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Thursday, April 6, 2023

Former Biden Aide Testimony 'Undermines' White House Narrative On Classified Docs: Comer

 by Frank Fang via The Epoch Times (emphasis ours),

The White House’s narrative on President Joe Biden’s handling of classified documents is being undermined by the congressional testimony of Biden’s former executive assistant, Kathy Chung, according to House Oversight Committee Chairman, James Comer (R-Ky.)

Comer released a statement on April 4, saying that Chung provided “startling information that undermines the Biden White House’s narrative on the matter” when she appeared before the panel for a transcribed interview.

“Today we learned that when Joe Biden left the vice presidency, boxes containing classified documents, vice presidential records, and other items were stored in three different locations around the Washington, D.C. area, including an office near the White House, an office in Chinatown, and eventually the Penn Biden Center,” Comer said.

Chung, who is now the Pentagon’s Deputy Director of Protocol, was one of the staffers who helped pack Biden’s materials at the end of his vice presidency, according to media reports. The materials Chung assisted in packing eventually ended up at the Penn Biden Center for Diplomacy and Global Engagement at the University of Pennsylvania.

Biden’s lawyers found a “small number” of records with classified markings in what was described as “a locked closet” at the Penn Biden Center on Nov. 2, 2022, according to Richard Sauber, special counsel to the president. The records were turned over to the National Archives and Records Administration (NARA) the next day.

On Jan. 10, one day after Sauber’s disclosure, Biden confirmed that documents were founded in the closet and added that he was “surprised to learn” that classified documents were found in his former private office.

However, Comer said Chung’s testimony disputed the locked-closet claim.

“At some point, the boxes containing classified materials were transported by personal vehicles to an office location,” Comer said. “The boxes were not in a ‘locked closet’ at the Penn Biden Center and remained accessible to Penn Biden employees as well as potentially others with access to the office space.”

Biden’s term as vice president ended in January 2017. A month later, he became an honorary professor at the University of Pennsylvania and was given the role of leading the school’s Penn Biden Center, which officially opened in February 2018. According to the university’s website, Biden also had an office on the school’s campus in Philadelphia.

Biden was placed on unpaid leave in April 2019, when he announced he was running for president.

There have been concerns about possible links between the center and the Chinese Communist Party (CCP), but a university spokesperson has denied that any Chinese money was funneled to the center.

https://www.zerohedge.com/political/former-biden-aides-testimony-undermines-white-house-narrative-classified-docs-comer

FDA's Peter Marks lays out plan to boost gene therapy approvals

 The FDA has approved 12 gene therapies so far, and the agency's top drug regulator wants to see the road ahead illuminated with green lights.

If the FDA only approves two or three per year over the next few years, Peter Marks, M.D., head of the FDA’s Center for Biologics Evaluations and Research (CBER), says "that’s a failure.” His comments came at a webinar Tuesday hosted by the Alliance for a Stronger FDA, a lobbying group for the agency. 

“Success would be … if not exponential, at least some logarithmic progression towards more and more gene therapies being approved,” he said. The agency has approved 12 gene therapies to date, according to Marks, five of which came in 2022. 

To get there, Marks and CBER have a four-poin plant: improve manufacturing through new research, clarify the use of the accelerated approval pathway for gene therapies, coordinate regulatory decisions with other regulators and launch an Operation Warp Speed for rare diseases. Easy, right? 

Here’s the hitch: Executing these goals requires adequate staffing, a perennial issue for the agency that’s long struggled with one of the widest revolving doors in government. Marks said that while the latest user fees reauthorization expanded head count, talent is constantly being poached. 

“[W]e still also have to deal with the challenges of a staff that is in high demand in private industry, particularly in the areas that we most want to retain,” he said, highlighting gene therapy and chemistry, manufacturing and controls as areas of focus. 

But fending off enticing job offers is a given. Allowing innovation in the drug industry to lap regulators’ efforts is not. Marks underscored that making the manufacturing process for gene therapies more efficient is a critical next step, saying that the agency is working on funding grants that could go toward automating the process. One proposal by Marks is to streamline the regulatory review of the viral vectors used to deliver gene therapies, including toxicology and manufacturing information. 

His words and proposals come as exorbitant development costs and small commercial markets have thwarted past efforts by companies and foundations to make lifesaving treatments available even when the science is compelling. Marks commended these efforts and says the agency must support them.

"I am incredibly grateful for the foundations that are trying to work on gene therapy now, but they're struggling like salmon swimming upstream,” he said. 

The reality, however, is that Marks’ gene therapy reforms are but one ball among many that the center is juggling. Namely, CBER continues to manage an onslaught of COVID-related work. Marks said the U.S. will be “laughingstocks” if it does not build and maintain a national surveillance system for infectious diseases and that there are currently significant data gaps as a result of heavy reliance on state-by-state reporting. 

“I'm sorry, but the nightmare is not over,” he said. “Just because you had a nightmare last night doesn't mean that you can't have one tomorrow night.

He said the amount of work left to the agency remains significant, as emergency use authorization applications morph into full approval applications, requiring more detailed regulatory analysis. The agency also has to stay on top of the latest circulating virus variants—a nod to Marks' surveillance qualms—so that manufacturers can update vaccine formulas to the most prevalent strains. Marks says on top of all of this, CBER and the FDA need to keep their eyes on other viruses of concern to prevent being caught flatfooted in the event that a new disease spreads quickly.

“The way we were able to actuate Operation Warp Speed was by, essentially, pulling people from other projects, and we’ll need in the future to think about ways to avoid having to do that,” he said. 

https://www.fiercebiotech.com/biotech/thats-failure-fdas-marks-says-gene-therapy-approvals-must-rapidly-increase

Takeda trims early-stage efforts in AAV gene therapy

 Takeda is moving away from early-stage R&D work in adeno-associated virus-based gene therapies and the rare hematology spaces, with an unknown number of employees set to “transition out” of the pharma.

The company has informed its team that discovery and preclinical efforts in AAV gene therapy will be discontinued, alongside research and preclinical work in rare hematology, a spokesperson confirmed with Fierce Biotech via email.

The move is supposed to help focus resources on core therapeutic areas and the company's late-stage clinical programs such as oral TYK2 inhibitor TAK-279, according to the spokesperson. That asset is under development for several autoimmune diseases and is currently being assessed in a phase 2b trial for plaque psoriasis as well as a phase 2b study for patients with active psoriatic arthritis.

“We are focused on retaining and providing meaningful work for those whose roles are impacted and where possible, we will reassign individuals to similar roles,” the spokesperson said.

Takeda is also working to support the team involved in AAV gene therapy activities as it “explores externalization strategies."

"We are engaging with our AAV partners to discuss next steps for those programs," the Takeda spokesperson said, though they did not specify further. "Also, we will maintain some strategic investments in non-viral gene therapy—including some partnerships having potential applications to programs across our core therapeutic areas of gastrointestinal and inflammation, neuroscience and oncology plus cell therapies."

While the pharma has invested heavily in gene therapy in the last few years—striking up 10 gene therapy deals from March 2020 to May 2022, with an estimated $9 billion biobucks on the table—most investments aren't in AAV-based gene therapies. Some companies that may be impacted include Codexis, which Takeda has partnered with on preclinical work assessing the biotech's recombinant AAV-based gene therapy for the potential treatment of Fabry disease.  

Takeda also signed a $1.12 billion biobucks deal with Selecta Biosciences, a biotech that touts its platform's potential to induce AAV vector-specific immune tolerance. Another partnership at risk is a $3.6 billion pact with Poseida, which takes aim at developing nonviral in vivo gene therapy programs for the hereditary bleeding disorder hemophilia A.

The new changes won’t affect Takeda’s clinical development pipeline or its commercial products, such as the approved antiviral Livtencity for post-transplant patients that have developed a cytomegalovirus infection or the midstage kidney disease antibody treatment mezagitamab.

“Takeda remains firmly committed to patients with rare diseases and we will maintain our rare disease unit, which will focus on late-stage development programs moving forward,” the spokesperson said.

The Japanese pharma isn't the only large company taking a hard look at the pipeline lately. Pfizer announced a strategy shift earlier this year that includes cutting eight rare disease assets. The Big Pharma is rethinking its approach to rare diseases and exploring “externalization opportunities for a number of highly innovative, niche programs.”

https://www.fiercebiotech.com/biotech/layoffs-loom-takeda-trims-early-stage-efforts-aav-gene-therapy-rare-hematology

Pepsi using AI to track consumer demand, speed up product development

 Food and beverage giant PepsiCo is incorporating artificial intelligence (AI) into its processes for tracking consumer demand and new product development, helping the company boost its sales and bring new products to consumers faster.

PepsiCo Chief Strategy and Transformation Officer Athina Kanioura joined the company in 2020 and began integrating AI into the company’s various processes for sales, research and product development. Kanioura told Axios the company has spent "hundreds of millions" in recent years to do so.

"PepsiCo has always been using technology to engage with our consumers," Kanioura said in a corporate fact sheet on the company’s AI initiatives in 2021. "Now, because of AI we can understand what consumers want and how they want to be engaged. We have millions of data sets to tailor our products and create experiences that are highly customized."

PepsiCo

PepsiCo has spent the last few years integrating AI processes into its sales and product development systems. (Mario Tama/Getty Images / Getty Images)

"The cycles of development have been reduced from years to months," Kanioura added.

For instance, PepsiCo said it used an AI tool to analyze millions of posts on social media, in addition to recipes and menus on the internet. The results of that analysis prompted the company to develop Off The Eaten Path seaweed snacks, a process that took less than a year.

Another example of AI-generated insights informing PepsiCo’s product development came when research found consumers were interested in immunity, which led it to start producing Propel Water with immunity-boosting ingredients, and the new product made it to store shelves six months later.

Naked Juice PepsiCo

Naked juice bottles on a store shelf. An example of PepsiCo’s line of healthy products. (PepsiCo)

Frito-Lay, which is a subsidiary of PepsiCo that features Cheetos as part of its portfolio, has used AI to help ensure the product’s quality in taste and texture remains consistent. 

"We’ve trained a machine ‘brain’ to measure the Cheetos, look at them and detect when adjustments are needed," PepsiCo SVP Foods R&D Denise Lefebvre said in the fact sheet. "This is the ideal application for AI because we know really well what consumers love and value about Cheetos, and we can train a system to understand that."

Another use PepsiCo has considered for AI is helping it determine how to best utilize store shelves and space available for its merchandise at a given grocery or corner store.

TickerSecurityLastChangeChange %
PEPPEPSICO INC.184.36+0.72+0.39%

Magesh Bagavathi, PepsiCo SVP and chief technology officer, said in the fact sheet that a sales rep can take a video of a store’s shelves to create a map of what products need to be stocked.

"You can immediately start tailoring products based on what sells in that region, based on events in that region," Bagavathi said. "There are in-depth insights on seasonality and promotions. It’s highly customized and changes the way we plan."

https://www.foxbusiness.com/markets/pepsi-using-ai-track-consumer-demand-speed-up-product-development

Obesity turning arthritic joint cells into pro-inflammation 'bad apples'

 Being overweight may be physically changing the environment within people's joints, as new research suggests that obesity is promoting pro-inflammatory conditions which worsen arthritis.

In a new study published in Clinical and Translational Medicine today, researchers from the University of Birmingham have found that specific cells in the joint lining tissue (synovium) of patients with osteoarthritis are being changed due to factors associated with obesity.

Previous research has shown that fat tissue that has been metabolically altered by obesity releases proteins called cytokines and adipokines, which are known to promote inflammation around the body. The newly published study funded by Versus Arthritis observed that in cells taken from biopsies of arthritic joints, obesity also changes the environment within the joint itself, leaving cells in the joint vulnerable to being 'turned' into those that promote inflammation.

Dr Susanne Wijesinghe from the Institute of Inflammation and Ageing at the University of Birmingham said: "We have seen that obesity can promote the kind of destructive inflammation in joints that goes far beyond what we might expect to see from wear and tear alone, even in non weight-bearing joints such as the hands.

"Obesity is creating an environment in the body, which is negatively affecting cells called synovial fibroblasts, which are stem cells involved in regulating the lubricating fluid of the joints. The effect is that these cells get recoded into those that promote inflammation within the fluid around the joints. Then, like bad apples in a barrel, they begin to affect the whole joint, increasing secretion of chemicals such as CHI3L1 which degrade the joint and increase the progression of osteoarthritis."

Hips don't lie -- weight isn't driving factor in load-bearing joints

Weight wasn't determined to be the driving factor for impacting the joint cells leading to greater inflammation, the research found.

The team of researchers used biopsy information from a range of joints including both weight-bearing joints such as hips and knees as well as the hands to determine whether the additional physical strain on joints associated with obesity was driving pro-inflammatory cytokines. The results found that there were independent impacts of obesity on load bearing and non-load bearing joints, and that among the 16 patients with BMI of over 30, weight alone didn't account for the molecular changes in those joints.

Simon Jones, Professor in Musculoskeletal Ageing in the Institute of Inflammation and Ageing at the University of Birmingham said: "This research helps us to both design better studies that more accurately understand the different conditions that affect patients with osteoarthritis, and it also better guides the way we develop drugs for the condition in the future.

"Potential targets and ways of delivering drugs can now be specifically considered for patients who do and don't have metabolic changes driven by obesity. In addition, if we treat osteoarthritis patients with obesity as a clinical sub-group we can also see whether specific therapies that address the metabolic element driving the disease can halt that underlying risk."

Zoe Chivers, Director of Services and Influencing at the charity Versus Arthritis said: "This study provides further evidence that osteoarthritis (OA) is not just inevitable 'wear and tear,' but the result of complex and diverse biochemical changes in the joint.

"The research reveals that obesity can lead to a change in the cells in the joint lining to make them more inflammatory, and that these changes occur not only in load bearing joints such as the knee and hips, but also in non-load bearing joints such as the hand.

"These findings greatly enhance our understanding of what can cause osteoarthritis, bringing us closer to discovering more effective treatments in the future."

Journal Reference:

  1. Susanne N. Wijesinghe, Amel Badoume, Dominika E. Nanus, Archana Sharma‐Oates, Hussein Farah, Michelangelo Certo, Fawzeyah Alnajjar, Edward T. Davis, Claudio Mauro, Mark A. Lindsay, Simon W. Jones. Obesity defined molecular endotypes in the synovium of patients with osteoarthritis provides a rationale for therapeutic targeting of fibroblast subsetsClinical and Translational Medicine, 2023; 13 (4) DOI: 10.1002/ctm2.1232

Manganese in California's Central Valley water threatens fetuses and children

 Water in California's Central Valley contains enough manganese to cause cognitive disabilities and motor control issues in children, and Parkinson's-like symptoms in adults.

A naturally occurring metal, manganese is found in water supplies throughout the world. It is regulated as a primary contaminant in many Southeast Asian countries where the climate causes it to leach into groundwater. However, in the U.S. it is regulated only as a secondary contaminant, meaning no maximum level is enforced.

A new UC Riverside-led study shows that, among Central Valley communities, the highest concentrations of manganese are in private, untreated well water systems. However, the researchers also found it in public water systems at higher concentrations than what studies have shown can have adverse health effects.

The study, published in the journal Environmental Science & Technology, not only measured levels of manganese in Central Valley water supplies, but also mapped the highest concentration areas according to annual income levels.

Overall, the research team estimates nearly half of all domestic well water users in the Central Valley live in disadvantaged communities, as defined by annual income. Within this population, nearly 89% have a high likelihood of accessing water that is highly contaminated with manganese.

"It is a relatively small number of people, compared to the total population of the state, who are getting the tainted water. But for them, the health risks are high," said Samantha Ying, UCR soil scientist and principal study investigator. "These people are particularly concentrated in disadvantaged communities, so if they wanted to monitor and treat the water, they would have a hard time doing so," Ying said.

Point-of-use treatment options range from oxidation and precipitation filters to water softeners, chlorination, and reverse osmosis systems. But devices for monitoring water quality can cost up to $400 annually, and treatments for manganese-tainted water are just as expensive.

"It is possible to purchase filters for manganese, but a lot of people cannot afford them. We are hoping people in these communities can be subsidized to buy treatment options," Ying said.

Previously, the research team found that manganese-contaminated groundwater tends to occur in relatively shallow depths, compared to arsenic. They wondered if digging deeper wells would avoid the manganese contamination. Unfortunately, that strategy is unlikely to be effective.

"Using existing groundwater model predictions of manganese concentrations at deeper depths did not change the number of wells likely to be contaminated," Ying said.

The conditions that cause arsenic and manganese to leach are similar, so they tend to show up in groundwater in tandem. Arsenic has long been regulated as a primary contaminant in the U.S. "Wells are labeled unsafe if they contain arsenic, but not if they contain manganese," Ying said. "Thus, the number of wells considered safe may be greatly overestimated."

Furthermore, the researchers used a benchmark of 300 parts per billion of manganese to assess water quality. This is a level of manganese contamination that some studies have associated with neurological development issues, particularly for fetuses and infants during early growth periods. It is likely though that adverse effects can occur at lower levels.

"New studies from Canada, where manganese is now a primary contaminant, show there may be effects at 100 parts per billion," Ying said. "We were being conservative at 300."

This study focused on the Central Valley in part because the conditions that cause manganese to move from aquifer materials into water are so prevalent there. It is likely that drinking water from wells in other parts of the state is similarly tainted. Over 1.3 million Californians rely on unmonitored private wells.

"The population being exposed is much bigger than we might think. There are a lot of communities statewide drinking from private wells," Ying said.

Journal Reference:

  1. Miranda L. Aiken, Clare E. Pace, Maithili Ramachandran, Kurt A. Schwabe, Hoori Ajami, Bruce G. Link, Samantha C. Ying. Disparities in Drinking Water Manganese Concentrations in Domestic Wells and Community Water Systems in the Central Valley, CA, USAEnvironmental Science & Technology, 2023; 57 (5): 1987 DOI: 10.1021/acs.est.2c08548

Non-drug interventions for patients with Alzheimer's are both effective and cost-effective

 While new drugs to treat Alzheimer's disease tend to receive the most public attention, many well-researched ways to care for people with dementia don't involve medication. A new evaluation compared the cost-effectiveness of four non-drug interventions to the usual care received by people with dementia and found that the interventions not only resulted in a better quality of life, but also saved money.

In a study published April 6 in Alzheimer's & Dementia: The Journal of the Alzheimer's Association, researchers used a computer simulation model to show that the four dementia-care interventions saved between $2,800 and $13,000 in societal costs, depending on the type of intervention, and all reduced nursing home admissions and improved quality of life compared to usual care.

Alzheimer's drugs hold great promise, but they still need additional research and improvement, said lead study author Eric Jutkowitz, an associate professor at Brown University's School of Public Health. In the meantime, he said, a number of non-drug interventions have been shown to be effective in clinical trials in improving quality of life for people with dementia and helping them stay safely at home longer.

"Now that we can show that these effective interventions can also save money, it just makes sense to find ways to make them available to more families," Jutkowitz said. "These interventions can be used to help people with dementia starting today."

The four interventions studied included the following: Maximizing Independence at Home, an at-home, care coordination intervention that consists of care planning, skill-building, referrals to services and care monitoring; New York University Caregiver, which is implemented in an outpatient clinic and provides caregivers with six counseling sessions over four months plus lifetime ad-hoc support and access to weekly support groups; Alzheimer's and Dementia Care, in which a health care system provides people living with dementia and their caregivers a needs assessment, individual care plans and round-the-clock access to a care manager; and Adult Day Service Plus, which augments adult day care services with staff providing face-to-face caregiver support, disease education, care management, skill-building and resource referrals.

Nonpharmacological interventions like these provide family caregivers with knowledge, skills and support tailored to their care challenges. They have been shown to improve quality of life for the caregiver and the person living with dementia, as well as to reduce nursing home admissions, and they are not associated with adverse events such as hospitalizations and mortality. For these reasons, nonpharmacological interventions are recommended as first-line therapies for the management of Alzheimer's and dementia.

While non-drug interventions are well-studied, Jutkowitz said they haven't been widely implemented in clinical care centers. He added that there isn't currently an infrastructure in place to support these methods of care -- for example, there are limited mechanisms for providers to be reimbursed for these types of interventions.

To conduct the study, the researchers used a computer simulation to model the likelihood of nursing home admission for four evidence-based Alzheimer's and dementia nonpharmacological interventions compared to usual care. For each, the study evaluated societal costs, quality-adjusted life-years and cost-effectiveness. The inputs in the simulation were based on data from Medicare, clinical trials and national surveys with families of people with dementia.

Jutkowitz noted that the researchers benefited not only from Brown University computing resources that could handle intensive analytic tasks, but also access to data from the government's Centers for Medicare and Medicaid Services, which was crucial to the analysis.

In addition to finding that the interventions were cost-effective from a societal perspective, the researchers also found that from a health care payer perspective, the interventions involved little to no additional cost, compared to usual care, while increasing patient quality of life.

Based on the study findings, the authors concluded that health insurance policies should find ways to incentivize providers and health systems to implement nonpharmacological interventions.

The importance of understanding the cost-effectiveness of non-drug Alzheimer's and dementia interventions is further highlighted by changes in Medicare payment models and emerging Alzheimer's therapeutics, the researchers noted. The Centers for Medicare and Medicaid Services is in the process of determining coverage for new Alzheimer's and related dementia drugs.

"As the Centers for Medicare and Medicaid Services determine coverage for new Alzheimer's and related dementia drugs, we strongly believe that CMS should also consider the benefits of nonpharmacologic interventions," Jutkowitz said.

While this study focused on non-drug interventions that reduce nursing home admissions, a future analysis will look at similar interventions that reduce or maintain functional decline and challenging behaviors. The researchers are also working on designing a trial that would test the interventions with patients in a health care setting.

Additional Brown contributors included Peter Shewmaker and Gary Epstein-Lubow.

This research was supported by the National Institute on Aging (1R21AG059623-01, 1R01AG060871-01, 1RF1AG069771, R01AG049692).

Journal Reference:

  1. Eric Jutkowitz, Laura T. Pizzi, Peter Shewmaker, Fernando Alarid‐Escudero, Gary Epstein‐Lubow, Katherine M. Prioli, Joseph E. Gaugler, Laura N. Gitlin. Cost effectiveness of non‐drug interventions that reduce nursing home admissions for people living with dementiaAlzheimer's & Dementia, 2023; DOI: 10.1002/alz.12964