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New A.L.S. Treatment Lacks Evidence of Benefit, F.D.A. Panel Finds

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The first objective was to gradual decline on a 48-point A.L.S. scale ranking 12 bodily talents, together with strolling, talking, swallowing, dressing, handwriting and respiratory. Over 24 weeks, sufferers receiving a placebo declined 2.32 factors greater than these taking the drug mixture, which translated to a 25 % slower decline throughout that point for sufferers receiving the remedy.

The open-label extension research concerned 90 of these sufferers, together with 34 from the placebo group, who started taking AMX0035 about seven months after those that had obtained it from the start. The researchers reported to the F.D.A. that those that obtained the remedy the longest had a median of 4.8 months extra time earlier than being hospitalized, being placed on a ventilator or dying.

“That is the primary time that we’ve seen a profit in each perform and survival in an A.L.S. medical trial,” mentioned Dr. Sabrina Paganoni, the principal investigator of the medical trial and a neuromuscular drugs specialist at Massachusetts Normal Hospital’s Healey Heart for A.L.S.

“If entry is delayed, the sufferers in my clinic right now might by no means obtain the time and performance that they may have had. Delaying entry shouldn’t be a threat that we should always take,” Dr. Paganoni mentioned.

F.D.A. reviewers, nonetheless, recognized many points with each the Section 2 medical trial and the open-label extension. They mentioned in briefing paperwork that the profit recognized was “borderline statistically important and might not be sufficiently persuasive to permit an effectiveness willpower based mostly on a single research.”

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Dr. Emily Freilich, a frontrunner of the F.D.A. staff, mentioned on the listening to that the medical trial outcomes suggesting that the drug slowed decline on the A.L.S. useful scale had been “not extremely persuasive” and that the trial’s secondary measures — together with muscle energy, respiratory means and whether or not sufferers had been hospitalized — had been “not usually supportive” of profit.

F.D.A. officers mentioned that the proof, even from the extension research, doesn’t show that the remedy will help sufferers reside longer. Dr. Freilich mentioned that sufferers who obtained the placebo and by no means switched to AMX0035 survived for a median of 1,295 days, whereas sufferers who obtained AMX0035 for longer than 96 weeks survived for a median of 1,237 days.

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Signs of avian flu found in San Francisco wastewater

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Signs of avian flu found in San Francisco wastewater

Signs of H5N1 bird flu virus have been detected at three wastewater sites in California’s Bay Area, according to sampling data.

While positive wastewater samples have been found in seven other states, California is the only one that has yet to report a bird flu outbreak in a herd of dairy cows.

Genetic evidence of bird flu was detected in San Francisco wastewater on June 18 and June 26. Additional H5 “hits” were seen at a site in Palo Alto on June 19, and another on June 10 from the West County Wastewater facility in Richmond.

According to the San Francisco Department of Public Health, officials have been closely monitoring H5N1 along with federal, state and local partners, and are “aware of the recent detections of fragments of H5N1 in San Francisco’s wastewater.”

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“As with the previous detections reported from before mid-May 2024, it is unclear what the source of H5N1 is, and an investigation is ongoing,” wrote department officials in a statement. “It is possible that it originated from bird waste or waste from other animals due to San Francisco’s sewer system that collects and treats both wastewater and stormwater in the same network of pipes.”

Health officials said the risk remains low for the general public.

The virus has not been identified in California cows, but it has been found in wild birds and domestic poultry in the state.

The finding “is concerning” because of their urban origin, said Devabhaktuni Srikrishna, an entrepreneur who is developing techniques for disease detection, and the chief executive and founder of PatientKnowHow.com. “There are not many dairy or animal farms in San Francisco.”

There are also no dairy farms in Palo Alto or Richmond.

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The plant manager from Palo Alto was out of the office Friday, so could not comment. A spokesperson for the Richmond site directed questions to the state.

A request for comment from the state’s Wastewater Surveillance Program had not yet been returned.

Although the samples from the Bay Area wastewater sites tested positive for H5, the testing was not specific to H5N1.

However, researchers say a positive genetic identification for H5 is suggestive of bird flu — whether H5N1, the virus that has been found in U.S. dairy cattle (and which has infected three dairy workers ) or H5N2, the subtype implicated in the death of a man from Mexico City this month.

Most human influenza A viruses are of the H1 and H3 variety.

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The virus has been detected in 133 dairy herds across 12 states. It has also been found in wild birds and domestic poultry flocks throughout the United States.

In recent weeks, H5 was also detected in wastewater samples in Idaho. among other states.

While there is “no threat to the general public from the H5 detection in wastewater” at this time, said Christine Hahn, Idaho state epidemiologist, “we have determined that it is important that we work to understand these recent findings as much as possible.”

The state is working in conjunction with the Centers for Disease Control and Prevention to investigate the issue.

WastewaterSCAN, the research organization that detected the virus, is an infectious disease monitoring network run by researchers at Stanford, Emory University and Verily, Alphabet Inc.’s life sciences organization.

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A review of their data — which samples from 194 locations across the country — suggests H5 has also been detected at sites in Michigan, Texas, Minnesota, South Dakota and Iowa.

California is the only one of these states that has not reported H5N1-infected cattle.

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One of Earth's oldest known plants takes center stage in California development battle

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One of Earth's oldest known plants takes center stage in California development battle

A Palmer oak in Jurupa Valley is estimated to be 13,000 to 18,000 years old. The plant, which looks like a sprawling, dark green shrub, is now at the center of a development battle.

(Aaron Echols)

After a contentious five-hour public meeting, environmentalists advocates have persuaded Inland Empire officials to delay development of a project within 400 feet of one of the oldest known plants in the state and the third-oldest in the world.

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“Tonight has been a real learning process,” Jurupa Valley City Planning Commission Chair Penny Newman said at the Thursday meeting. “I think we all need time to process the information we’ve had here tonight.”

The commission voted unanimously to table the vote. Commissioners said the developers must do more studies into the potential effects on the plant, a Palmer oak, and further explore protective measures. Commissioners also requested more details on a plan to transfer ownership of the tree and surrounding land to a local tribe, who would oversee its conservation.

“We have discovered a treasure on the world stage here in our humble city,” lifelong Jurupa Valley resident Jennifer Iyer said at the meeting. “In a city known for its toxic waste dump, the worst air quality in the nation … let’s have a plan that protects and celebrates something unique that makes us proud.”

The roughly 370-acre development would include residential housing, an elementary school, a business park and industrial buildings. It would leave the tree on a 27-acre rocky outcrop, but it would come within 400 feet of the plant. Scientists and tribal members say the oak has been around for at least 13,000 years — surviving the last ice age and, more recently, the founding of the United States.

Members of the Shiishongna Tongva Nation, the Corona Band Of Gabrieleño Indians and the Kizh Nation, Gabrieleño Band Of Mission Indians have lived in the Santa Ana River Basin for millennia as well. Both groups regard the tree as sacred.

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“We’ve known about this tree forever,” said Michael Negrete, chief and chairperson of the Shiishongna Tongva Nation. “It gives medicine. It gives oxygen. It gives life to the animals.”

Companies have been trying to develop the land since the early 1990s, with Richland Communities presenting the current plan in 2019. After discussions with the City Planning Commission and the public, it has replaced potential warehouses with light industrial space and a business park, increased the amount of open space, and committed to transfer ownership and conservation responsibilities of the land with the Palmer oak to a Native tribe or conservation organization.

Richland Communities announced at the meeting that it had reached an agreement in concept to transfer the land to the Kizh Nation and provide them with a $250,000 initial endowment for conservation. Company executives also proposed requiring the agreement to be finalized before construction begins on the industrial and business sections, which are closest to the tree.

Commissioners want additional information on the plan’s details and how conservation of the land would be legally enforced. Richland Communities did not respond to a request for comment.

Compared to rugged California live oaks, the Palmer oak looks more like a shrub and is made up of individual stems sprouting in a grove. It wasn’t until fairly recently that researchers determined its impressive age.

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Mitchell Provance, a botanist and associate researcher at UC Riverside, first noticed the oak more than two decades ago and found it odd that it lived isolated from other members of its species in an area that was much lower and hotter than where the trees usually grow. He began discussing the tree with his colleagues. They hypothesized that it was the last holdout from a time when the region was cooler and wetter — a much friendlier environment for the oaks.

To see if this was the case, the researchers collected samples from multiple dead stems —and, sure enough, they all had identical DNA. Whenever the tree was damaged by a fire, it would resprout from the base of its trunk. By using tree rings to estimate how much the trunk can grow in a year, the team was able to calculate the tree’s age by measuring the grove’s diameter.

Today, the grove measures 80 feet wide, which led researchers to estimate that the tree is between 13,000 and 18,000 years old. It’s possible that the tree has been able to reproduce with itself, instead of just resprouting from the trunk to produce clones, but this is unlikely, experts say.

While the company has worked with the environmental consultant FirstCarbon Solutions to study the impact of construction vibrations on the tree and identify potential water sources, it has not mapped the tree’s root system or confirmed its direct water source — a process that would involve chemical testing of water at the oak’s roots.

Some also worry the proposed development would expose the aged oak to the urban heat island effect — a phenomenon in which developed areas can run 1 to 7 degrees higher than shaded, natural areas during the day.

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Aaron Echols, the conservation chair of the Riverside/San Bernardino California Native Plants Society, said it was the duty of conservation groups to point out potential effects on the tree that haven’t yet been studied. “The burden to mitigate impacts … that’s on the applicant and the consultant.”

Aaron Echols walks along a dirt path in a canyon where the Palmer's Oak is located in Jurupa Valley.

Environmentalist Aaron Echols walks along a dirt path across from a giant hill where the Palmer oak is located. The development would extend up to the base of the hill.

(Gina Ferazzi / Los Angeles Times)

The portion of the environmental impact review discussing the Palmer oak — including its exact location — has been redacted from public documents. The city was required to do this by law, since the tree has sensitive cultural significance to the Native tribes. Consequently, independent scientists have been unable to scrutinize the report.

The city said it would explore “creative ways” to legally allow a select few third-party experts to view and discuss the report.

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Is bird flu in cattle here to stay?

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Is bird flu in cattle here to stay?

Despite assurances from the federal government that bird flu will be eradicated from the nation’s dairy cows, some experts worry the disease is here to stay.

Recently, Eric Deeble, USDA acting senior advisor for H5N1 response, said that the federal government hoped to “eliminate the disease from the dairy herd” without requiring vaccines.

Since the disease was first publicly identified in dairy cattle on March 25, there have been 129 reports of infected herds across 12 states. In the last four weeks, there has been a surge — jumping from 68 confirmed cases on May 28 to nearly twice that many as of June 25. There are no cases in California.

So far, however, the dairy industry has proved reluctant to work with state and federal governments to allow for widespread testing of herds.

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To some epidemiologists, this lack of close herd surveillance is a problem. They worry that the virus is spreading unchecked among dairy cows and other animals, and has taken up permanent residence.

David Topham, a professor of microbiology and immunology at the University of Rochester’s Center for Vaccine Biology and Immunology, said he considers H5N1 to be “endemic in animals in North America” — citing its prevalence in wild bird populations as well as its long staying power in domestic poultry.

No one knows how widespread it is in cattle, Topham said, because testing has largely targeted symptomatic cows and herds. “But I suspect the closer we look, the more we’ll find, and I don’t know if we’re going to cull our entire cattle herds and start over again.”

Topham said he understands the industry’s reluctance to permit government scientists onto farms “because we’re going to want to see everything, and we’re going to report everything that we see, and that might be bad for business. … But until we have all that information, I don’t think we will have control.”

Federal officials have announced a pilot bulk milk testing program that includes Kansas, Nebraska, New Mexico and Texas. Farmers in these states can voluntarily enroll to have bulk milk samples tested for the virus. If their samples test negative for three weeks, they will be able to move their herds across state lines without additional testing — something they are currently unable to do.

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So far, only one herd in each state has signed up.

A USDA “strike force” investigated 15 infected Michigan dairy herds as well as eight turkey flocks in early April. It worked with the state of Michigan as well as individual farmers.

The investigation was launched after local researchers identified a “spillover” event that went from infected cattle to a nearby poultry plant. The state — and farmers — wanted to know how it happened.

What the team found suggests the “control” Topham referred to may be elusive.

From surveys and observations, they found that cats and chickens were free to walk around without containment — potentially migrating between nearby dairies and poultry farms. Some of these animals had become infected; several died.

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Asked about their practices regarding isolation of newly introduced cattle, three out of 14 farms said they always isolated, another three said they never isolated, and the remainder didn’t respond.

Then there was the dumping of unpasteurized, contaminated milk into the open waste lagoons on several of the farms. And the feeding of non-pasteurized milk to calves on three farms. Or the potentially contaminated manure that was stored, composted or applied to nearby fields. In one case, a farmer reported they had sold or given away potentially contaminated manure.

Finally there was the issue of humans: On every farm, there were visitors, carcass removal companies, milk suppliers, veterinarians and employees — many of whom traveled between farms.

For instance, of the 14 dairies that reported information about their employees, three had employees that worked at other dairies, one had employees that worked at a poultry farm, and one had an employee who also worked at a swine farm. At four dairies, some of the employees were reported to have their own livestock at home.

As the authors reported, “transmission between farms is likely due to indirect epidemiological links related to normal business operations … with many of these indirect links shared between premises.”

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They noted there was no evidence to suggest waterfowl had introduced the virus to the Michigan herds.

Michael Payne, researcher and outreach coordinator at UC Davis’ School of Veterinary Medicine Western Institute for Food Safety and Security, said there was no one to blame for the lack of containment.

He said in the weeks and months before the disease was identified in cattle, researchers from across the nation scrambled to figure out what was happening to dairy cows in Texas that appeared listless and had diminished milk production.

“It’s not like people weren’t aware or concerned and trying to figure it out,” he said. And then once it was identified, and it didn’t seem to cause too much illness in cows or transfer to humans quickly, while there was urgency, the system fell into a series of “incremental” solutions — negotiated among dozens of federal and state agencies.

He and Topham agree that no one can say for sure what the virus will do — and where it will go — next.

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If it becomes endemic in cattle and is renamed “bovine influenza,” vaccines are likely to follow, as well as continuous surveillance and testing of dairy products.

Topham said that the biggest concern among epidemiologists now is how the virus will evolve as it continues to move — largely unabated and undetected — through cattle herds, resident farm animals and people.

There have been three human cases of H5N1 in U.S. dairy workers since March.

One key worry is that the virus may move with a dairy employee onto a small farm and then recombine inside a pig, dog or cat that is harboring another flu virus.

He and Payne agree that officials need to remain alert to signs that the virus is adapting in ways that could hurt humans.

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Wastewater is one way to detect the location of the virus.

As of Tuesday, data from the academic research organization WastewaterSCAN show that levels of H5 influenza have been rising in wastewater samples from a facility in Boise, Idaho.

Asked about whether the region’s health department was investigating, or if there was any idea where the H5 was coming from, Surabhi Malesha, communicable disease program manager at Central District Health in Idaho, said there was no way to know if the H5 signal was from H5N1 or another influenza subtype.

She said testing for H5 in wastewater had only recently started and therefore “there is no way to compare this data from last year or the year before, and so we don’t know what a baseline detection of H5 looks like.”

“Maybe we see H5 detections like this on a regular basis, and it is not of public health significance or importance. … How do we define normalcy when we have nothing to compare the data to?”

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She said the findings were “not a public health concern” and her agency and the state “do not need to really investigate into this, because this could be H5N1, or could be any other H5 strains, and it really does not affect the public in general.”

Dennis Nash, distinguished professor of epidemiology and executive director of City University of New York’s Institute for Implementation Science in Population Health, said that given the current situation, the wastewater sample should be considered H5N1 “until proven otherwise. The only other H5 we know about is H5N2. And a man in Mexico City just died from that.”

Nash said health officials should be trying to determine the source of the virus found in the wastewater: a nearby dairy herd, a milk processing site or raw milk that was dumped down the drain.

Idaho has reported 27 infected herds, although according to Malesha, none has been reported in the Central District.

“You want to do everything you can to prevent these types of viruses from emerging, because once they do, we don’t have a whole lot of control over them,” Topham said. “Because when the horse is out of the barn, it’s gone. So I think the question is, what do we need to do to keep this in check?”

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