Culture

Researchers from University of British Columbia, Emory University, and New York University published a new paper in the Journal of Marketing that investigates the relationship between branding and counter-marketing in the cigarette industry.

The study, forthcoming in the Journal of Marketing, is titled "Investigating the Effects of Excise Taxes, Public Usage Restrictions, and Anti-Smoking Ads across Cigarette Brands" and is authored by Yanwen Wang, Michael Lewis, and Vishal Singh.

While the goal of marketing is usually to boost purchase rates and strengthen relationships between consumers and brands, counter-marketing is an increasingly common strategy for reducing the consumption of "vice" goods such as cigarettes. Counter-marketing activities may include excise taxes that increase consumer costs, usage constraints that restrict public consumption, and advertising that highlights product dangers. A notable feature of many vice categories is that they are dominated by very strong or high-equity brands such as Coca-Cola, McDonald's, Budweiser, and Marlboro.

The researchers assembled a data set that includes a consumer panel of cigarette purchases for a six-year period from 2005 to 2010, retail scanner data from 2006 to 2010, and a comprehensive data set on state-level cigarette taxes, state-level smoke-free restrictions, and national anti-smoking advertising campaigns. They modeled each smoker's monthly brand and quantity decisions and evaluated if and how cigarette excise taxes, smoke-free restrictions, and anti-smoking advertising campaigns influenced cigarette purchase decisions asymmetrically across a variety of brands and composites of brands based on price tier. The research also includes an analysis of tax passthrough, highlighting the role of brand positioning and channel characteristics.

Results show that the effects of anti-smoking interventions vary significantly across brands. Marlboro, the category leader, for example, is relatively less affected by tax increases, but relatively more affected by usage restrictions. The resistance to taxes is driven by Marlboro's ability to pass through less of the tax increases than most other brands. This effect may be due to market share based on economies of scale or distribution strength that leads retailers to limit price increases of their highest-volume brand. In the case of usage restrictions, results show that high-equity brands incur more negative effects. The researchers' speculation is that public prohibitions make it more difficult for consumers to garner symbolic or image-based benefits through consumption of high-equity brands. Regarding anti-smoking advertising, these communications have relatively little effect overall, but do have a slightly above-average impact on Marlboro.

Since cigarette excise taxes have almost doubled in the past ten years, these policy experiments may partially explain why Marlboro's market shares have increased in almost every state of the U.S. As Wang explains, "The findings highlight the importance of considering brand asymmetries when applying cigarette tax hikes and smoke-free restrictions. Strong brands such as Marlboro may be better able to resist tax hikes due to lower tax passthrough rates. However, removing public consumption options may reduce the stronger brands' value because consumers can no longer benefit from using them to project a public image."

A series of policy experiments assesses the differential effects of alternative counter-marketing policies across stakeholders including regulators, consumers, and brands. "We find that a 100% tax increase yields a 30% increase in quit rate, but it imposes significant costs to consumers and only increases tax receipts by about 28%. In contrast, an aggressive smoke-free policy increases quit rates by 9% and reduces tax revenues by 6%. With usage restrictions, consumers may experience inconvenience and reduced symbolic benefits but do not incur economic costs," says Lewis.

Overall, the simulations reveal important elements of the category structure for consumers, regulators, and brands. Increased taxes and smoke-free restrictions both decrease consumption and increase quit rates. However, taxes impose significant financial burdens on consumers while providing revenues to the government, whereas smoke-free restrictions lead to a loss in tax revenue, but do not impose economic costs on consumers. In terms of brands, stronger brands tend to gain share following tax hikes, but lose share due to smoke-free policies. The research does not find a readily identifiable pattern of the effects of anti-smoking advertising across brands. In general, these effects are small or insignificant.

Regarding other categories, Singh says that "While lessons learned from tobacco control efforts are also likely to be used when designing counter-marketing tactics in categories such as fast food or soda, these findings suggest that efforts to tax soda or fast food might result in increased market shares for high-equity brands. However, this is speculation, and additional research is needed."

Categories now targeted by anti-obesity groups include exceptionally powerful brands such as McDonald's and Coca-Cola. Public relations responses are just one option for brands facing counter-marketing. Relationships between consumers and relatively weak brands may be disrupted using taxes, while for strong brands, the appropriate tactic seems to be usage restrictions that limit public consumption. For companies in these categories, these results suggest that brand building is the correct response to taxes, while usage restrictions call for other responses, such as lobbying.

New UCLA research suggests that elderly patients of female physicians are more likely than those of male physicians in the same outpatient practice to be vaccinated against the flu.

This trend holds for all racial and ethnic groups studied and could provide insight into improving vaccination rates for influenza, COVID-19 and other illnesses, according to the research letter, which is published in the peer-reviewed JAMA Internal Medicine.

Prior studies have shown that female physicians tend to spend more time with their patients, said study author Dr. Dan Ly, an assistant professor in the division of general internal medicine and health services research at the David Geffen School of Medicine at UCLA.

"Now we're trying to vaccinate against COVID-19, and we will soon get to a point where most adults who want a vaccine will get it," Ly said. "We'll then need to reach those who need more convincing in order to be vaccinated, and my research suggests that perhaps this extra time spent may be helpful in getting these patients vaccinated.

"In general, flu vaccines are 40% to 60% effective. But COVID-19 vaccines are more than 90% effective, and even more so against severe disease," he said. "This means that the time spent to convince a patient to get vaccinated against COVID-19 is time well spent, not to mention the societal benefits coming from it."

People in some racial and ethnic groups, particularly Black people, are less likely to be vaccinated for a variety of complex reasons.

Ly examined Medicare claims data from 2006 through 2016 for both male and female beneficiaries age 65 years and older from four racial and ethnic groups: white, Black, Asian and Hispanic. The research sample about included approximately 40 million patient visits to about 150,000 female physicians and 300,000 male physicians.

Ly found that patients of female physicians were vaccinated at higher rates than those of male physicians across the board:

Among white men, the vaccination rate was 52.7% for those seen by female physicians, compared with 52.0% for male physicians. For white women, the rates were 54.6% (female physician) and 53.8% (male physician).

Rates for Black men were 39.8% vs. 38.1%; for Black women, 41.6% vs. 40.3%.

Among Asian men, rates were 56.8% vs. 54.7%; for Asian women, 56.4% vs. 55.7%.

For Hispanic man, rates were 48.9% vs. 47.3%; for Hispanic women, 50.6% vs. 49.1%.

Ly also found that female physicians were more likely than male physicians to get patients with more chronic conditions and co-mordibities vaccinated.

Overall, Black patients were about 14 percentage points less likely, and Hispanics 5 percentage points less likely, than whites to be vaccinated. Differences in vaccination rates between patients of female and male physicians, Ly found, represented 10% of the white-Black gap and about 30% of the white-Hispanic gap.

Differences in communication style between female and male physicians, which have been documented in previous studies, may also contribute to the differences vaccination rates, Ly noted.

A single footprint left by a cat-sized dinosaur around 100 million years ago has been discovered in China by an international team of palaeontologists.

University of Queensland researcher Dr Anthony Romilio was part of the team that investigated the track, originally found by Associate Professor Lida Xing from the China University of Geosciences (Beijing).

"This footprint was made by a herbivorous, armoured dinosaur known broadly as a stegosaur - the family of dinosaurs that includes the famed stegosaurus," Dr Romilio said.

"Like the stegosaurus, this little dinosaur probably had spikes on its tail and bony plates along its back as an adult.

"With a footprint of less than six centimetres, this is the smallest stegosaur footprint known in the world.

"It's in strong contrast with other stegosaur prints found at the Chinese track site which measured up to 30 centimetres, and prints found in places like Broome in Western Australia where they can be up to 80 centimetres."

The tiny footprint has similar characteristics of other stegosaur footprints with three short, wide, round toe impressions.

However researchers found the print wasn't elongated like larger counterpart prints discovered at the track sites, which suggests the young stegosaur had a different behaviour.

"Stegosaurs typically walked with their heels on the ground, much like humans do, but on all fours which creates long footprints," Dr Romilio said.

"The tiny track shows that this dinosaur had been moving with its heel lifted off the ground, much like a bird or cat does today.

"We've only previously seen shortened tracks like this when dinosaurs walked on two legs."

Associate Professor Xing said that it was plausible young stegosaurs were toe-walkers.

"This could be possible as this is the ancestral condition and a posture of most dinosaurs, but the stegosaur could also have transitioned to heel-walking as it got older," Dr Xing said.

"A complete set of tracks of these tiny footprints would provide us with the answer to this question, but unfortunately we only have a single footprint."

Finding the tiny tracks on crowded track sites will be challenging for the researchers.

"The footprints made by tiny armoured dinosaur are much rarer than those formed by other groups of dinosaurs," Associate Professor Xing said.

"Now that our study has identified nine different dinosaur track sites from this locality, we will look even closer to see if we can find more of these tiny tracks."

While Black, Hispanic, Latino, Indigenous, Asian and Pacific Islander people are more likely to die of COVID-19 than white people nationwide, a recent study from Oregon State University found the risk was even greater for racial and ethnic minority groups living in rural areas compared with urban areas.

To address the disparities, researchers say the health care response to COVID-19, including the vaccine rollout, needs to allocate additional resources to rural areas that have been hardest hit, especially those where minority populations are concentrated.

Earlier studies throughout the U.S. have shown that social determinants of health like poverty, access to reliable health care, chronic health conditions and type of occupation contribute to increased risk of COVID-19 infection and fatality for racial and ethnic minorities.

But living in a rural area on top of being a member of a racial minority group acts as a "double whammy," said Kwadwo Boakye, co-author on the study and a doctoral student focusing on epidemiology in OSU's College of Public Health and Human Sciences.

"It would not be ideal to say that 'rural versus urban' is a standalone thing. It has to be intertwined with the racial and ethnic disparity as well," to account for the disparate risk levels, Boakye said.

The study, published in the Journal of Racial and Ethnic Health Disparities, examined case fatality ratios during the period of Jan. 1 through Dec. 18, 2020. Researchers found that in that time, people living in "mostly rural" and "completely rural" counties who contracted COVID-19 were 15-26% and 15-24%, respectively, more likely to die from it than people in "mostly urban" counties who contracted the virus.

When researchers broke the results down by race, they found that the more rural a county was, as determined by census data, the higher the case-fatality ratio was for minority groups, especially for Black, Hispanic and Latino people. American Indian and Asian/Pacific Islander people also saw an increased case-fatality ratio in more rural counties.

In rural areas around the country, researchers noted that counties with larger percentages of Black, Hispanic/Latino and Asian/Pacific Islander people had clusters of higher COVID-19 case fatality.

"Generally, minorities are on the lower end of the spectrum for socioeconomic status. This may result in a need for them to work in occupations where they're in contact with a lot of other people, which puts them in more circumstances that are more prone to the spread of the virus," Boakye said.

In rural areas, most blue collar jobs are in agriculture, which means workers can't work from the safety of home during a pandemic, he said.

This study highlighted the impact that socioeconomic disparities and structural racism have had on health outcomes for racial and ethnic minorities over the decades, Boakye said.

"We are seeing with the COVID pandemic that minorities are at a larger risk of getting the disease, and also have a higher risk of mortality from the disease compared to other ethnic groups," he said.

"Compare living in a rural area, where you don't have a state-of-the-art medical facility with plenty of ventilators, to someone who is living in the city, who has access to all those facilities. We need health care facilities in these rural areas," Boakye said. "Policies should prioritize rural health and the adequate distribution of health resources to meet the needs of the minority populations, especially the distribution of COVID-19 vaccinations."

The researchers added that they were limited by the census data available; if they had been able to parse the numbers on an individual level, rather than aggregate, they could have obtained more specific results.

Prime editing (PE), a "search-and-replace" CRISPR-based genome editing technique, has great potential for gene therapy and agriculture. It can introduce desired base conversions, deletions, insertions, and combination edits into target genomic sites. Prime editors have been successfully applied in animals and plants, but their off-target effects, which can be a major hindrance to real-life application, have not been thoroughly evaluated until now.

Prof. GAO Caixia from the Institute of Genetics and Developmental Biology (IGDB) of the Chinese Academy of Sciences (CAS) and her research team recently performed a comprehensive and genome-wide analysis of the off-target effects of PEs in rice plants.

Off-target effects are in principle of two types: guide RNA (gRNA)-dependent and gRNA-independent. The first result from similarities between target and off-target sequences and the second from the activity of CRISPR-based tools, such as deaminase, at non-target positions in the genome.

The researchers first measured editing frequencies using pegRNAs with primer binding sites (PBSs) or spacers containing mismatches of the chosen target sequence, and found that mismatches located in seed sequence regions of the spacer (near the PAM) and near the nicking site of nCas9 (H840A) at the PBS greatly reduced the frequency of PE implying high editing specificity. They also evaluated the frequencies of editing by 12 pegRNAs at 179 endogenous off-target sites containing mismatches, and confirmed that editing rates were extremely low (0.00%~0.23%). Thus, designing pegRNAs with homology to fewer off-target sites is necessary.

The gRNA-independent effects induced by ectopic expression of functional elements in the CRISPR-based tools (which have been detected with some base editors) are not predictable by in silico methods. Gao et al. therefore used whole-genome sequencing to investigate whether ectopic expression of the prime editors induced undesired edits at the genome-wide level. They delivered PE constructs with or without pegRNA expression cassettes into rice calli via Agrobacterium-mediated transformation and obtained regenerated T0 plants (the PE group). They found the number of single nucleotide variants and indels (small insertions/deletions) in the PE group was not significantly higher than in the control group (expressing Cas9 nickase).

Moreover, mutation type analysis and mutation distribution analysis further demonstrated that the PE and control groups did not differ significantly. This result indicated that the PE system did not induce significant numbers of genome-wide pegRNA-independent off-target edits in plants.

Since M-MLV RT is a core element of the PE system, it seemed possible that overexpressing M-MLV RT might interfere with natural reverse transcription mechanisms in the cell. The researchers therefore evaluated the activities of retrotransposons and telomerase by analyzing the number of copies of the OsTos17 retrotransposon and the fidelity of telomeres, and found no effect of M-MLV reverse transcriptase on either parameter. They also evaluated the possibility that over-expression of RT might increase the risk of random reverse transcription of mRNAs and insertion of the products into the rice genome. Hence, they looked for pegRNA and mRNA insertions but detected no such events, further indicating that the M-MLV reverse transcriptase in PEs does not have nonspecific effects in plant cells. In summary, a systematic assessment demonstrated that prime editors are highly specific in plants.

It is an old-standing theory in evolutionary ecology: animal species on islands have the tendency to become either giants or dwarfs in comparison to mainland relatives. Since its formulation in the 1960s, however, the 'island rule' has been severely debated by scientists. In a new publication in Nature Ecology and Evolution on April 15, researchers solved this debate by analysing thousands of vertebrate species. They show that the island rule effects are widespread in mammals, birds and reptiles, but less evident in amphibians.

Dwarf hippos and elephants in the Mediterranean islands are examples of large species who exhibited dwarfism. On the other hand, small mainland species may have evolved into giants after colonizing islands, giving rise to such oddities as the St Kilda field mouse (twice the size of its mainland ancestor), the infamous dodo of Mauritius (a giant pigeon), and the Komodo dragon.

In 1973, Leigh van Valen was the first that formulated the theory, based on the study by mammologist J. Bristol Foster in 1964, that animal species follow an evolutionary pattern when it comes to their body sizes. Species on islands have the tendency to become either giants or dwarfs in comparison to mainland relatives. "Species are limited to the environment on an island. The level of threat from predatory animals is much lower or non-existent", says Ana Benítez-Lopez, who carried out the research at Radboud University, now researcher at Doñana Biological Station (EBD-CSIC, Spain). "But also limited resources are available." However, until now, many studies showed conflicting results which led to severe debate about this theory: is it really a pattern, or just an evolutionary coincidence?

Island rule confirmed

The team of scientists at Radboud University, Doñana Biological Station, National Museum of Natural Sciences and Imperial College London has revisited the island rule, aiming to solve this debate by performing a meta-analysis of over a thousand vertebrate species. They show that island rule effects are widespread in mammals, birds and reptiles, but less evident in amphibians, which mostly tend towards gigantism. The study also indicates that the magnitude of insular dwarfism and gigantism is more pronounced in smaller, more remote islands for mammals and reptiles.

Size is context-dependent

They also found an effect of climate and seasonality on the island rule. Small mammal and bird species grew larger and large species stayed the same size to conserve heat in colder, harsher insular environments. Furthermore, when seasons are present, availability of resources become less predictable for reptiles, leading smaller reptile species to become larger. Benítez-López: "Using a wealth of data from museum and live specimens, we were able to rigorously demonstrate for the first time that insular gigantism and dwarfism across vertebrates is a generalized pattern and not just an evolutionary coincidence."

A past COVID-19 infection does not completely protect against reinfection in young people, according to an observational study of more than 3,000 healthy members of the US Marines Corps most of whom were aged 18-20 years, published in The Lancet Respiratory Medicine journal.

The authors say that despite previous infection and the presence of antibodies, vaccination is still necessary to boost immune responses, prevent reinfection, reduce transmission, and that young people should take up the vaccine wherever possible.

In the study, between May and November 2020, around 10% (19 out of 189) of participants who were previously infected with SARS-CoV-2 (seropositive) became reinfected, compared with new infections in 50% (1,079 out of 2,247) of participants who had not previously been infected (seronegative).

Although the study was in young, fit, mostly male Marine recruits, the authors believe that the risk of reinfection found in their study will apply to many young people, but that the exact rates of reinfections will not be applicable elsewhere (owing to the crowded living conditions on a military base and close personal contact required for basic training likely contributing to a higher overall infection rate than seen elsewhere). For example, a study of 4 million people in Denmark also found that the risk of infection was five times higher in people who had not before had COVID-19, but they found that only 0.65% of people who had COVID-19 during Denmark's first wave tested positive again during the second wave, compared with 3.3% of people who tested positive after initially being negative [1]. In addition, a preprint study including British healthcare workers found that those who had been not previously infected had a five times higher risk of being reinfected than people who had a past infection [2].

Professor Stuart Sealfon, of Icahn School of Medicine at Mount Sinai, USA, and senior author of the study, says: "As vaccine roll outs continue to gain momentum it is important to remember that, despite a prior COVID-19 infection, young people can catch the virus again and may still transmit it to others. Immunity is not guaranteed by past infection, and vaccinations that provide additional protection are still needed for those who have had COVID-19." [3]

In the study, US Marine Corps recruits completed an unsupervised quarantine at home for two weeks before entering a Marine-supervised quarantine facility for another two weeks. They received antibody tests to establish whether any of the recruits were seropositive (they had previously been infected with SARS-CoV-2 and had antibodies). They were also tested for new SARS-CoV-2 infection at baseline then weeks one and two of the quarantine, and completed a questionnaire including demographic information, risk factors, medical history, and COVID-19 symptoms. Participants were excluded from the study if they tested positive for COVID-19 via PCR test during their supervised quarantine. After quarantine, recruits who did not have COVID-19 entered basic training and were tested for new SARS-CoV-2 infection by PCR tests every two weeks, for six weeks and completed follow up questionnaires about any COVID-19 symptoms.

Recruits who tested positive for a new second COVID-19 infection during the study were isolated and the study team followed up with additional testing. Levels of neutralising antibodies were also taken from subsequently infected seropositive and selected seropositive participants who were not reinfected during the study period.

Of the 2,346 Marines followed long enough for this analysis of reinfection rate, 189 were seropositive and 2,247 were seronegative at the start of the study. Across both groups of recruits, there were 1,098 (45%) new infections during the study. Among the seropositive participants, 19 (10%) tested positive for a second infection during the study. Of the recruits who were seronegative, 1,079 (48%) became infected during the study.

To understand why these reinfections occurred, the authors studied the reinfected and not infected participants' antibody responses. They found that, among the seropositive group, participants who became reinfected had lower antibody levels against the SARS-CoV-2 virus than those who did not become reinfected. In addition, in the seropositive group, neutralising antibodies were less common (neutralising antibodies were detected in 45 (83%) of 54 uninfected, and in six (32%) of 19 reinfected participants during the six weeks of observation).

Comparing new infections between seropositive and seronegative participants, the authors found that viral load (the amount of measurable SARS-CoV-2 virus) in reinfected seropositive recruits was on average only 10 times lower than in infected seronegative participants, which could mean that some reinfected individuals could still have a capacity to transmit infection, but the authors note that this will need further investigation.

In the study, most new COVID-19 cases were asymptomatic - 84% (16 out of 19 participants) in the seropositive group vs 68% (732 out of 1,079 participants) in the seronegative group - or had mild symptoms, and none were hospitalised.

Lt. Dawn Weir, of the Navy Medical Research Centre, USA, says: "Our study shows that some individuals with lower levels of neutralizing antibodies were reinfected, indicating that it is possible that previously infected and recovered people are susceptible to new SARS-CoV-2 infection at a later time. These reinfections may be asymptomatic, as observed in the majority of our participants. This is an important consideration for maintaining U.S. military operational readiness, such as preventing future COVID-19 outbreaks among Marine units or aboard Navy ships. The takeaway message for all young people, including our military service members, is clear - immunity resulting from natural infection is not guaranteed; you still need to be vaccinated even if you have had COVID-19 and recovered." [3]

The authors note some limitations to their study, including that it likely underestimates the risk of reinfection in previously infected individuals because it does not account for people with very low antibody levels following their past infection (in the study there were an unknown number of people in the seronegative group who had previously been infected but who did not have detectable levels of antibodies in their baseline antibody level test).

In the study there was a higher than usual drop-out rate of participants (a total of 566 participants - 34 recruits in the baseline seropositive group and 532 recruits in the baseline seronegative group - who began basic training and did not report for follow up two-weeks later). The study team were not told why any recruit did not return for follow up, but say that this could be a combination of individuals dropping out of the study, those who are transferred off the base for medical reasons, or who were separated from the US Marine Corps.

Lastly, the authors were unable to determine how seropositive recruits contracted their previous SARS-CoV-2 infection and confirm it by PCR test or determine how severe it was and what symptoms they had. They say they also could have missed detectable infections that occurred between the PCR testing every 2 weeks during the study.

Writing in a linked comment, María Velasco of Hospital Universitario Fundación Alcorcón, Spain, said: "This study was conducted in a closed setting but provides some interesting insights regarding the risk of subsequent SARS-CoV-2 infection in the general population or other settings. First, the rate of new SARS-CoV-2 PCR positive results is about 80% lower among seropositive individuals. These data confirm that seropositive individuals have a significant albeit limited protection for new infections [...] Second, the rate of new SARS-CoV-2 PCR detection among seropositive Marines cases is not negligible (1·1 cases per person-year), even in the young and healthy population. Globally, these results indicate that COVID-19 does not provide an almost universal and long-lasting protective immunity such as measles."

She continued: "Efforts must be made to reduce the risk of SARS-CoV-2 transmission from young oligosymptomatic individuals. Results from Letizia et al. suggest that even young individuals with a previous SARS-CoV-2 infection should also be a target of vaccination to avoid a poorly noticed source of transmission."

A number of SARS-CoV-2 variants have emerged from immunocompromised hosts, research has identified. It is thought that variants of concern - including B.1.1.7, a variant first identified in Kent - were a result of long-term infection in people with a weakened immune system.

Persistent infections in immunocompromised people could cause the virus to mutate more frequently because the person's immune system cannot clear the virus as quickly as the immune system of a healthy person.

Authors Professor Wendy Barclay, Dr Thomas Peacock, Professor Julian Hiscox and Rebekah Penrice-Randal explain the importance of monitoring genetic changes in SARS-CoV-2 for future control of the virus: "As more and more variants appear, we are getting a better picture of their shared similarities and differences and can better predict what other new variants will look like. Putting all this information together will also help us design booster vaccines that protect against as many variants as possible or design targeted diagnostics" they said.

Their review discusses where mutations have occurred, what part of the virus they affect and how the resulting variants could impact vaccination efforts. According to the authors, mutations in SARS-CoV-2 are expected, as the virus is adapting to humans. "Sequencing of human seasonal coronaviruses has not been done on a scale like SARS-CoV-2, particularly when they would have initially spread into humans. SARS-CoV-2 is at the start of its journey in humans whereas other human coronaviruses have been around, in some cases, for many decades" they said.

Variants with the same or similar mutations have emerged independently in different countries: "SARS-CoV-2 is probably still finding its way in humans in terms of optimal infection and transmission. The scale of the outbreak and the massive sequencing efforts will identify concurrent mutations; basically, the virus is undergoing the same types of selection pressures wherever you are in the world, and the outbreak was all seeded by the same original virus," explained the authors.

Mutations of particular interest include those in the spike protein. This protein allows the virus to enter host cells and is the main target of the immune system, including immunity generated by all current SARS-CoV-2 vaccines.

Mutations in the gene that codes for spike could change the shape of the protein, allowing it to no longer be recognised by the immune system. Because this protein is so important for SARS-CoV-2 entry, favourable mutations are more likely to succeed and create new, dominant variants of the virus.

Changes that give the virus an advantage can quickly become dominant. For example, one mutation, named D614G, was found in 80% of SARS-CoV-2 viruses sequenced just four months after it was first detected. Now, viruses without the D614G mutation are only commonly seen in parts of Africa.

Another mutation, N501Y, is found in the SARS-CoV-2 variant B.1.1.7. This mutation is believed to be the result of infection of an immunocompromised individual and may contribute to the virus being more contagious. Infections with this variant have a higher fatality rate. In the UK, B.1.1.7 became the dominant variant within three months and is now responsible for over 90% of infections there.

Significant spike protein mutations discussed in the review include:

D614G:

In February 2020, a mutation was detected in the spike protein of SARS-CoV-2 and named D614G. This mutation was found to makes SARS-CoV-2 more infectious, however does not make the virus more harmful. This increase in infectivity led to a significant fitness advantage and within four months, 80% of SARS-CoV-2 viruses sequenced around the world were found to have the mutation. Now, only parts of Africa have circulating viruses without the D614G mutation.

Despite initial concerns, D614G does not have an effect on vaccine efficiency and in some cases, viruses with the D614G mutation are more readily cleared by antibodies against SARS-CoV-2.

Y435F:

In mid-2020, reports of mink becoming infected by humans became frequent. In mink, the spike protein of the virus commonly developed two mutations called Y435F and N501T. These mutations allow for stronger binding of the virus to human receptor cells. Viruses with these mutations were found in a cluster of human infections in Denmark, believed to have originated from mink. Concerningly, this variant was able to infect people who had previously been infected with SARS-CoV-2 and were thought to have some immunity to the virus. As a result, 17 million mink were culled.

The mutation Y435F has also been reported to have developed in an immunocompromised person, possibly as a result of chronic infection with the virus allowing it to adapt.

N501Y:

In December 2020, a highly transmissible variant of the virus was isolated in Kent, UK. This variant, named B.1.1.7, contained a mutation in the spike protein called N501Y. Not only does this mutation make the virus more contagious, but it was also found to have a higher fatality rate. In the UK, B.1.1.7 is now the dominant variant, and is responsible for over 90% of infections.

The mutation N501Y has been found to have little effect on immunity from both vaccines and previous infections.

E484K:

The spike protein mutation E484K has emerged in recent months, once in South Africa and at least twice in Brazil. Variants with the mutation of E484K are able to evade the immune system of both vaccinated and previously infected individuals.

It is thought that this mutation was driven by high levels of population immunity, which drove mutations in the spike protein to evade the immune system. In Brazil, there have been several reports of healthcare workers and other people with antibodies against SARS-CoV-2 being reinfected with variants with the E484K mutant, raising concerns about vaccine protection against this variant.

The review also examines mutations which make changes to other parts of the virus, such as ORF8, an accessory protein that is thought to supress the host immune system. Viruses with a deletion in the gene that encodes for ORF8 has been found to cause less severe clinical disease.

The authors of the review have called for increased global efforts to monitor SARS-CoV-2 mutations. Currently the United Kingdom and Denmark perform disproportionately high sequencing of the SARS-CoV-2 genome. Regular monitoring of the virus allows early identification of emerging variants and allows researchers to identify the associated mutations.

"Although the genomic surveillance in Europe and the USA is fairly strong it is becoming clear there are large areas of the world that we simply have no idea what variants are circulating. These are starting to appear in Europe as imports or community outbreaks. Better surveillance across a broader range of countries would allow us to better risk assess what the next stage of the pandemic might look like," said the authors. "If we want to monitor the ongoing emergence, spread, and import of potential vaccine escape mutants we have to continue this effort or risk further pandemic waves and vaccine failure. Furthermore, understanding the genomic epidemiology of the virus as early as possible will allow us to rapidly develop updated vaccine boosters."

Professor Alain Kohl, Deputy Editor-in-Chief of the Journal of General Virology said "The emergence of SARS-CoV-2 variants is one of the great challenges in the ongoing pandemic. This review article summarises our current knowledge and understanding of the evolution of the virus, as well as the consequences - for example in terms of vaccination. It is of great interest to anyone wishing to learn more about the history of this virus and what the future may hold."

The extreme summer drought of 2018 was a special situation for both nature and scientists. It was very hard on the forest. At the same time, it offered researchers from the Universities of Basel (Switzerland) and Würzburg (Germany) the opportunity to study the reaction of trees to this climatic phenomenon.

Research in the treetops

"The summer of 2018 was hotter and drier than in any other year since weather records began," says ecophysiologist Professor Bernhard Schuldt from the University of Wuerzburg. Together with Dr Matthias Arend and Professor Ansgar Kahmen from the University of Basel, he was significantly involved in the study, which is published in the scientific journal PNAS. "A unique opportunity arose for us to study the influence of extreme heat and drought on large and old trees."

Using a crane set up in the forest, the researchers examined ten randomly selected spruce trees near Basel. They were all over 100 years old and around 30 metres high. The seasonal fluctuations of the water balance were measured directly in the uppermost tree crown.

Low but continuous water loss

The researchers are particularly interested in the duration and intensity of the drought that causes the water-conducting system in the wood to collapse. Due to its shallow root system, spruce in particular is susceptible to drought stress.

"We were able to show that the trees eventually die because their water-conducting system collapses within a very short time after a long drought," says Professor Schuldt. This, he says, is due to the small but continuous loss of water that takes place via the surfaces of the needles despite the fact that the leaf pores are closed.

The realisation that trees in general, and spruce in particular, suffer from drought is not news. For research, however, it is important to understand the processes underlying tree death in detail. This is exactly what the scientists from Basel and Wuerzburg have achieved with the study. "Our results provide an important contribution to improve predictions of drought-induced tree mortality," explains Schuldt.

Death comes very suddenly

The new results prove how dangerous heat waves are for trees due to the high dryness of the atmosphere and the associated high evaporation. According to the findings, the trees' hydraulic system can collapse completely within a very short time during the drought. Until now, it was assumed that this happens gradually as soon as the water supply from the soil is interrupted and the internal water reservoir are empty.

The decisive factor here is that the dehydration of the plant tissue does not seem to be a continuous process, but rather takes place abruptly after a species-specific threshold value has been exceeded. The spruce trees were unable to recover from this. "Whether this applies to other tree species such as beech, which was also severely affected by the drought, still needs to be clarified," says Schuldt.

A new paper in the Review of Economic Studies indicates that disease can alter the social networks and economic growth of countries for generations, even after the disease itself is eradicated.

Social networks are an important determinant of a country's growth as they affect the diffusion of ideas and the rate of technological progress. But social networks also diffuse diseases that can rapidly spread and dampen growth.

As ideas and germs diffuse through the same human interactions, the network structure of a country ultimately depends on its epidemiological environment. In countries with low prevalence of infectious diseases, high diffusion networks are more likely to emerge as they are better suited to diffuse technology and foster growth. On the other hand, in countries characterized by high prevalence of infectious diseases, low diffusion networks are more likely to emerge as limited connectivity protects people from epidemics. This insight has become particularly pertinent as economists reflect on the long term economic impact of the COVID-19 pandemic.

Using a newly assembled dataset for 71 countries and a theoretical model where germs, networks and technology evolve endogenously, the researchers show that small initial differences in a nation's epidemiological environment can trigger large and persistent differences in network structure that, over time, give rise to substantially different levels of technological diffusion and economic output. Speci?cally, a one-standard-deviation change in social network structure can increase the growth of output per worker by up to 2% per year.

The researchers then conduct policy experiments in which they hold constant the level of disease in the economy and exogenously change several features of the network structure that determine the speed of diffusion. What is the effect of introducing higher diffusion network on growth? Interestingly, the answer depends on the initial prevalence of disease.

Their benchmark is the United States, which has very low disease prevalence (0.05 percent for communicable diseases). In this environment, they find high-diffusion networks have a strongly positive impact on economic growth. Doubling the number of highly mobile or connected individuals raises growth rates substantially. But in a high-disease environment (using Ghana's 18 percent prevalence), altering the social network to facilitate faster diffusion lowers national income. Doubling the number of highly connected people causes output to fall by 90 percent.

The paper shows that how networks a?ect economic growth depends on the disease environment. In low disease countries, high diffusion networks promote the dissemination of new ideas and enhance growth. However, in a place where disease is prevalent networks can also lead to epidemics and humanitarian crisis.

"Germs, networks and growth are deeply interconnected," said the paper's lead author, Alessandra Fogli. "Strong networks have allowed our global economy to grow at an unprecedented rate. But they have also made it more vulnerable to the diffusion of new diseases. As social networks adapt to the new epidemiological environment, the COVID-19 pandemic can have long term consequences on economic growth."

An estimated 334,000 COVID-19 cases are attributable to meatpacking plants, resulting in $11.2 billion in economic damage, according to a new study led by a researcher at the University of California, Davis. The study was published in the journal Food Policy.

It found that beef- and pork-processing plants more than doubled per capita infection rates in counties that had them. Chicken-processing plants increased transmission rates by 20 percent. The study looked specifically at large meatpacking plants generating more than 10 million pounds per month.

Conservative estimate

Researchers said both the economic impact and infection rate estimate is conservative. The study looked at infection rates within a county and did not account for cases that might have been contracted at a meatpacking plant but spread to other counties.

"Similarly, our study likely understates true economic losses," said lead author Tina Saitone, a livestock and rangeland economics cooperative extension specialist in the Department of Agricultural and Resource Economics at UC Davis.

The study looked at lost wages and mortality and did not include long-term health care costs, or costs for measures put in place to protect worker safety.

"While we did see an initial ramp up in cases attributable to meatpacking facilities, over time infection rates were the same per capita as counties without them, partly because meatpacking plants implemented a lot of protocols to protect employees," said Saitone.

Driving factors

A variety of factors can drive county-level COVID-19 transmission rates. Saitone said the research controlled for those potential drivers, such as the number of nursing homes or correctional facilities in a county. It also considered stay-at-home orders and other regulations, population density, demographics, economic factors and health characteristics. The study looked at infections within 150 days after the first documented COVID-19 case in each county.

Essential industry

Increased COVID-19 transmission rates have prompted some critics to call for a smaller, more geographically dispersed industry to make it less susceptible to a pandemic and massive disruptions in the food supply chain. Researchers caution that such a move would come at a price, adding costs to a system designed to eliminate them and ultimately increasing food prices. Economists instead suggest research and investigation into the automation and technological innovations that made the poultry segment of the industry more resilient to the COVID-19 pandemic.

Study co-authors include K. Aleks Schaefer with Michigan State University and Daniel Scheitrum with the University of Arizona.

Philadelphia, April 15, 2021 - A new study shows that markers of fear recall differ between men and women, but in a hormone-dependent manner.

Aberrant fear-memory processing in the brain is thought to underlie anxiety disorders, which affect hundreds of millions of people worldwide. The neurobiological mechanisms underlying these disorders remain poorly understood, but recent studies suggest that neural oscillations in the prefrontal cortex can reflect the strength of fear recall activity, providing a physiological measure.

Women suffer from anxiety disorders at twice the rate of men and indeed the literature shows that there are sex differences in fear recall behaviors, but this area of study has not been extended to neural oscillations. Additional studies suggest a modulatory role for the female sex hormone estradiol (E2) for fear recall and extinction recall.

The new study led by Ursula Stockhorst, PhD, at the University of Osnabrück, Germany, specifically shows that peripheral and brain markers of fear recall differ in a hormone-dependent manner between men and women.

The work appears in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, published by Elsevier.

Cameron Carter, MD, Editor of Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, said of the work: "This study sheds light on the well-known differences between men and women in their vulnerability to anxiety disorders and shows that aspects of fear learning and extinction that contribute to vulnerability in women are related to differences in estrogen levels."

For the study, first author and PhD student Philipp Bierwirth, MSc, and colleagues examined 20 men, 20 women using oral hormonal contraceptives (OC) and 20 free-cycling women during their mid-cycle (MC). Women taking OC have suppressed and thus low endogenous E2 levels, whereas free-cycling MC women have higher levels of E2.

Participants underwent a fear-conditioning paradigm in which two of four photographs of neutral male faces were paired with a loud burst of white noise. Following the conditioning, the subjects underwent fear extinction, in which two photographs - only one of which had been paired with the noise - were again presented, but this time with no noise stimulus. The next day, subjects were shown all four photographs again, including the two that had been presented in the extinction phase and thus ready for extinction recall, and two of them without previous extinction - thus subject to fear recall. During all presentations, the researchers measured skin conductance responses (SCR), a peripheral readout of fear expression, and brain oscillations measured by electroencephalography.

Mr. Bierwirth said: "We found stronger peripheral fear expression (via SCR) during fear recall and extinction recall under low-E2 conditions, that is, in men and in OC women, compared to mid-cycle women with higher E2 levels. Most importantly, we also observed enhanced theta oscillations in the medial prefrontal cortex and especially in the dorsal anterior cingulate cortex (dACC), in men and OC women compared to MC women."

Importantly, the authors also point out that subjects were examined during their natural E2 status. They were not randomized to experimentally manipulated estrogen levels and so causal inferences about estrogen cannot be drawn.

Fear recall-related dACC theta oscillations were attenuated in women with higher E2 levels, which, importantly, supports previous findings suggesting a protective role for E2 against fear overexpression during the recall of fear and extinction memories. The data demonstrate that peripheral and brain oscillatory correlates of fear memory recall do not differ between the sexes per se but vary with E2 status, even among women.

PITTSBURGH, April 15, 2021 - Oncologists faced with treating older women with breast cancer often must decide if the treatment may be more detrimental than the cancer. A study published today in JAMA Network Open by researchers at UPMC Hillman Cancer Center and the University of Pittsburgh School of Medicine sheds new light on this choice and suggests the rate of cancer recurrence or survival may be no different in treated vs. untreated elderly patients diagnosed in the early stages of the cancer diagnosed most commonly in women.

"As a breast surgeon, I want to give my patients the best chance of survival with the best quality of life," said senior author Priscilla McAuliffe, M.D., Ph.D., surgical oncologist at UPMC Hillman Cancer Center and attending surgeon in the Department of Surgery at Pitt. "However, we have found that overtreatment of early-stage breast cancer in older patients may actually cause harm while not improving recurrence or survival rates."

Despite guidelines recommending the de-escalation of treatment among older women with early-stage cancer, there has been no definitive study of this patient cohort, who often are excluded in clinical trials because of their age.

To determine whether patients were being overtreated, the researchers analyzed deidentified data from more than 3,000 women over the age of 70 who were diagnosed with ER-positive, HER2-negative breast cancer from 2010 to 2018. Age 70 was used because clinical trials in breast cancer don't often include women in this age category. The data, collected at 15 UPMC Hillman Cancer Center community and academic sites, were evaluated with the UPMC Network Cancer Registry, which tracks cancer patients using UPMC's electronic health record system.

The study looked at two procedures: sentinel lymph node biopsy (SLNB), which is a surgical procedure to remove the lymph nodes from the underarm to determine if the cancer has spread beyond the breast, and radiotherapy (RT), which is standard treatment after breast-conserving surgery, given in multiple doses to control or kill any residual tumor. Side effects including nerve pain, lymphedema and skin irritation can sometimes occur after these procedures, which may be more difficult for the older patient to overcome.

The researchers found that the number of SLNB and RT procedures among patients over age 70 remained high at 65.3% and 54.4% respectively. The rates of SLNB also steadily increased by 1% per year, while rates of RT declined by 3.4% per year over the study period.

Most importantly, they found that the rates of disease recurrence or survival remained the same, whether the carefully selected patients received SLNB or RT, or not--no matter their comorbidities or tumor grade.

"This study is an example of how we can use big data to deliver on the promise of precision medicine--getting the right treatment to the right patient at the right time," said Adrian Lee, Ph.D., investigator at the Women's Cancer Research Center at UPMC Hillman Cancer Center and Magee Womens Research Institute, and director of the UPMC/Pitt Institute of Precision Medicine. "Sometimes--as it happens to be in this case--that could mean deciding not to provide a certain treatment to ensure better care for the patient."

The American Society of Breast Surgeons has released its second list of specific tests or procedures that clinicians and patients should question as part of Choosing Wisely®, an initiative of the ABIM Foundation. Lee hopes this study will further validate that a de-escalation of treatment for certain breast cancers will not affect the quality of life or outcome for patients and that SLNB and RT can safely be omitted.

"Our study is unique in that we were able to look at very granular patient data, thanks to the size of our health system and the availability of electronic medical records, which makes the findings more robust than any other such study to date," said Neil Carleton, lead author and an M.D./Ph.D. student at the Pitt. "This is the result of an incredible collaborative of researchers, oncologists and clinical analytics experts."

This video features the investigators discussing their study.

Hafnium-based thin films, with a thickness of only a few nanometres, show an unconventional form of ferroelectricity. This allows the construction of nanometre-sized memories or logic devices. However, it was not clear how ferroelectricity could occur at this scale. A study that was led by scientists from the University of Groningen showed how atoms move in a hafnium-based capacitor: migrating oxygen atoms (or vacancies) are responsible for the observed switching and storage of charge. The results, which were published online by the journal Science on 15 April, point the way to new ferroelectric materials.

Ferroelectric materials exhibit spontaneous polarization, which can be reversed or switched using an electric field. It is used in non-volatile memories or the construction of logic devices. One drawback of these materials is that when the size of the crystals is reduced to below a certain limit, the ferroelectric properties are lost. However, some years ago, it was suggested that hafnium-based oxides could exhibit ferroelectricity at nanoscale dimensions.

Microscope

In 2018, a team led by Beatriz Noheda, Professor of Functional Nanomaterials at the University of Groningen, confirmed these special properties of hafnium oxides. 'However, we didn't know exactly how this ferroelectricity occurred,' she says. 'We knew that the mechanism in these hafnium-based thin membranes is different. As ferroelectric switching is something that occurs at an atomic scale, we decided to study how the atomic structure of this material responds to an electric field, both using the powerful x-ray source at the MAX-IV synchrotron in Lund and our formidable electron microscope in Groningen.'

The University houses a state-of-the-art electron microscope at the electron microscopy centre of the Zernike Institute for Advanced Materials, with which the group of Bart Kooi, co-author of the Science paper, successfully imaged the lightest atoms in the periodic table - hydrogen - for the first time in 2020. This is where first author Pavan Nukala comes in. He worked as a Marie Curie Research Fellow at the University of Groningen and had a background in electron microscopy and materials science, especially in these ferroelectric hafnium systems.

Oxygen

However, if the preparation of a sample for the imaging of atoms is tricky, then the need to apply an electric field across a device in situ increases the difficulty by several orders of magnitude. Luckily, at around the same time, Majid Ahmadi (a master of in situ experiments) joined Kooi's group. 'All of us were quite convinced that if there was one place where switching of hafnium could be visualized in situ at an atomic scale, it would be here at the ZIAM electron microscopy centre. It benefits from a unique combination of the right expertise in materials science, microscopy and infrastructure,' Noheda explains.

The proper protocols for building hafnium-based electron-transparent capacitors using focused ion beam facility were developed by Ahmadi and Nukala. 'We imaged the atomic lattice of hafnium-zirconium oxide between two electrodes, including the light oxygen atoms,' Nukala explains. 'People believed that oxygen atom displacement in hafnium gives rise to polarization. So, any microscopy would only make sense if oxygen could be imaged and we had the exact tool for that. Then we applied an external voltage to the capacitor and watched the atomic changes in real time.' Such an in situ experiment with direct imaging of oxygen atoms inside the electron microscope had never been done.

Migration

'A significant feature that we observed is that the oxygen atoms move,' explains Nukala. 'They are charged and migrate following the electric field between the electrodes through the hafnium layer. Such a reversible charge transport enables ferroelectricity.' Noheda adds: 'This was a big surprise.' There is indeed also a small shift in atomic positions at the picometre scale inside the unit cells but the overall effect of the oxygen migration from one side to the other side on the device response is much larger. This discovery paves the way for new materials that could be used for nanometre-sized storage and logic devices. 'Hafnium-based ferroelectric memories are already in production, even though the mechanism behind their behaviour was unknown,' says Nukala. 'We have now opened up the road towards a new generation of oxygen-conducting, silicon-compatible ferroelectric materials.'

Noheda, who is the director of CogniGron, the Groningen Cognitive Systems and Materials Center, which develops new materials for cognitive computing, can see interesting applications for the new type of ferroelectric materials. 'Oxygen migration is much slower than dipole switching. In memory systems that could emulate the short-term and the long-term memory of brain cells, material scientists currently try to make hybrid systems from different materials to combine these two mechanisms. 'We can now do it in the same material. And by controlling oxygen movement, we could create intermediate states, again, like you find in neurons.'

Defects

Nukala, who is now an Assistant Professor at the Indian Institute of Science, is also interested in exploring the piezoelectric or electromechanical properties of the material. 'All conventional ferroelectrics are also piezoelectric. What about these new non-toxic, silicon-friendly ferroelectrics? There is an opportunity here to explore their potential in microelectromechanical systems.'

In the end, the properties of this new material stem from imperfections. 'The oxygen can only travel because there are oxygen vacancies inside the crystal structure,' says Nukala. 'In fact, you could also describe what happens as a migration of these vacancies. These structural defects are the key to the ferroelectric behaviour and, in general, give materials novel properties.'

Fifty-five years ago, America's death toll from automobile crashes was sky-high. Nearly 50,000 people died every year from motor vehicle crashes, at a time when the nation's population was much smaller than today.

But with help from data generated by legions of researchers, the country's policymakers and industry made changes that brought the number killed and injured down dramatically.

Research led to changes in everything from road construction and driver's license rules, to hospital trauma care, to laws and social norms about wearing seatbelts and driving while drunk or using a cell phone.

Now, researchers at the University of Michigan and beyond hope the country can do the same thing for the nearly 40,000 deaths and tens of thousands of injuries that now result from firearms each year, including homicides, suicides and unintentional incidents.

Two new papers on ways to reduce firearm use by people who are a danger to themselves and others are among their recent contributions.

Back in the headlines

A spate of recent mass shooting incidents, and an announcement from the White House about new actions at the federal level, have brought the issue back into the spotlight amid the COVID-19 pandemic.

But the research effort is starting almost from scratch, because of a 25-year near-total hiatus on federal research funding for firearm-related studies due to political reasons.

A 2019 U-M Injury Prevention Center study found that on a per-death basis, funding for pediatric firearm research is 30 times lower than it would have to be to keep pace with research on other child health threats.

That's despite the fact that since 2017, more Americans have died each year from firearm injuries than from the effects of motor vehicle crashes. Another U-M study showed that the rate of firearm death has risen sharply since 2015.

Using some of the scarce federal research funding available in recent years, U-M injury prevention researchers have worked to produce evidence to inform policies that strike a balance between preventing harm and respecting Second Amendment rights.

"Firearm violence leads to more than 100 deaths per day across the country, and so in order for us to address this public health crisis, we need researchers to work together, generating new knowledge and advancing innovative solutions," says Rebecca Cunningham, M.D., U-M vice president for research and the William G. Barsan Collegiate Professor of Emergency Medicine at the U-M Medical School. "We are starting to see some momentum in terms of increased funding to support this important work, which hopefully will strengthen the pipeline of researchers who can devote their careers to studying firearm injury prevention and provide data and solutions toward decreasing injury and death."

Initial research efforts

U-M launched a Firearm Injury Prevention Research initiative in 2019 to build on that momentum, and overcome the lack of firearm-related research funding available from federal sources that fund most other biomedical and social research.

Michigan experts have joined with academics and health professionals across the country to share research data, and evaluate interventions based on past research through the Firearm Safety Among Children and Teens consortium, funded by the National Institutes of Health.

The FACTS consortium has done deep-dives into the state of research on firearm death and injury in children and adolescents, and laid out priorities for future research efforts.

Its members have already launched several studies, including one whose results were published this week.

It finds that Oregon's "red flag" law is indeed being used to remove firearms from people who are determined by a judge to be at extreme risk of committing violence against themselves or others, but that it's not often used for its other intended purpose, to prevent gun purchases by such individuals. The White House announcement called for more use of "red flag" laws, also called extreme risk protection orders (ERPOs) or gun violence restraining orders.

Cunningham and U-M President Mark Schlissel, M.D., Ph.D., recently hosted a virtual panel discussion of U-M faculty who are doing a wide range of research on firearm injury prevention.

Patrick Carter, M.D., director of the U-M Injury Prevention Center, and like Cunningham, an emergency medicine physician at Michigan Medicine, welcomes the news from the federal government.

"An exciting aspect of President Biden's announcement is the renewed focus on advancing the science of firearm injury prevention through federal research funding," he says. "Such research is crucial to developing a better understanding of the factors underlying this critical public health problem, as well as advancing evidence-based solutions that will reduce the number of Americans that die or are injured by firearms every year."

In addition to producing new research results, it's also important to turn research findings into useful tools for families and community leaders. That includes fact-based information about firearm safety for parents.

It also includes the entire kit to help primary care providers use the SaferTeens approach developed and tested by U-M. It screens young people for risk of violence and conducts a brief intervention to help them focus on reducing that risk.

A focus on firearm suicide risk

In addition to the recent spate of mass shootings, and a sharp uptick in gun sales, the pandemic's impact on the mental health and the economic state of many Americans also makes this a crucial time to study ways to reduce firearm-related death and injury due to suicidal actions.

In 2018, 52% of all suicides in Michigan involved a firearm, according to data in the newly released report from the Michigan Suicide Prevention Commission. Nearly all suicide attempts involving firearms result in a death, past research has shown.

John Greden, M.D., professor emeritus of psychiatry and neurosciences at U-M, serves on the commission. He is the founding director and immediate past director of the Frances and Kenneth Eisenberg and Family Depression Center, as well as past chair of the U-M Department of Psychiatry.

In its list of recommendations, the commission calls for more efforts to reduce suicide by firearm, including more awareness and training involving everyone from shooting sports clubs and gun shops to veterans' groups. It also calls for health care providers to routinely assess their patients' access to firearms and other lethal means, if the patient is at risk for suicide. The new report includes a list of research projects now under way at U-M specifically focused on suicide risk identification and reduction.

One group of patients with such a high risk includes those with depression, and those with bipolar disorder, a mental illness that involves sharp swings between manic periods and depressed periods.

That's what prompted U-M psychiatrist Melvin McInnis, M.D., and U-M Law School professor Carl Schneider, J.D., to write a recent paper that sets out a legal framework for people with depression and bipolar disorder to place themselves on an official list that would keep them from purchasing firearms.

"Bipolar and depressive disorders very often include suicidal thinking that may lead to suicide," says McInnis, who directs the Heinz C. Prechter Bipolar Research Program at the Eisenberg Family Depression Center. "When well individuals with these disorders live productive lives and have no wish to harm themselves or anyone. A powerful gun-violence prevention tool is a volunteer self-exclusion option for anyone for any reason to register with the Department of Justice and be placed on a list that would prevent them from purchasing guns or firearms."

The U-M Injury Prevention Center also recently held a Suicide Prevention Summit to share the latest results from suicide-related research, including research on firearm-based suicide. Recordings of the presentations are available online.

Among the topics discussed was an effort to reduce suicide by firearm among young people living in rural communities, who have an especially high risk. Working with community groups, U-M Department of Psychiatry and IPC researcher Cynthia Ewell-Foster, Ph.D., and colleagues are trying to encourage evidence-based safe firearm storage among families with children in rural northern Michigan.

Race as a risk factor

The other major issue brought to great public attention in the past year - the effects of systemic, long-term race-based discrimination on the health of people of color - also has importance for the firearm issue and research.

Firearms are the number-one cause of death for young black men, and firearm injury rates are more than three and a half times higher for Black children and teens than for whites.

Cunningham, Carter and their colleagues have studied the role of firearms in the lives of teens and young adults in Flint, Michigan for nearly a decade, through interactions begun in the emergency department. The SaferTeens program grew out of that work.

Now, they're testing an approach based on a mobile app that enables remote counseling for youth at risk of firearm violence through an effort called Project IntERact.

These projects, and more getting started around the country as research funding grows, are an important start. The increased availability of funding is also likely to draw more junior researchers and injury prevention students to the field of firearm injury, because the promise of a stable source of research funding is crucial to the choice of subject a researcher chooses for their career. That's also what happened 50 years ago with motor vehicle crash research.

"This is a complex problem, but it's not a more complex problem," than motor vehicle-related injuries and deaths, says Cunningham. "There is an awakening that we can really do more."