scientificamerican--2020-10-23--Funky Cheese Rinds Release an Influential Stench

Aged cheeses like camembert or taleggio produce a powerful stench : the funk of cabbage , mushrooms , sulfur , even smelly feet .
`` And those aromas are chemicals that are being kicked off , being emitted by the cheese , and that 's through the microbes that are living in the rind , as they slowly decompose the cheese . ''
Benjamin Wolfe is a microbiologist at Tufts University .
He says , in addition to alerting our noses to the cheese , the aromas produced by certain microbes living in and on the cheese can feed and @ @ @ @ @ @ @ living on the cheese .
Wolfe and his colleagues identified the microbial interactions by growing various cheese-dwelling fungi and bacteria in separate but adjacent dishes in the lab .
The microbes could n't touch—they could interact only via the volatile compounds they released .
`` When we did this screen we quickly noticed there was this one bacterium , a Vibrio species , that really loved living in the aromas produced by the various fungi that you find in a typical wheel of camembert . ''
Wolfe says the Vibrio bacteria may be @ @ @ @ @ @ @ after all , consist of chemical compounds .
And the odor of the cheese may also switch on certain genetic pathways in the bacteria—pathways that regulate the bacteria 's ability to thrive in harsh conditions .
`` It 's a backup plan when things are n't going well and you 're starving , you can turn on this other pathway and still make a living , but on these less ideal substrates that are around . ''
The end result is that the stench we perceive may also shape the microbiome of the @ @ @ @ @ @ @ journal Environmental Microbiology .
[ Casey M. Cosetta et al , Fungal volatiles mediate cheese rind microbiome assembly ] As for the practical outcomes of this research—well , it 's a little early for that .
`` We do n't necessarily do our science to make cheese better .
Honestly , a lot of it is to figure out how cheese works . ''
In other words , he says , the tools of modern microbiology allow scientists to finally listen in to the conversations happening in these tiny cheese rind communities .
@ @ @ @ @ @ @ of this podcast . ]

Full Transcript
Aged cheeses like Camembert or Taleggio produce a powerful stench: the funk of cabbage, mushrooms, sulfur, even smelly feet.
“And those aromas are chemicals that are being kicked off, being emitted by the cheese, and that’s through the microbes that are living in the rind, as they slowly decompose the cheese.”
Benjamin Wolfe is a microbiologist at Tufts University. He says in addition to alerting our noses to the cheese, the aromas produced by certain microbes living in and on the cheese can feed and sculpt other members of the microbial garden living on the cheese.
Wolfe and his colleagues identified the microbial interactions by growing various cheese-dwelling fungi and bacteria in separate but adjacent dishes in the lab. The microbes couldn’t touch—they could interact only via the volatile compounds they released.
“When we did this screen, we quickly noticed there was this one bacterium, a Vibrio species, that really loved living in the aromas produced by the various fungi that you find in a typical wheel of camembert.”
Wolfe says the Vibrio bacteria may be able to actually eat the aromas—which, after all, consist of chemical compounds. And the odor of the cheese may also switch on certain genetic pathways in the bacteria—pathways that regulate the bacteria’s ability to thrive in harsh conditions.
“It’s a backup plan: when things aren’t going well, and you’re starving, you can turn on this other pathway and still make a living but on these less ideal substrates that are around.”
The end result is that the stench we perceive may also shape the microbiome of the cheese. The results appear in the journal Environmental Microbiology. [Casey M. Cosetta et al., Fungal volatiles mediate cheese rind microbiome assembly]
As for the practical outcomes of this research—well, it’s a little early for that.
“We don’t necessarily do our science to make cheese better. Honestly, a lot of it is to figure out how cheese works.”
In other words, he says, the tools of modern microbiology allow scientists to finally listen in to the conversations happening in these tiny cheese-rind communities.
—Christopher Intagliata
[The above text is a transcript of this podcast.]


scientificamerican--2020-10-22--Coronavirus Drug Remdesivir Shortens Recovery but Is Not a Magic Bullet

Editor ’ s Note ( 10/22/20 ) : The U.S. Food and Drug Administration approved remdesivir today for adults and children 12 years and older who weigh at least 40 kilograms .
It is the first approved treatment for COVID-19 in the U.S. An experimental drug—and one of the world ’ s best hopes against COVID-19—could shorten the time to recovery from coronavirus infection , according to the largest and most rigorous clinical trial of the compound .
The experimental drug , called remdesivir , interferes with replication of some viruses , including the SARS-CoV-2 virus responsible for the current @ @ @ @ @ @ @ Fauci , director of the US National Institute of Allergy and Infectious Disease ( NIAID ) , announced that a clinical trial of more than a thousand people showed that people taking remdesivir recovered in 11 days on average , compared to 15 days for those on a placebo .
“ Although a 31 % improvement doesn ’ t seem like a knockout 100 % , it is a very important proof of concept , ” Fauci said .
“ What it has proven is that a drug can block this virus.
” @ @ @ @ @ @ @ who received the drug , he said , but that trend was not statistically significant .
The shortened recovery time , however , was significant , and was enough of a benefit that investigators decided to stop the trial early for ethical reasons , he said , to ensure that those participants who were receiving placebo could now access the drug .
Fauci added that remdesivir would become a standard treatment for COVID-19 .
The news comes after weeks of data leaks and on a day of mixed results from clinical trials of @ @ @ @ @ @ @ by the drug ’ s maker , Gilead Sciences of Foster City , California , more than half of 400 participants with severe COVID-19 recovered from their illness within two weeks of receiving treatment .
But the study lacked a placebo controlled arm , making the results difficult to interpret .
Another smaller trial run in China found no benefits from remdesivir when compared with a placebo .
But the trial was stopped early due to the difficulty in enroling participants as the outbreak subsided in China .
Nevertheless , onlookers are hopeful @ @ @ @ @ @ @ first glimmer of hope in a race to find a drug that works against the coronavirus , which has infected more than 3 million people worldwide .
“ There is a lot of focus on remdesivir because it ’ s potentially the best shot we have , ” says virologist Stephen Griffin at the University of Leeds in the UK .
The fast-flowing , conflicting information on remdesivir has left people reeling over the past weeks .
In the rush to find therapies to combat COVID-19 , small , clinical trials without control @ @ @ @ @ @ @ ’ m just very annoyed by all of these non-controlled studies , ” says Geoffrey Porges , an analyst for the investment bank SVB Leerink in New York City .
“ It ’ s reassuring that 50–60 % of patients are discharged from the hospital , but this is a disease that mostly gets better anyway.
” With so much uncertainty , the remdesivir-watchers were waiting anxiously for final results from the NIAID trial , which were not expected until the end of May .
In lieu of a vaccine , which could @ @ @ @ @ @ @ , effective therapies are critical to reducing deaths and limiting economic damage from the pandemic .
Yet , despite the flood of small clinical trials , no therapy has been convincingly shown to boost survival in people with COVID-19 .
The NIAID results put a new sheen on remdesivir .
“ It may not be the wonder drug that everyone ’ s looking for , but if you can stop some patients from becoming critically ill , that ’ s good enough , ” says Griffin .
Fauci said the finding reminded him @ @ @ @ @ @ @ the drug AZT helped to combat HIV infection .
The first randomized , controlled clinical only showed a modest improvement , he said , but researchers continued to build on that success , eventually developing highly effective therapies .
For now , he said , remdesivir would become a standard treatment for COVID-19 .
Remdesivir works by gumming up an enzyme that some viruses , including SARS-CoV-2 , use to replicate .
In February , researchers showed that the drug reduces viral infection in human cells grown in a laboratory .
Gilead began @ @ @ @ @ @ @ before the NIAID results .
By the end of March , the company had produced enough to treat 30,000 patients .
By streamlining its manufacturing process and finding new sources of raw materials , Gilead announced that it hoped to produce enough remdesivir to treat more than a million people by the end of the year .
That calculation was based on the assumption that people would take the drug for 10 days , but the results announced from Gilead ’ s trial today suggest that a 5-day course of treatment could work @ @ @ @ @ @ @ that would effectively double the number of people who could be treated , says Porges .
In the long term , clinicians will likely want a bevy of anti-viral drugs—with different ways of disabling the virus—in their arsenal , says Timothy Sheahan , a virologist at the University of North Carolina in Chapel Hill , who has teamed up with Gilead researchers to study remdesivir .
“ There is always the potential for antiviral resistance , ” he says .
“ And to hedge against that potential , it ’ s good to @ @ @ @ @ @ @ also a second- , third- , fourth- , fifth-line antiviral.
” Researchers are furiously testing a wide range of therapies , but early results , while not yet definitive , have not been encouraging .
The malaria drugs chloroquine and hydroxychloroquine , both of which also have anti-inflammatory effects , drew so much attention from physicians and the public that some countries have depleted their supplies of the drugs .
Yet studies in humans have failed to show a consistent benefit , and some have highlighted the risks posed by side effects of @ @ @ @ @ @ @ interest in a mix of two HIV drugs called lopinavir and ritonavir flagged when a clinical trial in nearly 200 people did not find any benefit of the mix for those with severe COVID-19 .
Another promising therapeutic hypothesis—that inhibiting the action of an immune system regulator called IL-6 could reduce the severe inflammation seen in some people with severe COVID-19—has met with mixed results thus far .
Still , a host of other therapies are being tested in people , and many researchers are hunting for new drugs at the bench .
@ @ @ @ @ @ @ compound that is active against SARS-CoV-2 and other coronaviruses , including a remdesivir-resistant variant of a coronavirus , when tested in laboratory-grown human cells .
But much more testing would need to be done before the compound could be tried in people .
“ What we ’ re doing now will hopefully have an impact on the current pandemic , ” he says .
“ But maybe more importantly , it could position us to better respond more quickly in the future.
” This article is reproduced with permission and was first published @ @ @ @ @ @ @ about the coronavirus outbreak here .

Editor’s Note (10/22/20): The U.S. Food and Drug Administration approved remdesivir today for adults and children 12 years and older who weigh at least 40 kilograms. It is the first approved treatment for COVID-19 in the U.S.
An experimental drug—and one of the world’s best hopes against COVID-19—could shorten the time to recovery from coronavirus infection, according to the largest and most rigorous clinical trial of the compound.
The experimental drug, called remdesivir, interferes with replication of some viruses, including the SARS-CoV-2 virus responsible for the current pandemic. On 29 April, Anthony Fauci, director of the US National Institute of Allergy and Infectious Disease (NIAID), announced that a clinical trial of more than a thousand people showed that people taking remdesivir recovered in 11 days on average, compared to 15 days for those on a placebo.
“Although a 31% improvement doesn’t seem like a knockout 100%, it is a very important proof of concept,” Fauci said. “What it has proven is that a drug can block this virus.”
Deaths were also lower in trial participants who received the drug, he said, but that trend was not statistically significant. The shortened recovery time, however, was significant, and was enough of a benefit that investigators decided to stop the trial early for ethical reasons, he said, to ensure that those participants who were receiving placebo could now access the drug. Fauci added that remdesivir would become a standard treatment for COVID-19.
The news comes after weeks of data leaks and on a day of mixed results from clinical trials of the drug. In a trial run by the drug’s maker, Gilead Sciences of Foster City, California, more than half of 400 participants with severe COVID-19 recovered from their illness within two weeks of receiving treatment. But the study lacked a placebo controlled arm, making the results difficult to interpret. Another smaller trial run in China found no benefits from remdesivir when compared with a placebo. But the trial was stopped early due to the difficulty in enroling participants as the outbreak subsided in China. Nevertheless, onlookers are hopeful that the large NIAID trial provides the first glimmer of hope in a race to find a drug that works against the coronavirus, which has infected more than 3 million people worldwide.
“There is a lot of focus on remdesivir because it’s potentially the best shot we have,” says virologist Stephen Griffin at the University of Leeds in the UK.
Small trials
The fast-flowing, conflicting information on remdesivir has left people reeling over the past weeks. In the rush to find therapies to combat COVID-19, small, clinical trials without control groups have been common. “I’m just very annoyed by all of these non-controlled studies,” says Geoffrey Porges, an analyst for the investment bank SVB Leerink in New York City. “It’s reassuring that 50–60% of patients are discharged from the hospital, but this is a disease that mostly gets better anyway.”
With so much uncertainty, the remdesivir-watchers were waiting anxiously for final results from the NIAID trial, which were not expected until the end of May. In lieu of a vaccine, which could still be more than a year away, effective therapies are critical to reducing deaths and limiting economic damage from the pandemic. Yet, despite the flood of small clinical trials, no therapy has been convincingly shown to boost survival in people with COVID-19.
The NIAID results put a new sheen on remdesivir. “It may not be the wonder drug that everyone’s looking for, but if you can stop some patients from becoming critically ill, that’s good enough,” says Griffin.
Fauci said the finding reminded him of the discovery in the 1980s that the drug AZT helped to combat HIV infection. The first randomized, controlled clinical only showed a modest improvement, he said, but researchers continued to build on that success, eventually developing highly effective therapies. For now, he said, remdesivir would become a standard treatment for COVID-19.
Remdesivir works by gumming up an enzyme that some viruses, including SARS-CoV-2, use to replicate. In February, researchers showed that the drug reduces viral infection in human cells grown in a laboratory.
Gilead began to ramp up production of remdesivir well before the NIAID results. By the end of March, the company had produced enough to treat 30,000 patients. By streamlining its manufacturing process and finding new sources of raw materials, Gilead announced that it hoped to produce enough remdesivir to treat more than a million people by the end of the year.
That calculation was based on the assumption that people would take the drug for 10 days, but the results announced from Gilead’s trial today suggest that a 5-day course of treatment could work just as well. If so, that would effectively double the number of people who could be treated, says Porges.
Many drugs needed
In the long term, clinicians will likely want a bevy of anti-viral drugs—with different ways of disabling the virus—in their arsenal, says Timothy Sheahan, a virologist at the University of North Carolina in Chapel Hill, who has teamed up with Gilead researchers to study remdesivir. “There is always the potential for antiviral resistance,” he says. “And to hedge against that potential, it’s good to have not only a first-line, but also a second-, third-, fourth-, fifth-line antiviral.”
Researchers are furiously testing a wide range of therapies, but early results, while not yet definitive, have not been encouraging. The malaria drugs chloroquine and hydroxychloroquine, both of which also have anti-inflammatory effects, drew so much attention from physicians and the public that some countries have depleted their supplies of the drugs. Yet studies in humans have failed to show a consistent benefit, and some have highlighted the risks posed by side effects of the drugs on the heart.
Early interest in a mix of two HIV drugs called lopinavir and ritonavir flagged when a clinical trial in nearly 200 people did not find any benefit of the mix for those with severe COVID-19. Another promising therapeutic hypothesis—that inhibiting the action of an immune system regulator called IL-6 could reduce the severe inflammation seen in some people with severe COVID-19—has met with mixed results thus far.
Still, a host of other therapies are being tested in people, and many researchers are hunting for new drugs at the bench. Sheahan and his colleagues have found a compound that is active against SARS-CoV-2 and other coronaviruses, including a remdesivir-resistant variant of a coronavirus, when tested in laboratory-grown human cells.
But much more testing would need to be done before the compound could be tried in people. “What we’re doing now will hopefully have an impact on the current pandemic,” he says. “But maybe more importantly, it could position us to better respond more quickly in the future.”
This article is reproduced with permission and was first published on April 29 2020.
Read more about the coronavirus outbreak here.


scientificamerican--2020-10-22--AI Assesses Alzheimer's Risk by Analyzing Word Usage

Artificial intelligence could soon help screen for Alzheimer ’ s disease by analyzing writing .
A team from IBM and Pfizer says it has trained AI models to spot early signs of the notoriously stealthy illness by looking at linguistic patterns in word usage .
Other researchers have already trained various models to look for signs of cognitive impairments , including Alzheimer ’ s , by using different types of data , such as brain scans and clinical test results .
But the latest work stands out because it used historical information from the multigenerational Framingham Heart Study , which @ @ @ @ @ @ @ than 14,000 people from three generations since 1948 .
If the new models ’ ability to pick up trends in such data holds up in forward-looking studies of bigger and more diverse populations , researchers say they could predict the development of Alzheimer ’ s a number of years before symptoms become severe enough for typical diagnostic methods to pick up .
And such a screening tool would not require invasive tests or scans .
The results of the Pfizer-funded and IBM-run study were published on Thursday in EClinicalMedicine .
The new AI @ @ @ @ @ @ @ practitioners in how you would see some subtle changes earlier in time , before the clinical diagnosis has been achieved , ” says Ajay Royyuru , vice president of health care and life sciences research at IBM .
“ It might actually alert you to some changes that [ indicate ] you ought to then go do a more complete exam.
” To train these models , the researchers used digital transcriptions of handwritten responses from Framingham Heart Study participants who were asked to describe a picture of a woman who is apparently @ @ @ @ @ @ @ raid a cookie jar behind her back .
These descriptions did not preserve the handwriting from the original responses , says Rhoda Au , director of neuropsychology at the Framingham study and a professor at Boston University .
( Her team was responsible for transcribing data for the new paper but did not participate beyond that . )
Yet even without the physical handwriting , IBM says its main AI model was able to detect linguistic features that are sometimes related to early signs of cognitive impairment .
They include certain misspellings , @ @ @ @ @ @ @ phrases rather than grammatically complex sentences .
This evidence is in line with clinicians ’ understanding of how Alzheimer ’ s disease can impact language , Royyuru says .
The main model achieved 70 percent accuracy in predicting which of the Framingham participants eventually developed dementia associated with Alzheimer ’ s disease before the age of 85 .
This result was based on historical data rather than actually predicting future events , however—and there are other caveats to the new paper as well .
The AI focused on the oldest group of Framingham @ @ @ @ @ @ @ non-Hispanic white population .
This limits how much the results can be generalized to more diverse communities in the U.S. and the rest of the world , Au notes .
It also remains unclear how the AI would perform in larger populations : the EClinicalMedicine study ’ s data set involved just 40 people who eventually developed dementia and 40 “ controls ” who did not , notes Jekaterina Novikova , director of machine learning at Winterlight Labs in Toronto .
Novikova , who was not involved in the new study , also @ @ @ @ @ @ @ s AI would change when predicting the onset of Alzheimer ’ s at different points in time prior to diagnosis .
Still , she and Au praise the paper as a solid contribution to the field that might draw more attention and resources to AI detection of Alzheimer ’ s .
“ What I like personally about the [ study ] is that it ’ s one of the very few works that analyzes the big-scale , real-life data that was collected over a very long period of time , ” Novikova says @ @ @ @ @ @ @ more accurate if it could have incorporated handwriting , Au suggests .
This ability could have provided additional clues , such as evidence of tiny tremors , switching between print and cursive , and very tiny letters .
“ There are a lot of ... features that [ the researchers ] did not account for , which , combined with linguistic features , would have probably created an even more predictive model , ” Au says .
The IBM models also did not include data from spoken language .
Using AI speech analysis @ @ @ @ @ @ @ growing area of research , and other systems have focused on detecting changes in audio samples .
These contain clues such as speech pauses , which are not found in writing .
Whether written or spoken , language samples offer a relatively noninvasive source of information for monitoring peoples ’ cognitive health , compared with brain scans and other laboratory tests .
Collecting such language data could be done cheaply and remotely—though doing so would still require strict informed consent and privacy safeguards for the individuals creating the samples , Royyuru says .
@ @ @ @ @ @ @ may not want to even know how likely they are to develop Alzheimer ’ s disease—a condition that is currently irreversible .
Training models on spoken rather than written samples might prove more practical for achieving the broadest reach in the long run , given that writing requires literacy while speech does not .
Novikova and her colleagues at Winterlight Labs have been focusing heavily on teaching AI to analyze the acoustic and linguistic characteristics in spoken words .
And Au has been recording both speech and handwriting , using digital pens to @ @ @ @ @ @ @ .
IBM seems to be thinking along the same lines for its own future work .
“ We are in the process of leveraging this technology to better understand diseases such as schizophrenia , [ amyotrophic lateral sclerosis ] and Parkinson 's disease and are doing so in prospective studies [ that ] analyze spoken speech samples , given with consent from similar cognitive verbal tests , ” says Guillermo Cecchi , a co-author of the new study and a principal researcher for computational psychiatry and neuroimaging at IBM .

Artificial intelligence could soon help screen for Alzheimer’s disease by analyzing writing. A team from IBM and Pfizer says it has trained AI models to spot early signs of the notoriously stealthy illness by looking at linguistic patterns in word usage.
Other researchers have already trained various models to look for signs of cognitive impairments, including Alzheimer’s, by using different types of data, such as brain scans and clinical test results. But the latest work stands out because it used historical information from the multigenerational Framingham Heart Study, which has been tracking the health of more than 14,000 people from three generations since 1948. If the new models’ ability to pick up trends in such data holds up in forward-looking studies of bigger and more diverse populations, researchers say they could predict the development of Alzheimer’s a number of years before symptoms become severe enough for typical diagnostic methods to pick up. And such a screening tool would not require invasive tests or scans. The results of the Pfizer-funded and IBM-run study were published on Thursday in EClinicalMedicine.
The new AI models provide “an augmentation to expert practitioners in how you would see some subtle changes earlier in time, before the clinical diagnosis has been achieved,” says Ajay Royyuru, vice president of health care and life sciences research at IBM. “It might actually alert you to some changes that [indicate] you ought to then go do a more complete exam.”
To train these models, the researchers used digital transcriptions of handwritten responses from Framingham Heart Study participants who were asked to describe a picture of a woman who is apparently preoccupied with washing dishes while two kids raid a cookie jar behind her back. These descriptions did not preserve the handwriting from the original responses, says Rhoda Au, director of neuropsychology at the Framingham study and a professor at Boston University. (Her team was responsible for transcribing data for the new paper but did not participate beyond that.) Yet even without the physical handwriting, IBM says its main AI model was able to detect linguistic features that are sometimes related to early signs of cognitive impairment. They include certain misspellings, repeated words and the use of simplified phrases rather than grammatically complex sentences. This evidence is in line with clinicians’ understanding of how Alzheimer’s disease can impact language, Royyuru says.
The main model achieved 70 percent accuracy in predicting which of the Framingham participants eventually developed dementia associated with Alzheimer’s disease before the age of 85. This result was based on historical data rather than actually predicting future events, however—and there are other caveats to the new paper as well.
The AI focused on the oldest group of Framingham study participants, who mostly represent a non-Hispanic white population. This limits how much the results can be generalized to more diverse communities in the U.S. and the rest of the world, Au notes. It also remains unclear how the AI would perform in larger populations: the EClinicalMedicine study’s data set involved just 40 people who eventually developed dementia and 40 “controls” who did not, notes Jekaterina Novikova, director of machine learning at Winterlight Labs in Toronto. Novikova, who was not involved in the new study, also questions whether the performance of IBM’s AI would change when predicting the onset of Alzheimer’s at different points in time prior to diagnosis.
Still, she and Au praise the paper as a solid contribution to the field that might draw more attention and resources to AI detection of Alzheimer’s. “What I like personally about the [study] is that it’s one of the very few works that analyzes the big-scale, real-life data that was collected over a very long period of time,” Novikova says.
The new models might have been more accurate if it could have incorporated handwriting, Au suggests. This ability could have provided additional clues, such as evidence of tiny tremors, switching between print and cursive, and very tiny letters. “There are a lot of ... features that [the researchers] did not account for, which, combined with linguistic features, would have probably created an even more predictive model,” Au says. The IBM models also did not include data from spoken language. Using AI speech analysis to diagnose Alzheimer’s is a growing area of research, and other systems have focused on detecting changes in audio samples. These contain clues such as speech pauses, which are not found in writing.
Whether written or spoken, language samples offer a relatively noninvasive source of information for monitoring peoples’ cognitive health, compared with brain scans and other laboratory tests. Collecting such language data could be done cheaply and remotely—though doing so would still require strict informed consent and privacy safeguards for the individuals creating the samples, Royyuru says. This is especially true because some people may not want to even know how likely they are to develop Alzheimer’s disease—a condition that is currently irreversible.
Training models on spoken rather than written samples might prove more practical for achieving the broadest reach in the long run, given that writing requires literacy while speech does not. Novikova and her colleagues at Winterlight Labs have been focusing heavily on teaching AI to analyze the acoustic and linguistic characteristics in spoken words. And Au has been recording both speech and handwriting, using digital pens to capture the latter, for her research. IBM seems to be thinking along the same lines for its own future work.
“We are in the process of leveraging this technology to better understand diseases such as schizophrenia, [amyotrophic lateral sclerosis] and Parkinson's disease and are doing so in prospective studies [that] analyze spoken speech samples, given with consent from similar cognitive verbal tests,” says Guillermo Cecchi, a co-author of the new study and a principal researcher for computational psychiatry and neuroimaging at IBM.


scientificamerican--2020-10-22--U.S. Cities' Actions Fall Short of Lofty Climate Goals

Most major American cities that have signed on to the climate fight with pledges to cut greenhouse gas emissions are failing to meet their goals or have n't even started to track local progress , according to a survey by the Brookings Institution .
The report , `` Pledges and Progress , '' looked for climate policy and actions in the nation 's 100 most populous cities , finding that two-thirds have made commitments to address citywide emissions .
President Trump 's rejection of the Paris climate accord after he took office sparked a strong response at the local level @ @ @ @ @ @ @ and academics in taking the `` We Are Still In '' pledge to help meet targets for cutting emissions under the 2015 Paris Agreement .
The pledge now lists 3,800 signers .
`` At their best , the plans have exemplified the hope that 'bottom-up ' actions could add up to a powerful approach to climate mitigation , especially given rollbacks in federal policy under the Trump administration including the government 's withdrawal from the Paris Agreement , '' the report said .
But the Brookings analysis found that actions taken by cities @ @ @ @ @ @ @ to address climate change .
Among the 100 largest cities , only 45 set specific targets for cutting greenhouse gas emissions during the past decade and inventoried emissions levels within city boundaries as baselines for measuring progress .
Twenty-two more cities have made general pledges to address emissions .
But the Brookings analysis found they have n't set emissions targets or inventoried current emissions levels .
`` Half the cities are n't doing anything , '' said David Victor , co-chair of the Brookings Initiative on Energy and Climate .
Although there are @ @ @ @ @ @ @ , he said the split has obvious partisan roots .
Among the 45 cities fully engaged in the campaign , two-thirds are falling behind the emissions targets they set .
`` On average , all cities in the report need to cut their annual emissions by 64 % by 2050 in order to reach their respective goals , '' the authors wrote .
Mark Muro , senior fellow with the Metropolitan Policy Program at Brookings , said there are some encouraging local efforts , including in San Diego ; Richmond , Va. ; @ @ @ @ @ @ @ Several cities in California , including Oakland , San Francisco and Riverside , have the biggest climate gains by percentage emissions reductions .
Los Angeles is by far the pace setter in reducing carbon emissions within its boundaries .
That is in large part the result of municipal ownership of the Los Angeles Department of Water and Power , which has helped speed action on closing coal-fired power plants .
Greenhouse gas emissions in Los Angeles , assessed at 54 million metric tons in 1990 , had dropped to 29 million metric tons @ @ @ @ @ @ @ in the climate campaign were obvious even before the coronavirus pushed the nation 's economy into a dramatic downturn .
The Brookings results point to the challenges faced by cities whose climate commitments diverge from policies at the state level .
Another challenge for cities is the limits within which they operate .
City governments ca n't control everything that happens within their borders .
For example , when Pittsburgh inventoried greenhouse gas emissions in 2013 , it estimated an annual citywide total of 4.8 million metric tons .
Emissions from operations directly @ @ @ @ @ @ @ 115,069 metric tons .
The city government plans more reductions in part by buying refuse trucks that run on lower-emission compressed natural gas .
Its Parking Authority is teaming with Duquesne Light Co. to bring 16 new electric vehicle chargers to city parking lots .
These are marginal changes in a city and county with nearly 694,000 registered passenger vehicles .
Most of them run on gasoline engines that pump out carbon emissions .
So the city has to leverage policy where it can have greatest impact , Grant Ervin , Pittsburgh 's @ @ @ @ @ @ @ , told E & E News .
`` There 's a whole other side of our work that is really about developing a comprehensive land use strategy for the city of Pittsburgh , which is , effectively , how to use land at its most effective way to reduce carbon by reducing vehicle miles traveled . ''
Boston is among the major cities with climate commitments .
It joined the Metro Mayors Climate Mitigation Commitment in 2016 and pledged to achieve a carbon neutral economy by 2050 .
Last year , the Boston @ @ @ @ @ @ @ reaching the midcentury goal .
`` It requires an electricity grid that is powered by renewable sources of energy and a large-scale reduction in the use of oil and natural gas for transportation , space heating , and hot water , '' the report said .
The Boston blueprint said the city needs more public transportation that could replace personal cars .
And the remaining cars need to be battery-powered or powered by some other carbon-free source of energy .
That means that Boston 's success could hinge on efforts to build wind @ @ @ @ @ @ @ One major challenge for the city of Boston is its buildings , which are responsible for two-thirds of the city 's carbon emissions .
That includes the electricity they use and the oil and natural gas burned for heat and hot water .
Between 2,000 and 3,000 buildings annually will have to undergo a deep retrofit to install electric heating and hot water systems along with improvements in insulation for windows , walls and roofs .
Authors of the Boston report said achieving those goals requires a large , experienced workforce that does @ @ @ @ @ @ @ of project financing will be needed to provide the upfront capital necessary for deep retrofits and enable building owners to realize future energy cost savings , health improvements , and better comfort , '' the authors said .
Such solutions will have to come not only from federal incentives and energy policy , said Victor of Brookings , but also from an outpouring of experimentation and pioneering at the local and state level .
`` One of the great priorities [ is ] to make sure there is license for the heartland to @ @ @ @ @ @ @ .
Reprinted from Climatewire with permission from E & E News .
E & E provides daily coverage of essential energy and environmental news at www.eenews.net .

Most major American cities that have signed on to the climate fight with pledges to cut greenhouse gas emissions are failing to meet their goals or haven't even started to track local progress, according to a survey by the Brookings Institution.
The report, "Pledges and Progress," looked for climate policy and actions in the nation's 100 most populous cities, finding that two-thirds have made commitments to address citywide emissions.
President Trump's rejection of the Paris climate accord after he took office sparked a strong response at the local level. Mayors joined governors, business leaders and academics in taking the "We Are Still In" pledge to help meet targets for cutting emissions under the 2015 Paris Agreement. The pledge now lists 3,800 signers.
"At their best, the plans have exemplified the hope that 'bottom-up' actions could add up to a powerful approach to climate mitigation, especially given rollbacks in federal policy under the Trump administration including the government's withdrawal from the Paris Agreement," the report said.
But the Brookings analysis found that actions taken by cities aren't matching up with their pledges to address climate change.
Among the 100 largest cities, only 45 set specific targets for cutting greenhouse gas emissions during the past decade and inventoried emissions levels within city boundaries as baselines for measuring progress.
Twenty-two more cities have made general pledges to address emissions. But the Brookings analysis found they haven't set emissions targets or inventoried current emissions levels.
"Half the cities aren't doing anything," said David Victor, co-chair of the Brookings Initiative on Energy and Climate.
Although there are Republican mayors in the climate action ranks, he said the split has obvious partisan roots.
Among the 45 cities fully engaged in the campaign, two-thirds are falling behind the emissions targets they set. "On average, all cities in the report need to cut their annual emissions by 64% by 2050 in order to reach their respective goals," the authors wrote.
Mark Muro, senior fellow with the Metropolitan Policy Program at Brookings, said there are some encouraging local efforts, including in San Diego; Richmond, Va.; Greensboro, N.C.; and Cincinnati. Several cities in California, including Oakland, San Francisco and Riverside, have the biggest climate gains by percentage emissions reductions.
Los Angeles is by far the pace setter in reducing carbon emissions within its boundaries. That is in large part the result of municipal ownership of the Los Angeles Department of Water and Power, which has helped speed action on closing coal-fired power plants. Greenhouse gas emissions in Los Angeles, assessed at 54 million metric tons in 1990, had dropped to 29 million metric tons in 2013.
Coronavirus impact
But roadblocks facing mayors in the climate campaign were obvious even before the coronavirus pushed the nation's economy into a dramatic downturn.
The Brookings results point to the challenges faced by cities whose climate commitments diverge from policies at the state level. Another challenge for cities is the limits within which they operate. City governments can't control everything that happens within their borders.
For example, when Pittsburgh inventoried greenhouse gas emissions in 2013, it estimated an annual citywide total of 4.8 million metric tons. Emissions from operations directly under City Hall control came to just 115,069 metric tons. The city government plans more reductions in part by buying refuse trucks that run on lower-emission compressed natural gas. Its Parking Authority is teaming with Duquesne Light Co. to bring 16 new electric vehicle chargers to city parking lots.
These are marginal changes in a city and county with nearly 694,000 registered passenger vehicles. Most of them run on gasoline engines that pump out carbon emissions.
So the city has to leverage policy where it can have greatest impact, Grant Ervin, Pittsburgh's chief resilience officer and climate policy planner, told E&E News. "There's a whole other side of our work that is really about developing a comprehensive land use strategy for the city of Pittsburgh, which is, effectively, how to use land at its most effective way to reduce carbon by reducing vehicle miles traveled."
Boston is among the major cities with climate commitments. It joined the Metro Mayors Climate Mitigation Commitment in 2016 and pledged to achieve a carbon neutral economy by 2050.
Last year, the Boston Green Ribbon Commission issued a blueprint for reaching the midcentury goal. "It requires an electricity grid that is powered by renewable sources of energy and a large-scale reduction in the use of oil and natural gas for transportation, space heating, and hot water," the report said.
The Boston blueprint said the city needs more public transportation that could replace personal cars. And the remaining cars need to be battery-powered or powered by some other carbon-free source of energy. That means that Boston's success could hinge on efforts to build wind power installations off its Atlantic coast.
One major challenge for the city of Boston is its buildings, which are responsible for two-thirds of the city's carbon emissions. That includes the electricity they use and the oil and natural gas burned for heat and hot water.
Between 2,000 and 3,000 buildings annually will have to undergo a deep retrofit to install electric heating and hot water systems along with improvements in insulation for windows, walls and roofs. Authors of the Boston report said achieving those goals requires a large, experienced workforce that does not exist today.
"New forms of project financing will be needed to provide the upfront capital necessary for deep retrofits and enable building owners to realize future energy cost savings, health improvements, and better comfort," the authors said.
Such solutions will have to come not only from federal incentives and energy policy, said Victor of Brookings, but also from an outpouring of experimentation and pioneering at the local and state level.
"One of the great priorities [is] to make sure there is license for the heartland to innovate and act," he said.
Reprinted from Climatewire with permission from E&E News. E&E provides daily coverage of essential energy and environmental news at www.eenews.net.


scientificamerican--2020-10-22--Dinosaur Asteroid Hit Worst-Case Place

Dinosaur Asteroid Hit Worst-Case Place

We all know the story : 66 million years ago , a giant asteroid crashed into Earth , killing off three-quarters of all species , including most of the dinosaurs .
Researchers suspect that the impact caused the extinction by kicking up a cloud of dust and tiny droplets called aerosols that plunged the planet into something like a nuclear winter .
“ These components in the atmosphere drove global cooling and darkness that would have stopped photosynthesis from occurring , ultimately shutting down the food chain.
” But scientists have also found lots of soot in the geologic layers @ @ @ @ @ @ @ And the soot may have been part of the killing mechanism too—depending on where it came from .
Some of the soot probably came from wildfires that erupted around the planet following the impact .
But most of these particles would have lingered in the lower atmosphere for only a few weeks , and wouldn ’ t have had much of an effect on global climate .
But scientists hypothesize that soot may also have come from the very rocks that the asteroid pulverized when it struck .
If those rocks contained significant @ @ @ @ @ @ @ of marine organisms—it would have burned up on impact , sending soot shooting up into the stratosphere .
In that case , soot would have spread around the globe in a matter of hours and stayed there for years .
And it would have radically altered Earth ’ s climate .
So Lyons and her team set out to identify the source of the soot .
They looked at chemicals known as polycyclic aromatic hydrocarbons , or PAHs , which are another byproduct of combustion .
“ You can find PAHs in meat @ @ @ @ @ @ @ can find them from the exhaust of a car .
You can also find them in smoke and debris from the wildfires today out west.
” PAHs are made up of fused rings of carbon atoms—think of chicken wire .
To determine the origin of the soot , the researchers looked at the structure and chemistry of the PAHs buried along with it .
Specifically , the researchers looked for groups of atoms that stick off the rings like spikes .
PAHs generated from burning wood don ’ t have many spikes , @ @ @ @ @ @ @ would have been in the target rocks—have more .
Lyons and her team found that most of the PAHs deposited after the impact were spiky , which suggests that soot from the rocks hit by the asteroid played a major role in the mass extinction .
“ There was more dust and more sulfate aerosols than soot , but soot is a stronger blocker of sunlight than either of those two .
So a small amount of soot can drive large reductions in sunlight.
” The findings are in the Proceedings of the @ @ @ @ @ @ @ L. Lyons et al.
, Organic matter from the Chicxulub crater exacerbated the K–Pg impact winter ] The results suggest that the devastation of this very sooty asteroid impact may be due in part to a fluke of geography : the space rock smashed into the Gulf of Mexico , where the sediments were rich in organic matter .
They still are—the region produces large amounts of oil today .
“ Where it had occurred was likely one of the reasons that it led to a major mass extinction .
It was kind @ @ @ @ @ @ @ perfect asteroid impact , I guess you could call it.
” [ The above text is a transcript of this podcast . ]

Full Transcript
We all know the story: 66 million years ago, a giant asteroid crashed into Earth, killing off three quarters of all species, including most of the dinosaurs. Researchers suspect that the impact caused the extinction by kicking up a cloud of dust and tiny droplets called aerosols that plunged the planet into something like a nuclear winter.
“These components in the atmosphere drove global cooling and darkness that would have stopped photosynthesis from occurring, ultimately shutting down the food chain.”
Shelby Lyons, a recent Ph.D. graduate from Penn State University.
But scientists have also found lots of soot in the geologic layers deposited immediately after the asteroid impact. And the soot may have been part of the killing mechanism too—depending on where it came from.
Some of the soot probably came from wildfires that erupted around the planet following the impact. But most of these particles would have lingered in the lower atmosphere for only a few weeks and wouldn’t have had much of an effect on global climate.
But scientists hypothesize that soot may also have come from the very rocks that the asteroid pulverized when it struck. If those rocks contained significant amounts of organic matter—such as the remains of marine organisms—it would have burned up on impact, sending soot shooting up into the stratosphere. In that case, soot would have spread around the globe in a matter of hours and stayed there for years. And it would have radically altered Earth’s climate.
So Lyons and her team set out to identify the source of the soot. They looked at chemicals known as polycyclic aromatic hydrocarbons, or PAHs, which are another by-product of combustion.
“You can find PAHs in meat or veggies that you grill. You can find them from the exhaust of a car. You can also find them in smoke and debris from the wildfires today out west.”
PAHs are made up of fused rings of carbon atoms—think of chicken wire. To determine the origin of the soot, the researchers looked at the structure and chemistry of the PAHs buried along with it. Specifically, the researchers looked for groups of atoms that stick off the rings like spikes. PAHs generated from burning wood don’t have many spikes, but PAHs from burning fossil carbon—like what would have been in the target rocks—have more.
Lyons and her team found that most of the PAHs deposited after the impact were spiky, which suggests that soot from the rocks hit by the asteroid played a major role in the mass extinction.
“There was more dust and more sulfate aerosols than soot, but soot is a stronger blocker of sunlight than either of those two. So a small amount of soot can drive large reductions in sunlight.”
The findings are in the Proceedings of the National Academy of Sciences. [Shelby L. Lyons et al., Organic matter from the Chicxulub crater exacerbated the K–Pg impact winter]
The results suggest that the devastation of this very sooty asteroid impact may be due in part to a fluke of geography: the space rock smashed into the Gulf of Mexico, where the sediments were rich in organic matter. They still are: the region produces large amounts of oil today.
“Where it had occurred was likely one of the reasons that it led to a major mass extinction. It was kind of the perfect storm, or the perfect asteroid impact, I guess you could call it.”
—Julia Rosen
[The above text is a transcript of this podcast.]


scientificamerican--2020-10-21--Human Challenge Trials Will Deliberately Infect Dozens in the U.K.

Young , healthy people will be intentionally exposed to the virus responsible for COVID-19 in a first-of-its kind ‘ human challenge trial ’ , the UK government and a company that runs such studies announced on 20 October .
The experiment , set to begin in January in a London hospital if it receives final regulatory and ethical approval , aims to accelerate the development of vaccines that could end the pandemic .
Human challenge trials have a history of providing insight into diseases such as malaria and influenza .
The UK trial will try to identify a suitable dose @ @ @ @ @ @ @ used in future vaccine trials .
But the prospect of deliberately infecting people—even those at low risk of severe disease—with SARS-CoV-2 , a deadly pathogen that has few proven treatments , is uncharted medical and bioethical territory .
Proponents of COVID-19 challenge trials have argued that they can be run safely and ethically , and that their potential to quickly identify effective vaccines outweighs the low risks to participants .
But others have raised questions about the safety and value of these studies , pointing out that large-scale efficacy trials involving tens of @ @ @ @ @ @ @ results on several COVID-19 vaccines soon .
“ Deliberately infecting volunteers with a known human pathogen is never undertaken lightly .
However , such studies are enormously informative about a disease , ” said Peter Openshaw , an immunologist at Imperial College London and investigator on the study , in a press statement .
“ It is really vital that we move as fast as possible towards getting effective vaccines and other treatments for COVID-19 , and challenge studies have the potential to accelerate and de-risk the development of novel drugs and vaccines.
@ @ @ @ @ @ @ be led by a Dublin-based commercial clinical-research organization called Open Orphan and its subsidiary hVIVO , which runs challenge trials on respiratory pathogens .
It will take place in the high-level isolation unit of the Royal Free Hospital in north London , says Open Orphan executive chair Cathal Friel .
The UK government ’ s COVID-19 Vaccine Taskforce has agreed to pay the company up to £10 million ( US $ 13 million ) to conduct the trial , with the possibility of contracting Open Orphan to run several more to test various @ @ @ @ @ @ @ Regulatory Agency ( MHRA ) , which regulates clinical trials in the United Kingdom , and an ethical review committee , still need to approve the initial trial and its design , and that of future studies .
The initial trial will involve an estimated 30–50 participants , says Andrew Catchpole , a virologist and the chief scientific officer at Open Orphan who is leading the work .
It is open only to healthy adults aged 18–30 .
The precise design of the study has not been finalized .
But it is likely @ @ @ @ @ @ @ receive a very low dose of a SARS-CoV-2 ‘ challenge strain ’ derived from a currently circulating virus and grown under stringent conditions .
If none or few of the participants become infected , the researchers will seek permission from an independent safety monitoring board to expose participants to higher doses .
This process will be repeated until researchers identify a dose that infects most of those exposed , says Catchpole .
Once an appropriate dose is identified , Open Orphan could be asked to run a series of challenge trials testing several @ @ @ @ @ @ @ of these trials , including which vaccines will be included , has not been determined .
He envisions that some trial participants will receive a placebo injection instead of a vaccine , but he also says that head-to-head trials comparing two or more vaccines could be run .
Other vaccine studies that the company runs typically enrol 40–50 volunteers for each trial arm , he says .
Catchpole says that his team will take every precaution against participants in the initial trial developing severe disease .
Volunteers will be treated with an antiviral @ @ @ @ @ @ @ a nasal swab gives a positive result for SARS-CoV-2 genetic material .
In addition to age and health , participants will be screened for risk factors that have been associated with severe COVID-19 .
Selecting participants at the lowest risk is the most important safety step in running a challenge trial , says Matt Memoli , an infectious-disease physician and virologist at the US National Institute of Allergy and Infectious Diseases ( NIAID ) in Bethesda , Maryland .
“ Once you ’ ve given that virus to the person , anything ’ @ @ @ @ @ @ @ “ You can ’ t control it , you can only react to it.
” If Open Orphan moves on to vaccine trials , it will aim to recruit around 500 participants altogether , but Friel says the company will need to screen many times more people to identify suitable volunteers .
An ethical review board will determine how to compensate participants .
Open Orphan typically pays volunteers around £4,000 for their time , says Catchpole .
There is a concern that people will participate for the money without appreciating the risks , @ @ @ @ @ @ @ Rutgers University in New Brunswick , New Jersey , who has argued that COVID-19 challenge trials can be run safely and ethically .
But a well-designed online course , for instance , could ensure that participants understand the risks , he says .
Ensuring that participants understand the limitations of challenge trials will also be important , says Seema Shah , a bioethicist at Lurie Children ’ s Hospital and Northwestern University in Chicago , Illinois .
With phase III trials of numerous COVID-19 vaccines in the works , she thinks it unlikely @ @ @ @ @ @ @ of the first vaccines .
Instead , their payoff could lie in helping to test later-generation vaccines or laying the groundwork for fresh insights into the disease .
In this context , says Shah , “ It becomes a little bit harder to justify them , and we need to take a close look at risks.
” Meagan Deming , a vaccine scientist and virologist at the University of Maryland School of Medicine in Baltimore , sees challenge trials as more appropriate for studying basic aspects of SARS-CoV-2 infection—such as the potential for @ @ @ @ @ @ @ coronaviruses influences susceptibility to COVID-19—than for vetting vaccines .
Because such trials are likely to involve only young , healthy people , they might not reveal much about how vaccines could protect those most at risk of severe disease , such as older people and those with conditions such as diabetes , Deming says .
“ There ’ s a reason we don ’ t have a lot of vaccines approved by challenge models , because they don ’ t apply to everyone and you want a vaccine to protect almost everyone , @ @ @ @ @ @ @ might not offer clear evidence of whether vaccines work in older people , because of their low participation in those trials , says Peter Smith , an epidemiologist at the London School of Hygiene and Tropical Medicine who has been involved in challenge trials .
Researchers will probably need to determine vaccines ’ likely effectiveness in older people , on the basis of how their immune systems respond to COVID-19 vaccines before exposure to the virus .
And compared with field trials , challenge studies are better at identifying the types of immune @ @ @ @ @ @ @ likely to work or not , adds Memoli .
The United Kingdom isn ’ t the only country investigating COVID-19 challenge trials .
Belgium ’ s government has committed €20 million ( US $ 23.6 million ) for facilities to host challenge trials , potentially involving COVID-19 .
NIAID is funding the development of two SARS-CoV-2 challenge strains by a lab at Colorado State University in Fort Collins , and a team led by Memoli is also laying the groundwork for such trials .
In a statement , NIAID said it was awaiting @ @ @ @ @ @ @ decisions on COVID-19 challenge trials .
Proponents of the trials argue that the consequences of delaying them should be taken into account , alongside the risks of going forward .
For instance , Eyal and economists Pedro Rosa Dias and Ara Darzi at Imperial College London have calculated that speeding up the development of COVID-19 vaccines by one month would avert the loss of 720,000 years of life and prevent 40 million years in poverty , mostly in lower-income countries .
But Deming thinks that challenge trials should wait until their value is @ @ @ @ @ @ @ mitigated , for instance by deploying more potent therapies .
“ We don ’ t yet know enough about this disease to say for this person : you will not die , ” she says .
“ We ’ ve learned so much in the past nine months .
In a year , we will be able to do this safely.
” This article is reproduced with permission and was first published on October 20 2020 .

Young, healthy people will be intentionally exposed to the virus responsible for COVID-19 in a first-of-its kind ‘human challenge trial’, the UK government and a company that runs such studies announced on 20 October. The experiment, set to begin in January in a London hospital if it receives final regulatory and ethical approval, aims to accelerate the development of vaccines that could end the pandemic.
Human challenge trials have a history of providing insight into diseases such as malaria and influenza. The UK trial will try to identify a suitable dose of the virus SARS-CoV-2 that could be used in future vaccine trials. But the prospect of deliberately infecting people—even those at low risk of severe disease—with SARS-CoV-2, a deadly pathogen that has few proven treatments, is uncharted medical and bioethical territory.
Proponents of COVID-19 challenge trials have argued that they can be run safely and ethically, and that their potential to quickly identify effective vaccines outweighs the low risks to participants. But others have raised questions about the safety and value of these studies, pointing out that large-scale efficacy trials involving tens of thousands of people are expected to deliver results on several COVID-19 vaccines soon.
“Deliberately infecting volunteers with a known human pathogen is never undertaken lightly. However, such studies are enormously informative about a disease,” said Peter Openshaw, an immunologist at Imperial College London and investigator on the study, in a press statement. “It is really vital that we move as fast as possible towards getting effective vaccines and other treatments for COVID-19, and challenge studies have the potential to accelerate and de-risk the development of novel drugs and vaccines.”
Dose testing
The planned COVID-19 challenge study will be led by a Dublin-based commercial clinical-research organization called Open Orphan and its subsidiary hVIVO, which runs challenge trials on respiratory pathogens. It will take place in the high-level isolation unit of the Royal Free Hospital in north London, says Open Orphan executive chair Cathal Friel.
The UK government’s COVID-19 Vaccine Taskforce has agreed to pay the company up to £10 million (US$13 million) to conduct the trial, with the possibility of contracting Open Orphan to run several more to test various vaccines. The UK Medicines and Healthcare Regulatory Agency (MHRA), which regulates clinical trials in the United Kingdom, and an ethical review committee, still need to approve the initial trial and its design, and that of future studies.
The initial trial will involve an estimated 30–50 participants, says Andrew Catchpole, a virologist and the chief scientific officer at Open Orphan who is leading the work. It is open only to healthy adults aged 18–30.
The precise design of the study has not been finalized. But it is likely that a small number of participants will receive a very low dose of a SARS-CoV-2 ‘challenge strain’ derived from a currently circulating virus and grown under stringent conditions. If none or few of the participants become infected, the researchers will seek permission from an independent safety monitoring board to expose participants to higher doses. This process will be repeated until researchers identify a dose that infects most of those exposed, says Catchpole.
Once an appropriate dose is identified, Open Orphan could be asked to run a series of challenge trials testing several vaccines. Catchpole says that the design of these trials, including which vaccines will be included, has not been determined. He envisions that some trial participants will receive a placebo injection instead of a vaccine, but he also says that head-to-head trials comparing two or more vaccines could be run. Other vaccine studies that the company runs typically enrol 40–50 volunteers for each trial arm, he says.
Catchpole says that his team will take every precaution against participants in the initial trial developing severe disease. Volunteers will be treated with an antiviral drug, such as remdesivir, once a nasal swab gives a positive result for SARS-CoV-2 genetic material. In addition to age and health, participants will be screened for risk factors that have been associated with severe COVID-19.
Selecting participants at the lowest risk is the most important safety step in running a challenge trial, says Matt Memoli, an infectious-disease physician and virologist at the US National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland. “Once you’ve given that virus to the person, anything’s possible,” he says. “You can’t control it, you can only react to it.”
If Open Orphan moves on to vaccine trials, it will aim to recruit around 500 participants altogether, but Friel says the company will need to screen many times more people to identify suitable volunteers. An ethical review board will determine how to compensate participants. Open Orphan typically pays volunteers around £4,000 for their time, says Catchpole.
Ethical issues
There is a concern that people will participate for the money without appreciating the risks, says Nir Eyal, a bioethicist at Rutgers University in New Brunswick, New Jersey, who has argued that COVID-19 challenge trials can be run safely and ethically. But a well-designed online course, for instance, could ensure that participants understand the risks, he says.
Ensuring that participants understand the limitations of challenge trials will also be important, says Seema Shah, a bioethicist at Lurie Children’s Hospital and Northwestern University in Chicago, Illinois. With phase III trials of numerous COVID-19 vaccines in the works, she thinks it unlikely that challenge trials will speed the development of the first vaccines. Instead, their payoff could lie in helping to test later-generation vaccines or laying the groundwork for fresh insights into the disease. In this context, says Shah, “It becomes a little bit harder to justify them, and we need to take a close look at risks.”
Meagan Deming, a vaccine scientist and virologist at the University of Maryland School of Medicine in Baltimore, sees challenge trials as more appropriate for studying basic aspects of SARS-CoV-2 infection—such as the potential for reinfection or how previous exposure to cold-causing coronaviruses influences susceptibility to COVID-19—than for vetting vaccines. Because such trials are likely to involve only young, healthy people, they might not reveal much about how vaccines could protect those most at risk of severe disease, such as older people and those with conditions such as diabetes, Deming says. “There’s a reason we don’t have a lot of vaccines approved by challenge models, because they don’t apply to everyone and you want a vaccine to protect almost everyone,” she says.
Phase III trials might not offer clear evidence of whether vaccines work in older people, because of their low participation in those trials, says Peter Smith, an epidemiologist at the London School of Hygiene and Tropical Medicine who has been involved in challenge trials. Researchers will probably need to determine vaccines’ likely effectiveness in older people, on the basis of how their immune systems respond to COVID-19 vaccines before exposure to the virus. And compared with field trials, challenge studies are better at identifying the types of immune response that predict whether a vaccine is likely to work or not, adds Memoli.
Other trials
The United Kingdom isn’t the only country investigating COVID-19 challenge trials. Belgium’s government has committed €20 million (US$23.6 million) for facilities to host challenge trials, potentially involving COVID-19. NIAID is funding the development of two SARS-CoV-2 challenge strains by a lab at Colorado State University in Fort Collins, and a team led by Memoli is also laying the groundwork for such trials. In a statement, NIAID said it was awaiting data from phase III studies before making decisions on COVID-19 challenge trials.
Proponents of the trials argue that the consequences of delaying them should be taken into account, alongside the risks of going forward. For instance, Eyal and economists Pedro Rosa Dias and Ara Darzi at Imperial College London have calculated that speeding up the development of COVID-19 vaccines by one month would avert the loss of 720,000 years of life and prevent 40 million years in poverty, mostly in lower-income countries.
But Deming thinks that challenge trials should wait until their value is clearer and the risks can be better mitigated, for instance by deploying more potent therapies. “We don’t yet know enough about this disease to say for this person: you will not die,” she says. “We’ve learned so much in the past nine months. In a year, we will be able to do this safely.”
This article is reproduced with permission and was first published on October 20 2020.


scientificamerican--2020-10-21--Teaching Antiracism to the Next Generation of Doctors

A psychotic Black woman admitted to a psychiatric emergency room is discharged “ to the streets , ” despite being pregnant and disorganized .
Several white health care providers , noting her history of methamphetamine use , joke “ she ’ s always like this ” and claim she is “ at baseline , ” suggesting she is inherently inferior and unworthy of treatment .
They make no effort to contact her family , provide prenatal care or admit her to the hospital , carelessly disregarding the potential harm to her and her unborn child .
When two Black parents @ @ @ @ @ @ @ their child , the pediatricians consider reporting them to child protective services for neglect .
The pediatricians themselves neglect to fully explain the complex medical details to the terrified parents .
Only when a consulting psychiatric service recognizes the parents ’ legitimate fears and the absence of appropriate education do the pediatricians refocus on improving medical care , rather than reporting .
In neither case is the providers ’ medical racism challenged , sanctioned or remediated .
As a physician-educator teaching about racism , my primary goal is ensuring the next generation of @ @ @ @ @ @ @ discrimination , which is common within the American health care system .
Unfortunately , existing medical education pedagogies , such as the social determinants of health and cultural competency , do not challenge the racism perpetuated by a predominantly white health care workforce charged with caring for a racially diverse public they do not represent .
They are increasingly out of sync with the demands for anti-racism following the murders of Ahmaud Arbery , George Floyd and Breonna Taylor and the coronavirus ’ s disproportionate killing of Black lives .
Instead , I @ @ @ @ @ @ @ Kendi ’ s scholarship that helps students identify racism ’ s far-reaching grasp on health care so they can challenge it and honor their oath to first do no harm .
Rather than master a competency , I invite them to begin a lifelong journey intended to excavate the racism , anti-Blackness and white supremacy shaping their profession , their country , and themselves .
Learning the legacy of slavery in American medicine is key to this process .
To echo a recent New England Journal of Medicine editorial , `` Slavery has @ @ @ @ @ @ @ , and brutality that runs from 1619 to the present , and that legacy infects medicine as it does all social institutions.
” Ta-Nehisi Coates ’ ethical , legal and economic justification for reparations and Carol Anderson ’ s discussion of the white rage pushing back on Black economic and civic advancement are not typical medical education content .
But because they elucidate slavery ’ s long arc in American history and render parallel arcs in American medicine more visible and less refutable , they are requisite teaching .
My students learn that @ @ @ @ @ @ @ pregnant Black woman is “ just like that ” or “ at baseline ” and discharge her to the streets with no plan for shelter , they are advancing the same narrative of Black mental inferiority and physical imperviousness to harm that 19th-century doctors used to justify slavery .
When they report Black families to family services as a form of coercion , in lieu of offering the standard of care by providing education , they are pathologizing their suffering and disregarding their historical mistreatment by the health care system .
Failing to @ @ @ @ @ @ @ is not only negligent .
It upholds the assault on Black women ’ s reproductive health foundational to slavery , maintained through forced-sterilization campaigns lasting into the 1970s , and enduring in their higher risk for maternal mortality today .
Recognizing the legacy of slavery in American medicine enables students to discern contemporary racism .
It simultaneously elucidates why , as a Lancet editorial recently stated , “ Racism is a public health emergency of global concern .
It is the root cause of continued disparities in death and disease between Black and @ @ @ @ @ @ @ challenging racism ’ s deleterious effects requires first identifying its many forms .
Camara Phyllis Jones ’ classic multilevel framework emphasizes how racism is internalized , operates interpersonally through implicit bias and micro-aggressions , and functions on more macro levels through institutions , policies and ideologies .
Racism ’ s multiple levels can powerfully collide , resulting in dangerous clinical “ care.
” Using this model , students learn why microaggressions , such as ignoring a patient ’ s subjective complaint of shortness of breath , are anything but “ micro ” and @ @ @ @ @ @ @ when they intersect with the health care system ’ s inadequacies .
All this must be understood against a background of white supremacy that has lynched and massacred countless Black Americans .
Accordingly , white doctors ’ silence when white patients hurl racial slurs at their Black colleagues is equally damaging to health .
They also learn how racist policies and ideologies operating outside of health care influence clinical interactions .
The War on Drugs , fabricated in the 1970s to push back on Black advancement from the Civil Rights Movement , was @ @ @ @ @ @ @ and violence perpetuated , in part , by American psychiatrists .
Doctors , no less immune to these racist ideologies , are equally prone to the disproportionate punishment and policing of Black lives well-documented in school and law enforcement settings .
Common clinical practices , like administering forced intramuscular medication , discharging someone who should be hospitalized , or reporting a family to family services , become coercive when the racism driving them proceeds unchecked .
The ostensible scientific neutrality of clinical decision-making can obfuscate the racism that leads doctors to misdiagnose , @ @ @ @ @ @ @ pathologize emotional responses .
However , recognizing slavery ’ s legacy and racism ’ s multiple levels renders such bias more visible , preparing students to engage in anti-racist clinical care .
I ask them to disavow the prevailing medical culture that encourages perfection and , instead , admit to being racist in order to become anti-racist .
Challenging racism ’ s multiple levels and historical arcs is an established anti-racist approach but not a common one in medical education .
My best hope is that in the absence of broader accountability from @ @ @ @ @ @ @ of education will not only prevent students from participating in the clinical racism I described earlier .
It will provide shared language for them to collectively speak out and heighten their conscience and consciousness enough so they first do no harm .
Unfortunately , the next generation of doctors is training within a health care system steeped in racism .
They are demanding anti-racist medical education from majority-white faculty unequipped to train them .
The white fragility of academic medicine , which is dominated by white male leadership , may impede meaningful anti-racist @ @ @ @ @ @ @ few effective outlets for reporting discrimination and remediating it .
As students become more familiar with anti-racist pedagogy , they are bound to report racism at academic medical centers more frequently .
The process is likely to be contentious .
Following an incident during a lecture on gender-based violence at the University of Washington School of Medicine , for example , a coalition of Black students recently called for the removal of three professors for “ anti-Black , racist ” behavior .
If my recent discussions are any indication , the next generation @ @ @ @ @ @ @ identify the racism that stripped George Floyd of his life and to leverage the weight of their authority to protect rather than harm their patients .
They are simultaneously seeking structural reforms to ensure sustained equality .
The question is : Are the academic medical centers where they train prepared to teach them to do so ?

Editor’s Note (12/21/21): This article is being showcased in a special collection about equity in health care that was made possible by the support of Takeda Pharmaceuticals. The article was published independently and without sponsorship.
A psychotic Black woman admitted to a psychiatric emergency room is discharged “to the streets,” despite being pregnant and disorganized. Several white health care providers, noting her history of methamphetamine use, joke “she’s always like this” and claim she is “at baseline,” suggesting she is inherently inferior and unworthy of treatment. They make no effort to contact her family, provide prenatal care or admit her to the hospital, carelessly disregarding the potential harm to her and her unborn child.
When two Black parents refuse a potentially life-saving organ transplant for their child, the pediatricians consider reporting them to child protective services for neglect. The pediatricians themselves neglect to fully explain the complex medical details to the terrified parents. Only when a consulting psychiatric service recognizes the parents’ legitimate fears and the absence of appropriate education do the pediatricians refocus on improving medical care, rather than reporting.
In neither case is the providers’ medical racism challenged, sanctioned or remediated.
As a physician-educator teaching about racism, my primary goal is ensuring the next generation of doctors never engages in this kind of discrimination, which is common within the American health care system. Unfortunately, existing medical education pedagogies, such as the social determinants of health and cultural competency, do not challenge the racism perpetuated by a predominantly white health care workforce charged with caring for a racially diverse public they do not represent. They are increasingly out of sync with the demands for antiracism following the murders of Ahmaud Arbery, George Floyd and Breonna Taylor and the coronavirus’s disproportionate killing of Black lives.
Instead, I teach an antiracist approach informed by Ibram Kendi’s scholarship that helps students identify racism’s far-reaching grasp on health care so they can challenge it and honor their oath to first do no harm. Rather than master a competency, I invite them to begin a lifelong journey intended to excavate the racism, anti-Blackness and white supremacy shaping their profession, their country, and themselves.
Learning the legacy of slavery in American medicine is key to this process. To echo a recent New England Journal of Medicine editorial, "Slavery has produced a legacy of racism, injustice, and brutality that runs from 1619 to the present, and that legacy infects medicine as it does all social institutions.” Ta-Nehisi Coates’ ethical, legal and economic justification for reparations and Carol Anderson’s discussion of the white rage pushing back on Black economic and civic advancement are not typical medical education content. But because they elucidate slavery’s long arc in American history and render parallel arcs in American medicine more visible and less refutable, they are requisite teaching.
My students learn that when health care providers claim a psychotic pregnant Black woman is “just like that” or “at baseline” and discharge her to the streets with no plan for shelter, they are advancing the same narrative of Black mental inferiority and physical imperviousness to harm that 19th-century doctors used to justify slavery. When they report Black families to family services as a form of coercion, in lieu of offering the standard of care by providing education, they are pathologizing their suffering and disregarding their historical mistreatment by the health care system. Failing to hospitalize a medically acute Black pregnant woman is not only negligent. It upholds the assault on Black women’s reproductive health foundational to slavery, maintained through forced-sterilization campaigns lasting into the 1970s, and enduring in their higher risk for maternal mortality today.
Recognizing the legacy of slavery in American medicine enables students to discern contemporary racism. It simultaneously elucidates why, as a Lancet editorial recently stated, “Racism is a public health emergency of global concern. It is the root cause of continued disparities in death and disease between Black and white people in the USA.”
But challenging racism’s deleterious effects requires first identifying its many forms. Camara Phyllis Jones’ classic multilevel framework emphasizes how racism is internalized, operates interpersonally through implicit bias and micro-aggressions, and functions on more macro levels through institutions, policies and ideologies. Racism’s multiple levels can powerfully collide, resulting in dangerous clinical “care.” Using this model, students learn why microaggressions, such as ignoring a patient’s subjective complaint of shortness of breath, are anything but “micro” and can, in fact, be deadly when they intersect with the health care system’s inadequacies. All this must be understood against a background of white supremacy that has lynched and massacred countless Black Americans. Accordingly, white doctors’ silence when white patients hurl racial slurs at their Black colleagues is equally damaging to health.
They also learn how racist policies and ideologies operating outside of health care influence clinical interactions. The War on Drugs, fabricated in the 1970s to push back on Black advancement from the Civil Rights Movement, was reinforced by an ideology of Black criminality and violence perpetuated, in part, by American psychiatrists. Doctors, no less immune to these racist ideologies, are equally prone to the disproportionate punishment and policing of Black lives well-documented in school and law enforcement settings. Common clinical practices, like administering forced intramuscular medication, discharging someone who should be hospitalized, or reporting a family to family services, become coercive when the racism driving them proceeds unchecked.
The ostensible scientific neutrality of clinical decision-making can obfuscate the racism that leads doctors to misdiagnose, deny treatment, silence subjective complaints and pathologize emotional responses. However, recognizing slavery’s legacy and racism’s multiple levels renders such bias more visible, preparing students to engage in antiracist clinical care. I ask them to disavow the prevailing medical culture that encourages perfection and, instead, admit to being racist in order to become antiracist.
Challenging racism’s multiple levels and historical arcs is an established antiracist approach but not a common one in medical education. My best hope is that in the absence of broader accountability from the health care system, this kind of education will not only prevent students from participating in the clinical racism I described earlier. It will provide shared language for them to collectively speak out and heighten their conscience and consciousness enough so they first do no harm.
Unfortunately, the next generation of doctors is training within a health care system steeped in racism. They are demanding antiracist medical education from majority-white faculty unequipped to train them. The white fragility of academic medicine, which is dominated by white male leadership, may impede meaningful antiracist educational reform. Furthermore, there are few effective outlets for reporting discrimination and remediating it. As students become more familiar with antiracist pedagogy, they are bound to report racism at academic medical centers more frequently. The process is likely to be contentious. Following an incident during a lecture on gender-based violence at the University of Washington School of Medicine, for example, a coalition of Black students recently called for the removal of three professors for “anti-Black, racist” behavior.
If my recent discussions are any indication, the next generation of doctors is primed to name and identify the racism that stripped George Floyd of his life and to leverage the weight of their authority to protect rather than harm their patients. They are simultaneously seeking structural reforms to ensure sustained equality. The question is: Are the academic medical centers where they train prepared to teach them to do so?


scientificamerican--2020-10-23--Beehives on a Cliff Wall Are Protected from Predators and Pesticides

Bees do not usually buzz around wooden hives 4,000 feet above sea level , but keepers have placed about 700 @ @ @ @ @ on the side of a mountain in Shennongjia National Nature Reserve in China ’ s @ @ @ @ @ populations have been shrinking .
On the high cliff wall , however , they are @ @ @ @ @ hazards , such as pesticides .
The hive boxes also attract wild bees to come @ @ @ @ @ scale the cliff using rope ladders to check on the hives and collect the honey @ @ @ @ @ a new category of articles featuring photographs and videos from all the disciplines of science @ @ @ @ @ below to see the full collection .

Bees do not usually buzz around wooden hives 4,000 feet above sea level, but keepers have placed about 700 bee colonies at that height on the side of a mountain in Shennongjia National Nature Reserve in China’s Hubei Province. Asian honeybee populations have been shrinking. On the high cliff wall, however, they are safe from predators and other hazards, such as pesticides. The hive boxes also attract wild bees to come and settle. The keepers scale the cliff using rope ladders to check on the hives and collect the honey.
Science in Images is a new category of articles featuring photographs and videos from all the disciplines of science. Click on the button below to see the full collection.
Science in Images