Culture

Heart attack, or myocardial infarction, is one of the leading causes of death worldwide. Although modern surgical techniques, diagnostics and medications have greatly improved early survival from these events, many patients struggle with the long-term effects of permanently damaged tissue, and the 5-year mortality rate remains high. Now, researchers reporting in ACS Nano have developed a minimally invasive exosome spray that helped repair rat hearts after myocardial infarction.

Scientists have explored using stem cell therapy as a way to regrow tissue after a heart attack. But introducing stem cells directly to the heart can be risky because they could trigger an immune response or grow uncontrollably, resulting in a tumor. Therefore, researchers have tried injecting exosomes -- membrane-bound sacs containing proteins, lipids and nucleic acids secreted by stem cells -- into the heart, but they often break down before they can have therapeutic effects. Others have developed cardiac patches, or scaffolds that help implanted exosomes last longer, but they usually must be placed on the heart during open-chest surgery. Yafeng Zhou and colleagues wanted to develop an exosome solution that could be sprayed onto the heart through a tiny incision, avoiding major surgery.

The researchers mixed exosomes from mesenchymal stem cells with fibrinogen, a protein involved in blood clotting. They added this solution to a tiny, double-barreled syringe that contained a separate solution of another clotting protein called thrombin. When the team sprayed the solutions out of the syringe onto a rat's heart through a small chest incision, the liquids mixed and formed an exosome-containing gel that stuck to the heart. A mini-endoscope, inserted through a second small incision, guided the spray needle. In rats that had recently had a heart attack, the exosome spray lasted longer, healed injuries better and boosted the expression of beneficial proteins more than heart-injected exosomes. In pigs, the spray caused less severe immune reactions and surgical stress than open-chest surgery. The spray is a promising strategy to deliver therapeutic exosomes for heart repair, the researchers say.

Given the aging world population, there is international interest in helping older people live longer and healthier lives. Avoiding unplanned hospital admissions is an important aspect of care for older people. Palapar et al focused on the way primary care practice characteristics influence outcomes such as unplanned hospitalizations, function and well-being. They investigated the variability in older people's outcomes by primary care physician and practice characteristics in New Zealand and the Netherlands. Findings revealed that none of the physician or practice characteristics were significantly associated with rates of unplanned admissions in the New Zealand sample. In contrast, in the Netherlands sample, researchers found higher rates of admissions in large practices and practices staffed with a practice nurse who typically works in the primary care setting with general practitioners. Practice nurses are common in primary care practices in New Zealand but are relatively new and only in a portion of practices in the Netherlands, the authors note. It is unclear if these associations are causal or if the increase in hospitalizations represent higher or lower quality care. Considering these findings, the authors conclude that the central focus of international health policies on reducing hospital overuse should approach primary health care structural reform carefully.

More than 40% of physicians in the United States reported at least one symptom of burnout, which is particularly high among family physicians. This study examined a nationally-representative sample of family physicians to determine whether physician race-ethnicity was associated with burnout among a nationally-representative sample of family physicians. Of the 3,0916 physicians studied, 450 (15%) were from racial-ethnic groups underrepresented in medicine (UIM), which include Blacks/African Americans, Hispanics/Latinos, American Indians and Pacific Islanders who together comprise 30-35% of the general population yet account for only 12.4% of family physicians. The study findings support the researchers' hypothesis that UIMs were significantly less likely than their non-UIM counterparts to report emotional exhaustion and depersonalization. This may be attributed to practicing in more racially-diverse counties and being less likely to practice obstetrics, both of which partially mediated the protective effect of UIM status on depersonalization. The mediating effect of working in more racially and ethnically diverse counties is consistent with evidence of the beneficial effect of cultural diversity on health outcomes for minorities and better overall self-rated health among adults. Understanding the attributes of UIMs that may prevent burnout may also provide insights for developing a more resilient physician workforce.

BIRMINGHAM, Ala. - Uveal melanoma, or UM, is a rare and deadly cancer of the eye, and the mortality rate has remained unimproved for 40 years. Half of the melanomas spread to other organs of the body, causing death in less than a year, so new treatments to preserve vision and prevent death are an urgent need.

Now a preclinical study by researchers at the University of Alabama at Birmingham and Emory University, Atlanta, offers hope -- a small molecule inhibitor has been identified that dampens the potent drivers of this tumor. In mouse models, the inhibitor, KCN1, strongly limited primary disease in the eye and metastatic tumor dissemination to the liver, and animals survived longer, without overt side effects.

Thus, this class of inhibitory compounds shows promise, though the co-leaders of the research -- Erwin Van Meir, Ph.D., professor of neurosurgery at UAB, and Hans Grossniklaus, M.D., MBA, professor of ophthalmic pathology at Emory -- say the drug needs further optimization before clinical use.

"Overall," they wrote in the paper published in the journal Oncogene, "our preclinical studies support the further translation of the KCN1 arylsulfonamide scaffold toward a novel treatment for patients with metastatic uveal melanoma." The uvea is the pigmented layer of the eye.

Prior to this study, it was known that: 1) a hypoxia gene signature, indicative of low oxygen levels in the tumor, is associated with poor prognosis and a high metastatic rate in uveal melanoma; 2) the hypoxia-inducible transcription factor, or HIF, turns on a large number of gene products with critical roles in cancer growth and metastasis; and 3) for UM specifically, HIF promotes tumor progression by regulating proliferation, migration, invasion and adhesion of tumor cells, as well as promoting blood vessel growth to feed the tumor.

Little was known of the role of HIF in directing pro-invasive extracellular matrix remodeling in UM. Changes in the extracellular matrix, including increased collagen deposition and reorganization of collagen fibers outside the cell, is known to aid cancer progression and tumor cell invasion. Extracellular matrix is the non-cellular component of all tissues that provides physical scaffolding for cells and has other biochemical roles.

Hypoxia promotes collagen deposition, in part, because HIF increases production of two gene products, P4HA1 and P4HA2, that are part of an enzyme complex that adds hydroxyl residues to prolines in procollagen. Procollagen is a precursor protein in the complex maturation process that collagen undergoes.

In their study, Van Meir, Grossniklaus and colleagues decided to evaluate the expression of the P4HA1/2 genes in relation to UM patient prognosis, and to determine whether inhibiting hypoxia-induced P4HA1/2 expression in a preclinical model of metastatic UM would yield therapeutic benefit.

They found that P4HA1 and P4HA2 were induced by hypoxia in human UM cell lines, and this induction was reduced by KCN1. Comparison of 46 patients with non-metastatic UM and 46 with metastatic UM showed that P4HA1/2 were significantly overexpressed in patients with metastatic disease. Also, P4HA1/2 expression correlated with poor overall survival in UM patients. This suggests that P4HA1 and P4HA2 can serve as prognostic markers in UM, and that they may be important for malignant progression of the disease and patient survival.

The researchers next turned to preclinical animal models of UM. They showed that KCN1 was abundantly taken up in the liver and the eyes after intraperitoneal injection, and it dampened tumor growth and disease burden at the primary site of the eye, as well as reduced distant metastases in the liver. KCN1 also increased survival in three different models that test the growth of human UM after injection in mice uvea. The inhibitor was most effective at reducing metastases when it was administered early.

At the molecular level, treatment with KCN1 to inhibit the hypoxic induction of P4HA1/2 decreased the hydroxylation of proline amino acids in the procollagen. It also caused cleavage of the collagen and disordered the structure of collagen VI, a mature structural component of the extracellular matrix. These collagen changes correlated with a reduction in tumor cell invasion.

"Our study," Van Meir and Grossniklaus concluded, "suggests that KCN1 has desirable properties as a suppressor of metastasis: It is well tolerated, has excellent distribution to the eye and the liver, and is thus ideally suited for treating metastatic UM."

Male seed beetles with genital structures that injure females may have greater reproductive success. As new research from Uppsala University shows, females that mate with such males benefit, in the sense that their offspring are healthier. This new piece of the puzzle will help scientists to understand how complex mating interactions between males and females have developedevolved. The study is published in Proceedings of the Royal Society B.

"This helps us understand is connected with the evolutionary dance between males and females of all animal species, and the resulting differences between them - sexual dimorphism - that we observe. It's important to understand this evolutionary dance that we're all caught up in. We can show that this intricate process is influenced and governed by several different processes at the same time," says Göran Arnqvist, Professor of Animal Ecology at Uppsala University's Department of Ecology and Genetics.

The evolved mechanisms behind successful mating interactions between the sexes are complicated, and have developed throughout evolution. In insects, for example, it is not uncommon for males to have developed spiny reproductive organs that confer greater success in reproduction but simultaneously inflict harm on the females' reproductive tract in the course of mating.

In their study, the researchers bred various strains of the seed beetle (Callosobruchus maculatus). In some strains the males had mating organs with large spines, while in others thhese spines were small. When the male beetles were then mated with females, it turned out that the males with the longest thorns spines also had the greatest success with the opposite sex, despite the females suffering severe injuries during the mating. Despite these injuries, however, the females also benefited from mating with these males since their offspring, male and female alike, apparently became more viable. The existence of a genetic link between big spines and good genes was demonstrated by the fact that the sisters of the males with the longest spines were in better health than other females .

The researchers also investigated what happened if the spines were peeled off the mating organs by means of a microlaser. The males' ability to mate then deteriorated, which indicates that the number of young a male beetle can produce is not solely dependent on his genes.

"Our experiments indicate that the females do pay a high price for mating with successful males -getting injured - but also that the females simultaneously obtain genetic advantages for their offspring. Our results provide support for a more nuanced view of mating interactions in the animal world, where behaviours can be shaped by several effects, and seemingly different evolutionary forces, at the same time," Arnqvist says.

A new study led by the U.S. Geological Survey outlines a means to better estimate COVID-19 occurrence and trends in populations.

Currently, COVID-19 testing is primarily limited to self-selected individuals, many of whom are symptomatic or have had contact with someone who is symptomatic. While these tests are useful for individual medical treatment and contact tracing, they do not provide health officials with a complete picture of the disease across the population.

"Coordinated sampling of COVID-19 is key to informing health officials as they continue their efforts to control the pandemic, permitting better predictions of disease dynamics and decisions that help limit transmission," said James Nichols, USGS scientist emeritus and lead author of the study. "The proposed sampling methods should also help officials determine the effectiveness of vaccines, social distancing, masks and other mitigation efforts."

By bringing its unique expertise in the design of data-gathering and monitoring systems, statistical analysis and mathematical modeling to human epidemiology, the USGS provides a means to fill the current information gap in testing data. This can benefit national and local governments and health officials as they develop interventions in response to new disease variants, plan for augmented vaccination efforts and prepare for future outbreaks.

With some countries experiencing surges in cases, Nichols points out, "the proposed testing strategies can be applied within the U.S. and internationally for COVID-19 and other diseases."

One proposal in the study is to select a random sample within a population and survey those individuals for symptoms, such as elevated temperature, in order to gather more representative data on asymptomatic cases. This would help researchers estimate the proportion of symptomatic and asymptomatic individuals in the population.

The asymptomatic individuals, or a random subset of those individuals, could be tested for COVID-19 to help estimate infection probability for asymptomatic individuals in the population.

"The strategies outlined in this new research would help strengthen current testing approaches and could be done with relatively few additional tests and non-invasive surveys," said Michael Runge, a USGS scientist and a co-author of the study. "Strategic testing, based on specific objectives, can provide information valuable for decisions about both individual healthcare and protecting communities."

"It is critically important to be clear about the goal of a surveillance program," said co-author Katriona Shea, a professor of biology and alumni professor in the biological sciences at Penn State. "Without knowing exactly what you want to achieve, how can you achieve it? A surveillance program for individual outcomes would be designed differently than a program aimed to understand population level public health objectives."

BUFFALO, N.Y. - Write down the benefits of obtaining a college degree and, more than likely, all the items on the completed list will relate to graduates: higher salaries, autonomous jobs and better access to health care, for instance. All of those factors, supported by extensive research, help draw a direct line connecting higher education and health. Similar research suggests how the education of parents affects their children.

Now, two University at Buffalo sociologists have used a new wave of data from a survey launched in 1994 to further extend the geometry linking educational attainment and health that demonstrates another dimension of the intergenerational effects of completing college. Their findings published recently in the Journal of Gerontology: Social Sciences suggest that adult children's educational attainment has an impact on their parents' mental and physical health.

"By analyzing these data we arrived at the conclusion that it was detrimental to parents' self-reported health and depressive symptoms if none of their children completed college," says Christopher Dennison, PhD, assistant professor of sociology in UB's College of Arts and Sciences, and a co-author of the paper with UB colleague Kristen Schultz Lee, PhD, an associate professor in the Department of Sociology. "The negative mental health outcome of the parents was in fact our strongest finding."

Dennison and Lee have both used the National Longitudinal Study of Adolescent to Adult Health (Add Health) in their previous research. Add Health is a nationally representative longitudinal study of over 20,000 adolescents. It is the largest such survey of its kind. There was an initial wave of data on the parents (ages 30-60) when the survey began and another wave of data from roughly 2,000 of those original participants (now ages 50-80) gathered from 2015-17.

It's this latter data set that provided the researchers an opportunity to look at the intergenerational relationship between parents and children over time, while statistically balancing factors that could influence an aging parent's health.

"These results are particularly important in light of growing educational inequalities in the U.S. in the last several decades," says Lee. "We know how our own education impacts our own health; we know how parents' education impacts their children in many different ways; now we're trying to add to that understanding by explaining how children's education can have an impact on their parents.

"One thing I thought particularly interesting about these findings is that those parents who are the least likely to have a child attain a college education (low socioeconomic status) seem to benefit the most from a child having a college degree."

Dennison and Lee speculate on a number of elements that might be driving this association, including anxiety, assistance and lifestyle.

"Parents whose children have lower levels of education might spend more time worrying about their children. That has negative implications for their mental health and their self-rated health," says Lee. "Kids without a degree might need more help from their parents and are also less able to provide help if needed in return.

"Another possibility is that educated children might be doing a better job of helping their parents live healthier lives by encouraging exercise and a sensible diet."

What's clear is the evidence pointing to how the benefits of a college degree show up in the parents' health later in life.

"In this era when a college degree is of ever-growing importance, we see how the long-term investment in education is advantageous to the adult child's health, but also has benefits down the road for their parents too," says Dennison.

And it's this idea of an investment that speaks to how educational attainment reaches across generations from a policy perspective.

"Historically, there has been a debate over whether or not different generations are at odds with one another, with one generation taking resources away from another older or younger generation," says Lee. "But our findings point to the fundamentally inter-related nature of the interests and needs of different generations.

"Investing in one generation, in this case, positively benefits another generation."

Hundreds of millions of people live on river deltas around the world, making them central to rich diversity in culture and thriving economies. As deltas face environmental degradation and ongoing climate change, governments have sought ever more drastic measures to prevent flooding and protect society and its infrastructure. But, these policies can harm the natural environment and lead to loss of precious land. Striking a balance between limiting deltaic land loss and maximizing cultural and economic benefit to society is a top priority in sustainability policy.

Researchers at The University of Texas at Austin and Texas Tech University created a novel analysis tool that seeks to protect the millions of people living on urban river deltas, while preserving the environmental and commercial viability of these landscapes. Their study, published recently in Proceedings of the National Academy of Sciences, applies a cost-benefit model to the concept of delta management, for the first time, by examining how to balance the natural function of river deltas with societal desire for landscape stability.

"By restricting river channels on deltas, we have limited the delivery of sediment to the coast where it is needed to sustain land in the face of rising sea level," said Andrew Moodie, lead author of the paper and a National Science Foundation Postdoctoral Research Fellow working in associate professor Paola Passalacqua's lab in the Department of Civil, Architectural and Environmental Engineering in the Cockrell School of Engineering. "The irony here is that by preventing the river from flooding naturally, we have exacerbated land loss, and in the long run, made society more susceptible to catastrophic floods."

In their paper, the researchers note that levees and other flood prevention measures are often placed near the coast because it costs less and minimizes the impact on major population centers. But these downstream locations restrict the natural function of delta land building, which requires sediment to reach the coast.

Moodie's study leverages recent scientific advancements from two highly populated deltas, the Yellow River in China and the Mississippi River, to investigate nature-based solutions that mimic how rivers naturally behave to stop land loss. They analyzed the best location for channel diversions, which are engineered structures that create new pathways for rivers to flow through. Finding the right placement required balancing the benefits of diversions in terms of land building, with the cost of the structure. The balance of costs and benefits will vary with every delta, so there is no one catchall answer. However, the framework can be applied to a variety of systems worldwide.

The analysis found that to maximize the efficacy of diversions, structures need to be placed farther upstream than existing designs and structures, which are often away from population centers and near the coast. The tradeoff with building diversions upstream is that it usually costs more and is more likely to displace people.

"A lot of studies have said that society, in particular major cities like New Orleans, is doomed, and that engineering efforts leveraging nature-based solutions can't coexist with large population centers," Moodie said. "What we've shown with our optimizable framework is that having cities nearby actually makes it even easier to justify doing these large projects, because they protect communities."

Moodie started this work as part of his Ph.D. studies while at Rice University. His dissertation explored the impacts of river channel avulsions on deltas -- a process by which a channel abruptly abandons its course in favor of a new pathway to the sea.

"Avulsions are quite similar to diversions that humans are trying to implement on river deltas, for the sake of nourishing the landscape," Moodie said.

Focusing on the Yellow River delta of China, Moodie recognized an unaddressed problem: a lack of research integrating geomorphology and hydrology with economics, when considering how to manage deltas with diversions.

"We as humans want stability; we want stable landscapes we can count on year after year to provide ecosystem services such as fisheries, growing beds for oysters and more," Moodie said. "All these things are impacted by natural avulsions, and if we effectively harness this behavior, we can sway the scale to better the chances of sustaining deltas and the people and cultures that exist there."

Glenview, Illinois - The American College of Chest Physicians® (CHEST) recently released a new clinical guideline, Screening for Lung Cancer: CHEST Guideline and Expert Panel Report. The guideline contains 16 evidence-based recommendations and an update of the evidence base for the benefits, harms, and implementation of low-dose chest computed tomography (CT) screening.

Lung cancer is by far the leading cause of cancer death among both men and women, making up almost 25% of all cancer deaths. Evidence suggests that low-dose CT screening for lung cancer can reduce cancer-related deaths in the group that is screened. The new guidelines provide recommendations on the selection of screen-eligible individuals, the quality of imaging and image interpretation, the management of screen detected findings and the effectiveness of smoking cessation interventions.

"The goal of these guidelines is to assist stakeholders with the development of high-quality screening programs and arm clinical providers with the information necessary to engage at-risk individuals in order to increase the number of screenings," says lead author Peter Mazzone, MD, MPH, FCCP. "Outlined in the recommendations is who should be screened and what that screening process should look like from the clinical side. For an individual patient, these guidelines highlight the importance of education to foster informed, value-based decisions about whether to be screened."

Of the 16 recommendations, the guidelines presented in the report include the following:

· For asymptomatic individuals aged 50 to 80 who have smoked 20 pack years or more and either continue to smoke or have quit within the past 15 years, we recommend that annual screening with low-dose CT should be offered.

· We suggest that low-dose CT screening programs develop strategies to maximize compliance with annual screening exams and evaluation of screen detected findings.

· For individuals who currently smoke and are undergoing low-dose CT screening, we recommend that screening programs provide evidence-based tobacco cessation treatment as recommended by the U.S. Public Health Service.

The full list of recommendations can be found here.

One of the requirements for Medicare coverage of lung cancer screening is that a beneficiary has a lung cancer screening counseling and shared decision-making (SDM) visit. The goal of shared decision-making is to inform individuals about the tradeoffs of screening vs. not screening and to help them make a choice that is aligned with their preferences and values. For training on shared decision-making, CHEST and Thomas Jefferson University offer a course dedicated to guiding patients through the decision to be screened for lung cancer. For more information on the course, visit the CHEST website.

Professors in Syracuse University's College of Arts and Sciences explored whether or not the scientific community will ever be able to settle on a 'total number' of species of living vertebrates, which could help with species preservation. By knowing what's out there, researchers argue that they can prioritize places and groups on which to concentrate conservation efforts.

Research professor Bruce Wilkinson and professor Linda Ivany, both from the Department of Earth and Environmental Sciences, recently co-authored a paper in the Biological Journal of the Linnean Society where they determined that forecasting the total number of species may never be possible.

When asking the question, 'how many species?,' it is important to note that only a fraction of existing species have been named. In order to make a prediction on a total number, researchers project the curve of new species descriptions each year into the future until eventually reaching a point when all species should have been found.

Wilkinson, a geologist, noticed parallels between the discovery curves of new species and the total reservoir size of nonrenewable resources like oil or mineral ores. Similar to the species curve, by extending the oil reservoir curve researchers thought they should be able to estimate the total global reservoir and how long it will take to get to it all. The theory of resource exploitation suggests that the number of discoveries over time follows a bell-shaped curve: The curve rises as production rate increases due to new discoveries and then decreases as production declines, despite all the effort continuing to go into finding the resource. The time of maximum discovery is known as Hubbert's peak, after M. King Hubbert who predicted it. Following that time, the resource is being evermore depleted until it is used up.

"The problem with using that curve to predict how much is left is that you have to assume that the effort invested and the approach used to discover new oil, or species, is consistent and known," says Wilkinson. "We used to think we'd gone over the peak for oil and gas around 1972, but then 15 or so years ago someone figured out how to do horizontal drilling and all of the sudden there was a new bump in the amount being discovered."

Wilkinson and Ivany say that the discovery curve for new species of vertebrate animals shows a similar bump. Like the increase in the oil curve caused by horizontal drilling in the early 2000s, there was a surge in new species discovery beginning around 1950, when new funding was being dedicated to science after the World War II, more scientists were going into biology, and new molecular techniques were leading to an increase in the ability to distinguish species from one another.

In both cases, unforeseen changes in the effort and method of discovering new oil or species altered the way the discovery curves were playing out.

If researchers had estimated the total number of species based on data prior to 1950, their estimates would be much different from any estimate made today, and both would likely be wrong because those new advents cannot be predicted.

In some ways, this is a reflection of the scientific method, in which hypotheses stand until new facts are discovered, which lead to changes in the hypothesis.

"As much as we'd like to know 'the number,' the total species richness of the planet will remain an elusive target," says Ivany.

Researchers at UC San Francisco have successfully developed a "speech neuroprosthesis" that has enabled a man with severe paralysis to communicate in sentences, translating signals from his brain to the vocal tract directly into words that appear as text on a screen.

The achievement, which was developed in collaboration with the first participant of a clinical research trial, builds on more than a decade of effort by UCSF neurosurgeon Edward Chang, MD, to develop a technology that allows people with paralysis to communicate even if they are unable to speak on their own. The study appears July 15 in the New England Journal of Medicine.

"To our knowledge, this is the first successful demonstration of direct decoding of full words from the brain activity of someone who is paralyzed and cannot speak," said Chang, the Joan and Sanford Weill Chair of Neurological Surgery at UCSF, Jeanne Robertson Distinguished Professor, and senior author on the study. "It shows strong promise to restore communication by tapping into the brain's natural speech machinery."

Each year, thousands of people lose the ability to speak due to stroke, accident, or disease. With further development, the approach described in this study could one day enable these people to fully communicate.

Translating Brain Signals into Speech

Previously, work in the field of communication neuroprosthetics has focused on restoring communication through spelling-based approaches to type out letters one-by-one in text. Chang's study differs from these efforts in a critical way: his team is translating signals intended to control muscles of the vocal system for speaking words, rather than signals to move the arm or hand to enable typing. Chang said this approach taps into the natural and fluid aspects of speech and promises more rapid and organic communication.

"With speech, we normally communicate information at a very high rate, up to 150 or 200 words per minute," he said, noting that spelling-based approaches using typing, writing, and controlling a cursor are considerably slower and more laborious. "Going straight to words, as we're doing here, has great advantages because it's closer to how we normally speak."

Over the past decade, Chang's progress toward this goal was facilitated by patients at the UCSF Epilepsy Center who were undergoing neurosurgery to pinpoint the origins of their seizures using electrode arrays placed on the surface of their brains. These patients, all of whom had normal speech, volunteered to have their brain recordings analyzed for speech-related activity. Early success with these patient volunteers paved the way for the current trial in people with paralysis.

Previously, Chang and colleagues in the UCSF Weill Institute for Neurosciences mapped the cortical activity patterns associated with vocal tract movements that produce each consonant and vowel. To translate those findings into speech recognition of full words, David Moses, PhD, a postdoctoral engineer in the Chang lab and lead author of the new study, developed new methods for real-time decoding of those patterns, as well as incorporating statistical language models to improve accuracy.

But their success in decoding speech in participants who were able to speak didn't guarantee that the technology would work in a person whose vocal tract is paralyzed. "Our models needed to learn the mapping between complex brain activity patterns and intended speech," said Moses. "That poses a major challenge when the participant can't speak."

In addition, the team didn't know whether brain signals controlling the vocal tract would still be intact for people who haven't been able to move their vocal muscles for many years. "The best way to find out whether this could work was to try it," said Moses.

The First 50 Words

To investigate the potential of this technology in patients with paralysis, Chang partnered with colleague Karunesh Ganguly, MD, PhD, an associate professor of neurology, to launch a study known as "BRAVO" (Brain-Computer Interface Restoration of Arm and Voice). The first participant in the trial is a man in his late 30s who suffered a devastating brainstem stroke more than 15 years ago that severely damaged the connection between his brain and his vocal tract and limbs. Since his injury, he has had extremely limited head, neck, and limb movements, and communicates by using a pointer attached to a baseball cap to poke letters on a screen.

The participant, who asked to be referred to as BRAVO1, worked with the researchers to create a 50-word vocabulary that Chang's team could recognize from brain activity using advanced computer algorithms. The vocabulary - which includes words such as "water," "family," and "good" - was sufficient to create hundreds of sentences expressing concepts applicable to BRAVO1's daily life.

For the study, Chang surgically implanted a high-density electrode array over BRAVO1's speech motor cortex. After the participant's full recovery, his team recorded 22 hours of neural activity in this brain region over 48 sessions and several months. In each session, BRAVO1 attempted to say each of the 50 vocabulary words many times while the electrodes recorded brain signals from his speech cortex.

Translating Attempted Speech into Text

To translate the patterns of recorded neural activity into specific intended words, Moses's two co-lead authors, Sean Metzger and Jessie Liu, both bioengineering graduate students in the Chang Lab, used custom neural network models, which are forms of artificial intelligence. When the participant attempted to speak, these networks distinguished subtle patterns in brain activity to detect speech attempts and identify which words he was trying to say.

To test their approach, the team first presented BRAVO1 with short sentences constructed from the 50 vocabulary words and asked him to try saying them several times. As he made his attempts, the words were decoded from his brain activity, one by one, on a screen.

Then the team switched to prompting him with questions such as "How are you today?" and "Would you like some water?" As before, BRAVO1's attempted speech appeared on the screen. "I am very good," and "No, I am not thirsty."

Chang and Moses found that the system was able to decode words from brain activity at rate of up to 18 words per minute with up to 93 percent accuracy (75 percent median). Contributing to the success was a language model Moses applied that implemented an "auto-correct" function, similar to what is used by consumer texting and speech recognition software.

Moses characterized the early trial results as a proof of principle. "We were thrilled to see the accurate decoding of a variety of meaningful sentences," he said. "We've shown that it is actually possible to facilitate communication in this way and that it has potential for use in conversational settings."

Looking forward, Chang and Moses said they will expand the trial to include more participants affected by severe paralysis and communication deficits. The team is currently working to increase the number of words in the available vocabulary, as well as improve the rate of speech.

Both said that while the study focused on a single participant and a limited vocabulary, those limitations don't diminish the accomplishment. "This is an important technological milestone for a person who cannot communicate naturally," said Moses, "and it demonstrates the potential for this approach to give a voice to people with severe paralysis and speech loss."

As the Parker Solar Probe ventures closer to the sun, we are learning new things about our home star.

In a new study, physicists led by the University of Iowa report the first definitive measurements of the sun's electric field, and how the electric field interacts with the solar wind, the fast-flowing current of charged particles that can affect activities on Earth, from satellites to telecommunications.

The physicists calculated the distribution of electrons within the sun's electric field, a feat made possible by the fact that the Parker Solar Probe jetted within 0.1 astronomical units (AU), or a mere 9 million miles, from the sun--closer than any spacecraft has approached. From the electrons' distribution, the physicists were able to discern the size, breadth, and scope of the sun's electric field more clearly than had been done before.

"The key point I would make is you can't make these measurements far away from the sun. You can only make them when you get close," says Jasper Halekas, associate professor in the Department of Physics and Astronomy at Iowa and the study's corresponding author. "It's like trying to understand a waterfall by looking at the river a mile downstream. The measurements we made at 0.1 AU, we're actually in the waterfall. The solar wind is still accelerating at that point. It's really just an awesome environment to be in."

The sun's electric field arises from the interaction of protons and electrons generated when hydrogen atoms are stripped apart in the intense heat generated by fusion deep within the sun. In this environment, electrons, with masses 1,800 times less than that of protons, are blown outward, less constrained by gravity than their weightier proton siblings. But the protons, with their positive charge, exert some control, reining in some electrons due to the familiar attraction forces of oppositely charged particles.

"Electrons are trying to escape, but protons are trying to pull them back. And that is the electric field," says Halekas, a co-investigator for the Solar Wind Electrons, Alphas, and Protons instrument aboard the Parker Solar Probe, the NASA-led mission that launched in August 2018. "If there were no electric field, all the electrons would rush away and be gone. But the electric field keeps it all together as one homogenous flow."

Now, imagine the sun's electric field as an immense bowl and the electrons as marbles rolling up the sides at differing speeds. Some of the electrons, or marbles in this metaphor, are zippy enough to cross over the lip of the bowl, while others don't accelerate enough and eventually roll back toward the bowl's base.

"We are measuring the ones that come back and not the ones that don't come back," Halekas says. "There's basically a boundary in energy there between the ones that escape the bowl and the ones that don't, which can be measured. Since we're close enough to the sun, we can make accurate measurements of electrons' distribution before collisions occur further out that distort the boundary and obscure the imprint of the electric field."

From those measurements the physicists can learn more about the solar wind, the million-mile-per-hour jet of plasma from the sun that washes over the Earth and other planets in the solar system. What they found is the sun's electric field exerts some influence over the solar wind, but less than had been thought.

"We can now put a number on how much of the acceleration is provided by the sun's electric field," Halekas says. "It looks like it's a small part of the total. It's not the main thing that gives the solar wind its kick. That then points to other mechanisms that might be giving the solar wind most of its kick."

The paper, "The sunward electron deficit: A telltale sign of the sun's electric potential," was published online July 14 in The Astrophysical Journal.

PHOENIX, Ariz. -- July 14, 2021 -- The results of a study by an international scientific team co-led by the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, suggest that -- like pouring water atop a wellhead before pumping -- the airway cells of patients with chronic lung diseases are "primed" for infection by the COVID-19 virus, resulting in more severe symptoms, poorer outcomes and a greater likelihood of death.

The study -- published today in Nature Communications -- details the genetic changes caused by chronic lung disease in the molecular makeup of a variety of cells, including the epithelial cells that line the lung and airways. The study details how those changes can help enable SARS-CoV-2, the virus that causes COVID-19, to enter the body, replicate and trigger an out-of-control immune response that fills the lungs with fluids and often results in patients needing respirators and lengthy hospitalizations.

The team used single-cell RNA sequencing technology to spell out the genetic code of 611,398 cells from various data bases, representing those with both healthy (control) lungs and those with chronic lung disease. Sequencing and analysis allowed researchers to identify molecular characteristics that may account for worse COVID-19 outcomes.

"Our results suggest that patients with chronic lung disease are molecularly primed to be more susceptible to infection by SARS-CoV-2," said Nicholas Banovich, Ph.D., an Associate Professor in TGen's Integrated Cancer Genomics Division, and one of the study's senior authors. Dr. Banovich is a leading participant in the Human Cell Atlas Lung Biological Network, whose dozens of members, representing more than 80 institutions worldwide, also contributed to this study.

In addition, older-age, male-gender, smoking, and comorbidities such as high blood pressure, obesity and diabetes, are all COVID-19 risk factors that are exacerbated by chronic lung diseases, such as Chronic Obstructive Pulmonary Disease (COPD), Interstitial Lung Disease (ILD), and especially Idiopathic Pulmonary Fibrosis (IPF), a progressive scaring and stiffening of the lung tissue.

"It was recognized early in the pandemic that patients with chronic lung diseases were at particularly high risk for severe COVID-19, and our goal was to gain insight into the cellular and molecular changes responsible for this," said Jonathan Kropski, M.D., Associate Professor of Medicine and Cell and Developmental Biology at Vanderbilt University Medical Center, and a co-senior author of the study.

Changes in lung cells and immune cells

Researchers specifically searched for changes in AT2 cells, a major lung epithelial cell type, focusing on cellular pathways and expression levels of genes associated with COVID-19. They established a "viral entry score," a composite of all genes associated with SARS-CoV-2, and found higher scores among cells from patients with chronic lung disease.

They also explored changes in immune cells and discovered dysregulated gene expression associated with hyper-inflammation and with sustained cytokine production, two signature symptoms of severe SARS-CoV-2 infection. So-called cytokine storms in COVID-19 patients unleash a cascade of immune cells that flood the lungs, causing severe organ damage.

"The genetic changes in immune cells, especially in specialized white blood cells known as T cells, may diminish the patient's immune response to viral infection and lead to higher risk of severe disease and poor outcomes in patients with chronic lung disease," said Linh Bui, Ph.D., a post-doctoral fellow in Dr. Banovich's lab, and one of the study's lead authors.

"Our data suggest that the immune microenvironment at both the molecular and cellular levels in lungs damaged by chronic diseases may promote severe COVID-19," Dr. Bui said.

Significant contributions to this study were made by: Vanderbilt University Medical Center, Yale School of Medicine, Harvard Medical School, Baylor College of Medicine, and the Department of Veterans Affairs Medical Center. Plus several institutes in the UK, including: London's Imperial College, Royal Brompton and Harefield National Health System Foundation Trust, Edinburgh University Medical School, and the Royal Infirmary of Edinburgh.

The extraordinary ability of animals to rapidly evolve in response to predators has been demonstrated via genetic sequencing of a waterflea population across nearly two decades.

In a new study, published in Nature Communications, scientists at the Universities of Birmingham in the UK, the Katholieke Universiteit Leuven in Belgium, and the Leibniz Institute for Freshwater Ecology and Inland Fisheries (IGB), Berlin, were able to identify more than 300 genes that vary in the genome of the waterflea.

These genes, which account for about about 3 per cent of all sequenced waterflea genes, underpin changes in behavioural and life history traits that improve survival when exposed to predators.

Strikingly, evolution in response to predation pressure occurs within just a few generations. It is mediated by so-called standing genetic variation - the amount of genetic diversity harboured by a given natural population. The research brings to the forefront of science the importance of standing genetic diversity to support rapid adaptation. It also highlights that reducing the genetic diversity of natural populations has important consequences for their ability to adapt to environmental change.

Lead researcher, Dr Anurag Chaturvedi, currently at the University of Birmingham's School of Biosciences and former PhD student at KU Leuven, explained: "We were able to quantify the genetic diversity of one particular Daphnia population over nearly two decades and show clearly how rapid evolution took place in response to environmental pressures. This type of research will be invaluable for understanding the potential impacts of future environmental changes on animal populations."

The waterflea, or Daphnia, is central to the food webs of lakes and ponds. Its life cycle includes a dormant stage that can last for several decades. By awakening dormant stages through resurrection biology, scientists can quantify genetic changes at several time points in the past and observe evolution as it happens in nature.

In the study, the team was able to hatch dormant eggs that span two decades and to sequence the genome of 36 resurrected Daphnia from a fish-farming pond. During the two decades, the Daphnia population experienced a transition from no predation from fish to high fish predation and back to lower levels of predation. The team was able to uniquely match changes in predation pressure on Daphnia with changes in the DNA over time. In effect, the research was able to link specific changes in the environment of Daphnia with the evolution occurring in their genomes.

The team found that the required DNA variation to kick-start an evolutionary change that spreads through an entire population did not require more than five 'founding' individual Daphnia from the regional set of Daphnia populations.

This surprising result suggests that animal species such as Daphnia have a high capacity for adaptive evolution thanks to the fact that genetic variation is maintained at the landscape level - an important lesson for conservation biology.

Lead researcher, Dr Anurag Chaturvedi explained: "Our ability to investigate populations that evolve across decades is invaluable for both fundamental and applied science discoveries".

July 14, 2021 (Toronto) A new study from the World Health Organization's (WHO) International Agency for Research on Cancer (IARC), published in the journal Lancet Oncology, has found an association between alcohol and a substantially higher risk of several forms of cancer, including breast, colon, and oral cancers. Increased risk was evident even among light to moderate drinkers (up to two drinks a day), who represented 1 in 7 of all new cancers in 2020 and more than 100,000 cases worldwide.

In Canada, alcohol use was linked to 7,000 new cases of cancer in 2020, including 24 per cent of breast cancer cases, 20 per cent of colon cancers, 15 per cent of rectal cancers, and 13 per cent of oral and liver cancers.

"All drinking involves risk," said study co-author Dr. Jürgen Rehm, Senior Scientist, Institute for Mental Health Policy Research and Campbell Family Mental Health Research Institute at CAMH. "And with alcohol-related cancers, all levels of consumption are associated with some risk. For example, each standard sized glass of wine per day is associated with a 6 per cent higher risk for developing female breast cancer."

"Alcohol consumption causes a substantial burden of cancer globally," said Dr. Isabelle Soerjomataram, Deputy Branch Head, Cancer Surveillance Branch at IARC. "Yet the impact on cancers is often unknown or overlooked, highlighting the need for implementation of effective policy and interventions to increase public awareness of the link between alcohol use and cancer risk, and decrease overall alcohol consumption to prevent the burden of alcohol-attributable cancers."

Dr. Leslie Buckley, CAMH Chief of Addictions, added: "In our clinic we are seeing many people who report increased alcohol use since the onset of the pandemic. Although this may be related to temporary stressors, there is a potential for new habits to become more permanent. The consequences with alcohol use are often subtle harms initially that take time to show themselves, while long-term consequences such as cancer, liver disease and substance use disorder can be devastating."

The modelling study was based on data on alcohol exposure from almost all countries of the world, both surveys and sales figures, which were combined with the latest relative risk estimates for cancer based on level of consumption.

"Alcohol causes cancer in numerous ways," explained Dr. Kevin Shield, Independent Scientist, Institute for Mental Health Policy Research, and study co-author. "The main mechanism of how alcohol causes cancer is through impairing DNA repair. Additional pathways include chronic alcohol consumption resulting in liver cirrhosis, and alcohol leading to a dysregulation of sex hormones, leading to breast cancer. Alcohol also increases the risk of head and neck cancer for smokers as it increases the absorption of carcinogens from tobacco."

Dr. Rehm says research into the link between light to moderate drinking and cancer is relatively new and that public policy does not yet reflect the degree of cancer risk. He added, "As an epidemiologist, I would recommend higher taxes to fully reflect the burden of disease from alcohol. Along with limiting the physical availability and marketing of alcohol, price controls are recognized as high-impact, cost-effective measures to reduce alcohol-related harm." Governments can also consider requiring manufacturers to include information about health and safety risks associated with alcohol consumption, including cancer risk, on alcoholic beverage labels.

These suggestions and many others can be found in CAMH's Alcohol Policy Framework. Updated in September 2019, the document proposes evidence-informed measures to effectively address the health and social harms associated with alcohol.