“Extreme temperature events are becoming more frequent, longer and more intense, and their adverse health effects have drawn growing concern. Another environmental issue worldwide is the presence of fine particulate matter in the air, which may interact synergistically with extreme temperatures to adversely affect cardiovascular health,” said senior author Yuewei Liu, M.D., Ph.D., an associate professor of epidemiology in the School of Public Health at Sun Yat-sen University in Guangzhou, China. “However, it remains unknown if and how co-exposure to extreme temperatures and fine particulate pollution might interact to trigger a greater risk of death from heart attack, which is an acute response potentially brought on by an acute scenario and a great public health challenge due to its substantial disease burden worldwide.”

To examine the impact of extreme temperatures with and without high levels of fine particulate pollution, the researchers analyzed 202,678 heart attack deaths between 2015-2020 that occurred in Jiangsu province, a region with four distinct seasons and a wide range of temperatures and fine particulate pollution levels. The deaths were among older adults with an average age of 77.6 years; 52% were older than age 80; and 52% were male. Particulate exposure on the day of each death and one day before death were included in the analysis.

Extreme temperatures were gauged according to the daily heat index (also referred to as apparent temperature) for an area, which captures the combined effect of both heat and humidity. Both the length and extremeness of heat waves and cold snaps were evaluated. Heart attack deaths, or case days, during these periods were compared with control days on the same day of the week in the same month — meaning that if a death occurred on a Wednesday, all other Wednesdays in the same month would be considered control days. Particulate levels were considered high on any day with an average level of fine particulate matter above 37.5 micrograms per cubic meter.

“Our findings provide evidence that reducing exposure to both extreme temperatures and fine particulate pollution may be useful to prevent premature deaths from heart attack, especially for women and older adults,” Liu said.

Compared with control days, the risk of a fatal heart attack was observed at the following levels:

• 18% higher during 2-day heat waves with heat indexes at or above the 90^th percentile (ranging from 82.6 to 97.9 degrees Fahrenheit), increasing with temperature and duration, and was 74% higher during 4-day heat waves with heat indexes at or above the 97.5^th percentile (ranging from 94.8 to 109.4 degrees Fahrenheit). For context, 6,417 (3.2%) of the 202,678 observed deaths from heart attack happened during heat waves with heat indexes at or above the 95^th percentile (ranging from 91.2 to 104.7 degrees Fahrenheit) for three or more days.
• 4% higher during 2-day cold snaps with temperatures at or below the 10^th percentile (ranging from 33.3 to 40.5 degrees Fahrenheit), increasing with lower temperatures and duration, and was 12% higher during 3-day cold snaps with temperatures at or below the 2.5^th percentile (ranging from 27.0 to 37.2 degrees Fahrenheit). For context, 6,331 (3.1%) of the 202,678 observed deaths from heart attack happened during cold spells with temperatures at or below the 5^th percentile (ranging from 30.0 to 38.5 degrees Fahrenheit) for 3 or more days.
• Twice as high during 4-day heat waves that had fine particulate pollution above 37.5 micrograms per cubic meter. Days with high levels of fine particulate pollution during cold snaps did not have an equivalent increase in the risk of heart attack death.
• Generally higher among women than men during heat waves.
• Higher among people ages 80 and older than in younger adults during heat waves, cold snaps or days with high levels of fine particulate pollution.
• The mean age of all individuals who died from a heart attack in Jiangsu from 2015-2020, including during non-extreme temperature events, was 77.6 years old; 52.1% of these individuals were over 80 years old.

The researchers estimated that up to 2.8% of heart attack deaths may be attributed to the combination of extreme temperatures and high levels of fine particulate pollution (> 37.5 micrograms per cubic meter), according to WHO targets.

“Strategies for individuals to avoid negative health effects from extreme temperatures include following weather forecasts, staying inside when temperatures are extreme, using fans and air conditioners during hot weather, dressing appropriately for the weather, proper hydration and installing window blinds to reduce indoor temperatures,” said Liu. “Using an air purifier in the house, wearing a mask outdoors, staying clear of busy highways when walking and choosing less-strenuous outdoor activities may also help to reduce exposure to air pollution on days with high levels of fine particulate pollution. To improve public health, it is important to take fine particulate pollution into consideration when providing extreme temperature warnings to the public.”

In a 2020 scientific statement and a 2020 policy statement, the American Heart Association details the latest science about air pollution exposure and the individual, industrial and policy measures to reduce the negative impact of poor air quality on cardiovascular health. Reducing exposure to air pollution and reversing the negative impact of poor air quality on cardiovascular health, including heart disease and stroke, is essential to reducing health inequities in Black and Hispanic communities, those that have been historically marginalized and under-resourced, and communities that have the highest levels of exposure to air pollution.

The investigators recommended additional research about the possible interactive effects of extreme weather events and fine particulate pollution on heart attack deaths in areas with different temperature and pollution ranges to confirm their findings. The study did not include adjustments for any adaptive behaviors taken by individuals, such as using air conditioning and staying indoors, when temperatures are extreme or pollution levels are high, which could cause misclassification of individuals’ exposure to weather and alter their risk patterns. These results also may not be generalizable to other regions in China or other countries due to potential variations of adaption capacity and temperature distribution.

Background:

• Fine particulates are less than 2.5 microns in size and may be inhaled deep into the lungs, where they can irritate the lungs and blood vessels around the heart. Most are associated with fuel combustion, such as particles from car exhaust, factory emissions or wildfires.
• Previous research has confirmed that exposure to particulate matter including fine particulates is linked to heart disease, stroke and other health issues.
• For context, the World Health Organization’s target for average annual exposure to fine particulate pollution level is no more than 5 micrograms per cubic meter and no more than 15 micrograms per cubic meter for more than 3-4 days per year.
• In this study, heat waves were defined as periods at or above the 90^th, 92.5^th, 95^th and 97.5^th percentiles of daily heat indexes (ranging from 82.6 to 109.4 degrees Fahrenheit across Jiangsu province, China) for at least 2, 3 or 4 consecutive days.
• Cold spells were defined as periods at or below the 10^th, 7.5^th, 5^th, 2.5^th percentiles of daily heat indexes (ranging from 27 to 40.5 degrees Fahrenheit) for at least 2, 3 or 4 consecutive days.

According to the law of conservation of energy, energy is never created or destroyed but only changes form from one to another depending on the interaction between the entities involved. All energy eventually ends up as heat. For us that can be a useful thing, for example, when we want to heat our homes in winter; or detrimental, when we want to cool something down, or get the most out of a battery-driven application. In any case, the better we can manage the thermal behavior of a device, the better we can engineer around this inevitable effect and improve the efficiency of the device in question. However, this is easier said than done, as knowing how heat flows inside some complex, miniature or hazardous device is something ranging from the difficult to the impossible, depending on the application.

Inspired by this problem, Project Associate Professor Tomoya Higo and Professor Satoru Nakatsuji from the Department of Physics at the University of Tokyo, and their team, which included a corporate partnership, set out to find a solution. “The amount of heat conducted through a material is known as its heat flux. Finding new ways to measure this could not only help improve device efficiency, but also safety, as batteries with poor thermal management can be unsafe, and even health, as various health or lifestyle issues can relate to body heat,” said Higo. “But finding a sensor technology to measure heat flux, while also satisfying a number of other conditions, such as robustness, cost efficiency, ease of manufacture and so on, is not easy. Typical thermal diode devices are relatively large and only give a value for temperature in a specific area, rather than an image, of the heat flux across an entire surface.”

The team explored the way a heat flux sensor consisting of certain special magnetic materials and electrodes behaves when there are complex patterns of heat flow. The magnetic material based on iron and gallium exhibits a phenomenon known as the anomalous Nernst effect (ANE), which is where heat energy is unusually converted to an electrical signal. This is not the only magnetic effect that can turn heat into power, though. There is also the Seebeck effect, which can actually create more electrical power, but it requires a large bulk of material, and the materials are brittle so hard to work with. ANE, on the other hand, allowed the team to engineer their device on an incredibly thin and malleable sheet of plastic.

“By finding the right magnetic and electrode materials and then applying them in a special repeating pattern, we created microscopic electronic circuits that are flexible, robust, cheap and easy to produce, and most of all are very good at outputting heat flux data in real time,” said Higo. “Our method involves rolling a thin sheet of clear, strong and lightweight PET plastic as a base layer, with magnetic and electrode materials sputtered onto it in thin and consistent layers. We then etch our desired patterns into the resultant film, similar to how electronic circuits are made.”

The team designed the circuits in a particular kind of way to boost ANE whilst also suppressing the Seebeck effect, as this actually interferes with the data-gathering potential of ANE. Previous attempts to do this were unsuccessful in any way that could be easily scaled up and potentially commercialized, making this sensor the first of its kind.

“I envisage seeing downstream applications such as power generation or data centers, where heat impedes efficiency. But as the world becomes more automated, we might see these kinds of sensors in automated manufacturing environments where they could improve our ability to predict machine failures, certain safety issues, and more,” said Nakatsuji. “With further developments, we might even see internal medical applications to help doctors produce internal heat maps of specific areas of the body, or organs, to aid in imaging and diagnosis.”

New measurements by NASA’s James Webb Space Telescope’s MIRI (Mid-Infrared Instrument) have detected water vapor in the system’s inner disk, at distances of less than 100 million miles (160 million kilometers) from the star — the region where rocky, terrestrial planets may be forming. (The Earth orbits 93 million miles from our Sun.) This is the first detection of water in the terrestrial region of a disk already known to host two or more protoplanets.

“We’ve seen water in other disks, but not so close in and in a system where planets are currently assembling. We couldn’t make this type of measurement before Webb,” said lead author Giulia Perotti of the Max Planck Institute for Astronomy (MPIA) in Heidelberg, Germany.

“This discovery is extremely exciting, as it probes the region where rocky planets similar to Earth typically form,” added MPIA director Thomas Henning, a co-author on the paper. Henning is co-principal investigator of Webb’s MIRI (Mid-Infrared Instrument), which made the detection, and the principal investigator of the MINDS (MIRI Mid-Infrared Disk Survey) program that took the data.

A Steamy Environment for Forming Planets

PDS 70 is a K-type star, cooler than our Sun, and is estimated to be 5.4 million years old. This is relatively old in terms of stars with planet-forming disks, which made the discovery of water vapor surprising.

Over time, the gas and dust content of planet-forming disks declines. Either the central star’s radiation and winds blow out such material, or the dust grows into larger objects that eventually form planets. As previous studies failed to detect water in the central regions of similarly aged disks, astronomers suspected it might not survive the harsh stellar radiation, leading to a dry environment for the formation of any rocky planets.

Astronomers haven’t yet detected any planets forming within the inner disk of PDS 70. However, they do see the raw materials for building rocky worlds in the form of silicates. The detection of water vapor implies that if rocky planets are forming there, they will have water available to them from the beginning.

“We find a relatively high amount of small dust grains. Combined with our detection of water vapor, the inner disk is a very exciting place,” said co-author Rens Waters of Radboud University in The Netherlands.

What is the Water’s Origin?

The discovery raises the question of where the water came from. The MINDS team considered two different scenarios to explain their finding.

One possibility is that water molecules are forming in place, where we detect them, as hydrogen and oxygen atoms combine. A second possibility is that ice-coated dust particles are being transported from the cool outer disk to the hot inner disk, where the water ice sublimates and turns into vapor. Such a transport system would be surprising, since the dust would have to cross the large gap carved out by the two giant planets.

Another question raised by the discovery is how water could survive so close to the star, when the star’s ultraviolet light should break apart any water molecules. Most likely, surrounding material such as dust and other water molecules serves as a protective shield. As a result, the water detected in the inner disk of PDS 70 could survive destruction.

Ultimately, the team will use two more of Webb’s instruments, NIRCam (Near-Infrared Camera) and NIRSpec (Near-Infrared Spectrograph) to study the PDS 70 system in an effort to glean an even greater understanding.

These observations were taken as part of Guaranteed Time Observation program 1282. This finding has been published in the journal Nature.

The new study, published July 21, 2023 in Science Advances, reveals how changes to the 3D structures of integrase, an HIV protein, can lead to Dolutegravir resistance and how other compounds may be able to overcome this resistance.

“With HIV, one must think two steps ahead of the virus,” says Salk Associate Professor Dmitry Lyumkis, co-senior author and the Hearst Foundation Developmental Chair. “We’ve now determined how the virus could continue evolving against drugs like Dolutegravir, which is important to consider for the development of future therapeutics.”

HIV infection depends on the ability of the virus to paste its own genetic material into the genomes of human cells, essentially hijacking the cells to become virus-producing factories. Dolutegravir and related drugs work by blocking integrase, a protein critical to the ability of the virus to integrate its own DNA into the host genome. Without functioning integrase, HIV can’t effectively infect human cells. However, HIV is a rapidly mutating virus, and an increasing number of HIV strains are resistant to Dolutegravir.

In the past, Lyumkis’ lab discovered the 3D structure of the integrase protein while attached to DNA as well as exactly how drugs like Dolutegravir bind to and block integrase. But researchers weren’t sure how the integrase structure changed when the virus stopped responding to Dolutegravir.

In the new study, Lyumkis and collaborators from the National Institutes of Health created versions of the integrase protein with mutations known to make HIV resistant to Dolutegravir. Then they determined the structure of each mutant integrase, revealing why Dolutegravir could no longer bind to and block each version of the protein. The scientists also evaluated the “fitness” of the virus (its capacity to produce infectious descendants) and the activity of the enzyme to better understand what leads to drug resistance in patients.

“We were quite surprised by the magnitude of resistance that these integrase variants had,” says Lyumkis. “The ability of Dolutegravir to function was completely compromised.”

The researchers also tested the efficacy of an experimental HIV drug, 4d, to block the function of Dolutegravir-resistant integrase proteins. 4d was developed by Lyumkis’ collaborators at the NIH as a next-generation integrase-targeting drug and is currently in pre-clinical animal trials. In all the variants, they discovered that 4d still potently blocked the ability of HIV to integrate its genes into human cells. This suggests that 4d or variants of this compound may be effectively used to treat the virus in patients who have developed resistance to Dolutegravir.

The structural data on how 4d binds to the Dolutegravir-resistant integrase proteins also hinted at how new drugs could overcome drug resistance.

“4d is really just an example of how to combat drug resistance, but it provides us with some basic principles that we can learn from to design other therapeutics,” says co-senior author Robert Craigie of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health. “The way a section of the 4d molecule stacks like a flat sheet on top of a section of the integrase protein-DNA assembly could be replicated in other compounds.”

Next, the scientists will study how integrase variants evolve — including those not yet seen in patients but possible in the future — and how they impact response to the best clinically used drugs as well as the ability of HIV to infect humans.

Other authors include Dario Oliveira Passos, Zelin Shan, Avik Biswas and Timothy S. Strutzenberg of Salk; Min Li, Zhaoyang Li, Steven J. Smith, Xue Zhi Zhao, Terrence R. Burke, Jr. and Stephen H. Hughes of the National Institutes of Health; Qinfang Sun, Indrani Choudhuri, Allan Haldane, and Ronald M. Levy of Temple University; Nanjie Deng of Pace University; and Lorenzo Briganti and Mamuka Kvaratskhelia of University of Colorado Anschutz Medical Campus.

“The first two years is a really critical period where a lot of development is going on, and sleep is important for health. We wanted to look at the association of mother and infant sleep and whether it changes over time,” said Tianying Cai, now a postdoctoral researcher at Northwestern University. She worked on the research as a doctoral student in the Department of Human Development and Family Studies (HDFS), part of the College of Agricultural, Consumer and Environmental Sciences (ACES) at the U. of I.

“We identified two distinct groups, a low maternal sleep group where the mothers get 5 to 6 hours of sleep per night, and an average maternal sleep group, which meets the national recommended sleep guidelines with 7 to 8 hours per night. Children in the low maternal sleep group also slept less, although the difference wasn’t as large as for the mothers,” Cai stated.

The research team followed parents of 464 infants in the first two years of life. Mothers completed surveys about bedtime routines, their child’s sleep duration, nighttime waking, and sleep problems at 3, 12, 18, and 24 months of age.

The families were part of STRONG Kids 2, a program at the U. of I. that promotes nutrition and healthy habits in families with young children. STRONG Kids 2 co-directors Barbara Fiese, professor emerita of HDFS, and Sharon Donovan, professor of food science and human nutrition, also contributed to the study.

Mothers who fit the low maternal sleep profile got an average of 5.74 hours of sleep per night at 3 months and 5.9 hours at 12 to 24 months, while their children got 9.6 and 10.52 hours, respectively. In the average sleep profile, mothers got 7.31 hours at 3 months and 7.28 hours at 12 to 24 months, while child sleep averaged 9.99 hours at 3 months and 11 hours at 12 to 24 months.

The research team also identified factors that influence the amount of sleep a mother gets. Not surprisingly, one of the strongest predictors is infant-signaled nighttime waking, which means the infant is more likely to alert the parent at night. This could be either because these infants woke more frequently, or because the mothers were more likely to wake up when infants stirred, Cai noted.

Mothers who had longer employment hours were more likely to be in the low sleep group at 3 months, although that was no longer a factor by 12 months. Furthermore, those who breastfed their infant at 12 months were more likely to be in the average sleep group.

Over time, many families transitioned from the low to the average sleep group as infant sleep patterns consolidated. At 3 months, 60% were in the low maternal sleep group and 40% were in the average group, while at 12 months the numbers were reversed. Most of those who were in the average sleep group at 3 months continued to be so throughout the study period.

The researchers found that an earlier bedtime and consistent routines were associated with better sleep patterns, corroborating a previous study from Fiese and Cai.

“If parents can establish early bedtime routines at three months, it improves sleep duration and reduces sleep problems,” Fiese said. “Parents may feel overwhelmed and don’t realize that they have this in their toolkit. Something as simple as setting a regular bedtime early on and having routines, like reading a story to your child before they go to bed. You may not think they’re understanding, but the rhythm of your voice establishes predictability, and you can expand this bedtime routine over the first few years of life.”

The researchers noted they did not observe any significant differences due to demographic characteristics in the sample.

“Maternal education, income, or ethnicity did not predict sleep group memberships across 3 to 24 months; all parents were facing similar challenges. I think having a baby is a great equalizer for a lot of things, although moms who have to go back to work or work longer hours may have more pressures,” Donovan said.

Even so, there are steps everyone can take to improve bedtime habits and sleep patterns.

“Getting kids to bed earlier and trying to meet the American Academy of Pediatrics guidelines is really important because studies have shown that sleep is associated with a lot of neurocognitive outcomes and health in kids. The parents can be quite proactive even early in life to get their kids off on the right foot,” she concluded.