefit." 

A member of the Norfolk Group of scientists, physicians and policy experts that recently published a "blueprint" for a potential COVID truth commission, Smelkinson pointed to the Paxlovid section of their report, which emphasizes the lack of rigorous data on who actually benefits from the treatment.

Prasad also questioned the quality of evidence for Paxlovid, including a Lancet Infectious Diseases observational study that found "the curves already split" between treatment and placebo groups at "Day 0," which he said indicates immortal time bias.

"Non randomized evidence will forever be plagued by differences in people who get pax and those who do not (likely being rich, health literate and well connected gets you more pax!)," he wrote in his newsletter in February.

The FDA declined to comment on the criticism of its proffered evidence. "We can’t comment on pending applications," press officer Chanapa Tantibanchachai wrote in an email.

https://justthenews.com/government/federal-agencies/unacceptable-incompetence-cdc-made-dozens-basic-data-errors-covid