It’s possible that I shall make an ass of myself. But in that case one can always get out of it with a little dialectic. I have, of course, so worded my proposition as to be right either way (K.Marx, Letter to F.Engels on the Indian Mutiny)
Wednesday, September 14, 2022
IT'S CTHULHU
Scientists reveal the true identity of a Chinese octopus
As they were collecting cephalopod samples in Dongshan island in China’s Fujian Province, a team of researchers came across an interesting finding: a new-to-science species of octopus.
Actually, locals and fishermen have long been familiar with the species -but they kept mistaking it for a juvenile form of the common long-arm octopus (‘Octopus’ minor), whose trade is widespread throughout the country.
Only when a team of scientists from the Ocean University of China collected a batch of specimens misidentified by locals from Dongshan Seafood Market Pier as ‘O’. minor to study them, did it become apparent that this was in fact a separate, new species. That’s how it got its own name, Callistoctopus xiaohongxu, and a scientific description published in the open-access journal ZooKeys.
The scientific name xiaohongxu is a phonetic translation of the local Chinese name of this species in Zhangzhou, where it was collected. It is a reference to its smooth skin and reddish-brown colour, which are among its most distinctive features. At less than 40 g in its adult stage, C. xiaohongxu is considered a small to moderate-sized octopus.
The researchers also note that this is the first new species of the genus Callistoctopus to be found in the China Seas.
More than 130 different cephalopod species are recorded in Chinese waters. Тhe southeast waters of China, due to the influence of strong warm currents, provide ideal environmental conditions to generate abundant marine biodiversity, and the finding of C. xiaohongxu further confirms the high diversity of species in the southeast China sea, the researchers said.
Research article:
Zheng X, Xu C, Li J (2022) Morphological description and mitochondrial DNA-based phylogenetic placement of a new species of Callistoctopus Taki, 1964 (Cephalopoda, Octopodidae) from the southeast waters of China. ZooKeys 1121: 1-15. https://doi.org/10.3897/zookeys.1121.86264
A live individual of Callistoctopus xiaohongxu
CREDIT
Zheng et al.
CAPTION
A net-like web structure on Callistoctopus xiaohongxu
Morphological description and mitochondrial DNA-based phylogenetic placement of a new species of Callistoctopus Taki, 1964 (Cephalopoda, Octopodidae) from the southeast waters of China
ARTICLE PUBLICATION DATE
12-Sep-2022
Scientists say the best way to soothe a crying infant is by carrying them on a 5-minute walk
Most parents have experienced frustration when their infants cry excessively and refuse to sleep. Scientists have found that the best strategy to calm them down is by holding and walking with them for five minutes. This evidence-based soothing strategy is presented in a paper published September 13 in the journal Current Biology.
“Many parents suffer from babies’ nighttime crying,” says corresponding author Kumi Kuroda of the RIKEN Center for Brain Science in Japan. “That’s such a big issue, especially for inexperienced parents, that can lead to parental stress and even to infant maltreatment in a small number of cases,” she says.
Kuroda and her colleagues have been studying the transport response, an innate reaction seen in many altricial mammals—those whose young are immature and unable to care for themselves—such as mice, dogs, monkeys, and humans. They observed that when these animals pick up their infants and start walking, the bodies of their young tend to become docile and their heart rates slow. Kuroda’s team wanted to compare the effects of the transport response, the relaxed reaction while being carried, with other conditions such as motionless maternal holding or rocking and also examine if the effects persist with longer carrying in human infants.
The researchers compared 21 infants’ responses while under four conditions: being held by their walking mothers, held by their sitting mothers, lying in a still crib, or lying in a rocking cot. The team found that when the mother walked while carrying the baby, the crying infants calmed down and their heart rates slowed within 30 seconds. A similar calming effect occurred when the infants were placed in a rocking cot, but not when the mother held the baby while sitting or placed the baby in a still crib.
This suggests that holding a baby alone might be insufficient in soothing crying infants, contradicting the traditional assumption that maternal holding reduces infant distress. At the same time, movement has calming effects, likely activating a baby’s transport response. The effect was more evident when the holding and walking motions continued for five minutes. All crying babies in the study stopped crying, and nearly half of them fell asleep.
But when the mothers tried to put their sleepy babies to bed, more than one-third of the participants became alert again within 20 seconds. The team found that all babies produced physiological responses, including changes in heart rate, that can wake them up the second their bodies detach from their mothers. However, if the infants were asleep for a longer period before being laid down, they were less likely to awaken during the process, the team found.
“Even as a mother of four, I was very surprised to see the result. I thought baby awoke during a laydown is related to how they’re put on the bed, such as their posture, or the gentleness of the movement,” Kuroda says. “But our experiment did not support these general assumptions.” While the experiment involved only mothers, Kuroda expects the effects are likely to be similar in any caregiver.
Based on their findings, the team proposes a method for soothing and promoting sleep in crying infants. They recommend that parents hold crying infants and walk with them for five minutes, followed by sitting and holding infants for another five to eight minutes before putting them to bed. The protocol, unlike other popular sleep training approaches such as letting infants cry until they fall asleep themselves, aims to provide an immediate solution for infant crying. Whether it can improve infant sleep in the long-term requires further research, Kuroda says.
“For many, we intuitively parent and listen to other people’s advice on parenting without testing the methods with rigorous science. But we need science to understand a baby’s behaviors, because they’re much more complex and diverse than we thought,” Kuroda says.
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This research was supported by RIKEN Center for Brain Science and the Japan Society for the Promotion of Science.
Current Biology (@CurrentBiology), published by Cell Press, is a bimonthly journal that features papers across all areas of biology. Current Biologystrives to foster communication across fields of biology, both by publishing important findings of general interest and through highly accessible front matter for non-specialists. Visit http://www.cell.com/current-biology. To receive Cell Press media alerts, contact press@cell.com.
New research published in Current Biology on September 13 demonstrates the importance of carrying crying infants rather than simply holding them. Led by Kumi Kuroda at the RIKEN Center for Brain Science (CBS) in Japan, the study details how crying babies are physiologically affected by being held, carried, and laid down. The data yield a simple but cost-free and effective technique that increases the chance of getting a crying infant to calm down and sleep in bed.
Most parents know the occasional frustration and discomfort of dealing with a crying baby. For some, it’s a regular occurrence that affects the baby’s ability to sleep and stresses out the parents. What can you do in this situation? Kuroda and her team found a “Transport Response” in distressed mouse pups and human babies in which infants calm down when carried by their mothers. The response is a complex series of parallel biological processes that result in reduced crying and lower heart rates, which helps parents to transport the infants.
The new study used a baby ECG machine and video cameras to systematically compare changes in heartrate and behavior as mothers acted out activities that are commonly used to calm infants, including carrying, being pushed in a stroller, and holding while sitting. Data during these activities were recorded from babies that were crying, awake and calm, or sleeping. At each heartbeat, behavior was assessed as asleep, alert, or crying, and scored accordingly. This way the researchers could track changes in both behavior and physiology with sub-second precision.
The experiment led to a few important findings. First, as Kuroda explains, “walking for five minutes promoted sleep, but only for crying infants. Surprisingly, this effect was absent when babies were already calm beforehand.” Among the babies studied, all had stopped crying by the end of the five-minute walk and had reduced heart rates, and about half were asleep. Second, sitting and holding crying babies was not calming; heart rates tended to go up and crying persisted.
The heartbeat measure allowed the researchers to dissect the effect of each micro-activity as infants were handled. The researchers found that the babies were extremely sensitive to all movements by their mothers. For example, heartrates went up when mothers turned or when they stopped walking. The most significant event that disturbed the sleeping infants happened just when they became separated from their mothers.
Every mother has experienced the disappointment of having a finally sleeping baby wake up again after being put down. The researchers pinpointed the problem using the heartbeat data. “Although we did not predict it,” says Kuroda, “the key parameter for successful laydown of sleeping infants was the latency from sleep onset.” Babies often woke up if they were put down before they got about 8 minutes of sleep. Thus, based on the data, Kuroda recommends that when babies are crying too much and can’t sleep, mothers should carry them steadily for about 5 minutes with few abrupt movements, followed by about 8 minutes of sitting before laying them down for sleep.
Although this procedure does not address why some babies cry excessively and cannot sleep, it offers an immediate solution that can help parents of newborns. Additionally, the researchers recognize the usefulness of heartrate data in this age of wearable fitness devices. “We are developing a “baby-tech” wearable device with which parents can see the physiological states of their babies on their smartphoness in real-time,” says Kuroda. “Like science-based fitness training, we can do science-based parenting with these advances, and hopefully help babies to sleep and reduce parental stress caused by excessive infant crying.”
Reference: Ohmura et al. (2022) A method to soothe and promote sleep in crying infants utilizing the Transport Response. Curr Biol. doi: 10.1016/j.cub.2022.08.041
TORONTO, September 13, 2022 – More than two years after the start of the pandemic, adults still have difficulty recognizing people when their face is obscured by a mask, found a new study out of York University.
Researchers found repeated exposure of masked faces throughout the pandemic has made zero difference in adults’ ability to recognize these half-hidden faces.
“Neither time nor experience with masked faces changed or improved the face mask effect,” says York University Assistant Professor Erez Freud of Faculty of Health, the study’s senior author. “This tells us that the adult brain doesn’t not seem to have the ability to change how it processes faces, even when presented with masked faces over an extended period of time.”
The ongoing pandemic provided an unprecedented opportunity for the researchers to examine the plasticity of the mature face processing system.
The researchers repeatedly tested more than 2,000 adults by show them a series of faces, upright and inverted, with and without masks. Different groups of adults were tested at six different points in time during the pandemic. In addition, the researchers tested the same group near the start of the pandemic and 12-months later. In both the cross-sectional and longitudinal studies, adults showed absolutely no increase in their ability to recognize masked faces.
Previous research showed that adults’ facial recognition abilities decreased by about 15 per cent when the person wore a mask using the Cambridge Face Memory Test (CFMT), which as considered as the standard to tap face recognition abilities. Face masks also interfere with how unmasked faces are processed – which is normally made in a holistic manner, rather than by the individual parts of the face. This new study not only used the CFMT, but also the Glasgow Face Match Test, an additional measure of face perception, to determine if anything changed since the last study.
“This shows that face processing in humans, at least in adults, is rigid even after prolonged real-life exposure to partially covered faces,” says Freud.
Face sensitivity first shows up in newborns who exhibit a preference for faces or things that look similar to a face, and especially to familiar faces. In contrast to the mature face processing system, repeated exposure to faces as a child plays an important role in refining the face processing system, which continues to develop until the end of puberty.
Freud says it would be interesting to see if children’s ability to recognize masked faces changes over time with exposure, and whether the pandemic has interfered with their normal ability to recognize faces.
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Media Contact: Gloria Suhasini, York University Media Relations, 647-463-4354, suhasini@yorku.ca
CLEVELAND–Older people who were infected with COVID-19 show a substantially higher risk—as much as 50% to 80% higher than a control group—of developing Alzheimer’s disease within a year, according to a study of more than 6 million patients 65 and older.
In a study published today in the Journal of Alzheimer’s Disease, researchers report that people 65 and older who contracted COVID-19 were more prone to developing Alzheimer’s disease in the year following their COVID diagnosis. And the highest risk was observed in women at least 85 years old.
The findings showed that the risk for developing Alzheimer’s disease in older people nearly doubled (0.35% to 0.68%) over a one-year period following infection with COVID. The researchers say it is unclear whether COVID-19 triggers new development of Alzheimer’s disease or accelerates its emergence.
“The factors that play into the development of Alzheimer’s disease have been poorly understood, but two pieces considered important are prior infections, especially viral infections, and inflammation,” said Pamela Davis, Distinguished University Professor and The Arline H. and Curtis F. Garvin Research Professor at the Case Western Reserve School of Medicine, the study’s coauthor.
“Since infection with SARS-CoV2 has been associated with central nervous system abnormalities including inflammation, we wanted to test whether, even in the short term, COVID could lead to increased diagnoses,” she said.
The research team analyzed the anonymous electronic health records of 6.2 million adults 65 and older in the United States who received medical treatment between February 2020 and May 2021 and had no prior diagnosis of Alzheimer’s disease.
They then divided this population two groups: one composed of people who contracted COVID-19 during that period, and another with people who had no documented cases of COVID-19. More than 400,000 people were enrolled in the COVID study group, while 5.8 million were in the non-infected group.
“If this increase in new diagnoses of Alzheimer’s disease is sustained, the wave of patients with a disease currently without a cure will be substantial, and could further strain our long-term care resources,” Davis said. “Alzheimer’s disease is a serious and challenging disease, and we thought we had turned some of the tide on it by reducing general risk factors such as hypertension, heart disease, obesity and a sedentary lifestyle. Now, so many people in the U.S. have had COVID and the long-term consequences of COVID are still emerging. It is important to continue to monitor the impact of this disease on future disability.”
Rong Xu, the study’s corresponding author, professor of Biomedical Informatics at the School of Medicine and director of the Center for AI in Drug Discovery, said the team plans to continue studying the effects of COVID-19 on Alzheimer’s disease and other neurodegenerative disorders—especially which subpopulations may be more vulnerable—and the potential to repurpose FDA-approved drugs to treat COVID’s long-term effects.
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AUSTIN, Texas — When women and men raise their voices together in the workplace, managers are more likely to support gender equity issues, such as equal pay for equal work. That’s the finding of a new paper from a researcher at The University of Texas at Austin.
In a recent study, Insiya Hussain, an assistant professor of management at UT Austin’s McCombs School of Business, surveyed 3,234 participants during three separate studies.
With colleagues Subra Tangirala of the University of Maryland and Elad Sherf of the University of North Carolina at Chapel Hill, she asked each group a different set of questions about a range of gender equity proposals, from training women in how to negotiate for higher pay to ensuring that women formed at least 50% of the candidates for leadership positions.
In each of the three studies, participants — including those in managerial roles — reacted more favorably overall to mixed-gender coalitions than to women-only or men-only advocates. This is because:
Mixed-gender coalitions (owing to the participation of men) were able to signal that gender equity is an important issue for the organization.
Additionally, mixed-gender coalitions (owing to the participation of women) were able to signal that they had the right to speak up about gender equity issues.
“This research addresses how best to form an advocacy group to raise these issues, if you want to get results,” Hussain said.
Managers see women as legitimate messengers, Hussain said, because they have personal interests in an issue. But adding men makes the message itself appear more legitimate by indicating that it matters to a wider range of stakeholders.
“When only women advocate for gender equity, it can come across as a niche concern,” she said. “When men speak up about it, they can be seen as lacking the right to protest an issue that doesn’t personally concern them. It’s really when you bring women and men together as advocates that you circumvent both concerns.”
The researchers noted that the effect was limited to women’s issues. When managers were asked to take actions on nongender equity issues, such as training to improve customer service skills, mixed-gender coalitions showed no advantage.
But the lesson might apply beyond women’s issues. Other kinds of socially charged workplace concerns, such as racial justice, could potentially benefit from demographically diverse coalitions. For instance, if a group is trying to advance racial equity in the workplace, a coalition of white and Black employees might be better able to signal both coalition legitimacy and issue legitimacy.
Although women have yet to reach equality in many workplaces, the researchers were encouraged at how seriously the participants took women’s proposals. On the scale from 0 to 7, their levels of support ranged from 4.47 to 5.43.
“If we had run this study 10 or 20 years ago, we might have uncovered much poorer attitudes toward gender equity in general,” Hussain said. “And as the workplace is always evolving, these findings may change 10 or 20 years from now, with more social progress. At least today, though, it helps to recruit men as allies. Gender equity advocacy is most effective when women and men work together.”
Signaling Legitimacy: Why Mixed-Gender Coalitions Outperform Single-Gender Coalitions in Advocating for Gender Equity
‘Years of life lost’ to unintentional drug overdose in adolescents spikes during pandemic
The first year of the COVID-19 pandemic saw a 113% increase in the “Years of Life Lost” among adolescents and young people in the United States due to unintentional drug overdose
COLUMBUS, Ohio – The first year of the COVID-19 pandemic saw a 113% increase in the “Years of Life Lost” among adolescents and young people in the United States due to unintentional drug overdose, according to researchers at The Ohio State University Wexner Medical Center and College of Medicine.
Study findings published online in the Journal of Adolescent Healthalso document the role of fentanyl in rising overdose rates.
Excess mortality was calculated in Years of Life Lost (YLL), which is the difference between the age at which a person dies and their expected remaining lifespan. In 2019, U.S. life expectancy at birth was 78.8 years, according to the Centers for Disease Control and Prevention (CDC).
“Mortality due to unintentional overdose in adolescents reached an all-time high in 2020,” said addiction medicine specialist Dr. O. Trent Hall, study corresponding author and an assistant professor of Psychiatry and Behavioral Health at Ohio State. “The majority of deaths involved fentanyl and other synthetic opioids. The trends depicted in this study signify the need for increased harm-reduction approaches and treatment of opioid use disorder in adolescents.”
The number of adolescent YLL to unintentional drug overdose in the United States more than doubled from 39,579 in 2019 to 84,179 in 2020 – an increase of 113% – after remaining relatively stable between 2016 and 2019. In 2020, the accumulated total of YLL to unintentional overdose surpassed that of cancer, said study first author Dr. Sarah Perou Hermans, clinical instructor in Ohio State’s Department of Internal Medicine.
Synthetic opioids – including primarily illicitly manufactured fentanyl – contributed to 81% of overdose deaths and 68,356 YLL, compared to 67% and 26,628 YLL in 2019. In addition, YLL to unintentional overdose during 2020 was higher for males (59,274) compared to females (24,905), Hermans said.
Researchers obtained data from the CDC’s Wide-Ranging Online Data for Epidemiologic Research mortality file for years 2016-2020 to investigate unintentional overdose in adolescents aged 10-19.
“Our findings contribute to an emerging body of research documenting adolescent overdose and the impact of fentanyl across communities and this vulnerable population,” Hermans said. “The death of a single adolescent to accidental drug overdose is unacceptable. We have sounded the alarm. Now it is time to start putting out the fire. We hope this study will spur public health officials into action. Our society has to prioritize these young lives.”
This study replicates and extends Hall’s earlier research, “Unintentional Drug Overdose Mortality in Years of Life Lost Among Adolescents and Young People in the US From 2015 to 2019,” published in JAMA Pediatrics in January. That study was the first to use YLL to assessed unintentional drug overdose mortality among adolescents and young people.
“Our study extends on this research by examining trends by year, as well as by gender, age and substances involved. This study then compared unintentional overdoses with other leading causes of adolescent death to further quantify the impact of these mortalities,” said Hermans.
For next steps, the research team intends to study overdose prevention, substance use treatment and harm reduction approaches to stop adolescents dying from overdose.
CHAPEL HILL, North Carolina -- Giving standard chemotherapy drugs in a specific sequence for some types of metastatic breast cancer can help reduce overall costs and improve the value of care while preserving quality of life, according to a study led by UNC Lineberger Comprehensive Cancer Center and UNC Gillings School of Global Public Health researchers.
The researchers developed three different computer models to predict how a hypothetical set of 10,000 patients with specific types of metastatic breast cancer would respond to different sequences and types of chemotherapy. For this study, the patient’s cancer was either no longer responding to hormone therapies (endocrine resistant) or was a type of the disease called triple-negative breast cancer.
Currently, there are many chemotherapy choices to treat metastatic breast cancer. Oncologists have some preferences of which drugs to use early in treatment, but there is little clear evidence on the best order in which to give the drugs. The researchers consulted oncologists and experts in the field to choose which chemotherapy drugs were preferred choices to include in the study.
Mimicking clinical practice, and based upon existing data, the researchers then assumed that if a person started treatment with one drug, they would change to a second-choice treatment after their cancer stopped responding to the first drug, or if the side effects weren’t tolerable. The purpose of the study was to test whether putting the drugs in one sequence compared to another could keep the patient on treatment for similar times while decreasing their side effect and/or cost burden.
“The cost of cancer drugs in the U.S. has rapidly increased, even for generics. As a society, we urgently need more strategies to reduce cancer drug costs without compromising outcomes, and our analysis provides quantifiable evidence to help providers choose lower priced, but equally effective sequences of drugs,” said Stephanie B. Wheeler, PhD, MPH, professor of health policy & management at UNC Gillings and associate director of community outreach and engagement at UNC Lineberger and corresponding author of the article. “More spending on cancer care does not necessarily confer greater health benefits.”
The costs calculated in this study were inclusive of medical and nonmedical costs borne by patients, including lost productivity. In this simulation, after two years, nearly all women would have completed the first three sets of treatment, but the cancer would cause the death of about one-third of the women. Productivity days lost due to sickness were similar across chemotherapy sequences, so most of the cost difference was due to drug savings. In the simulation, patients were placed in three groups, depending on what treatments they had already received for earlier episodes of breast cancer.
Outcomes in the three groups were:
For people who had not previously received the common chemotherapy drug categories, including a taxane (e.g., paclitaxel) or an anthracycline (e.g., capecitabine), treatment with paclitaxel then capecitabine followed by doxorubicin corresponded to the highest expected gains in quality of life and lowest costs.
For people who had previously received a taxane and an anthracycline drug, treatment with carboplatin, followed by capecitabine, followed by eribulin, corresponded to the highest expected gains in quality of life and lowest costs.
For people who had previously received a taxane but not an anthracycline, treatment sequences beginning with capecitabine or doxorubicin, followed by eribulin, were most cost-effective.
“The drugs we studied are already recommended and reimbursed for the treatment of metastatic breast cancer, but the optimal sequencing of them has been unclear, which has led to considerable variation in physician preference and practice. Our study suggests that treatment sequencing approaches that minimize costs early may improve the value of care,” Wheeler said. “The implications of this study are fairly straightforward for medical oncologists and those developing value-based clinical pathways to implement in practice now.”
"I hope our study will help expand the framework that we use to make these decisions from one where we just think about the biologic action of the drug to one where we also consider the bigger picture of what the treatment experience is like for the patient, including their financial burden, investment of time, and side effects,” said Katherine Reeder-Hayes, MD, MBA, MSc. “The most potent drug isn’t always the next best choice depending on what the patient values and wants to accomplish with their treatment.”
CREDIT
UNC Lineberger Comprehensive Cancer Cente
UNC Lineberger’s Katherine E. Reeder-Hayes, MD, MBA, MSc, section chief of breast oncology and associate professor of medicine at UNC School of Medicine and one of the study’s authors, said the treatment choices for metastatic breast cancer are constantly changing, and new options for targeted therapy have emerged even since this study was conducted. “Many oncologists and patients find that there aren’t any more targeted therapies that fit the cancer’s molecular profiles, so they are left with the choice of a number of chemotherapy drugs that may feel pretty similar or have an unclear balance of pros and cons.
“In that scenario, I hope our study will help expand the framework that we use to make these decisions from one where we just think about the biologic action of the drug to one where we also consider the bigger picture of what the treatment experience is like for the patient, including their financial burden, investment of time, and side effects,” Reeder-Hayes added. “The most potent drug isn’t always the next best choice depending on what the patient values and wants to accomplish with their treatment.”
Looking ahead, the researchers have developed a financial navigation program to further support patients in managing the out-of-pocket costs of their cancer care. This program has been effective and well received by patients, caregivers and providers. The team is currently scaling up the intervention in nine rural and non-rural oncology practices across North Carolina to understand how well it works in different care settings. Cancer patients who need financial support managing the cost of their cancer care are being recruited for this undertaking.
Authors and Disclosures
In addition to Wheeler and Reeder-Hayes, the other authors at UNC are Jason Rotter, PhD; Anagha Gogate, PhD; Sarah W. Drier, MPH; and Justin G. Trogdon, PhD. Donatus U. Ekwueme, PhD, MS and Temeika L. Fairley, PhD, are at the Centers for Disease Control and Prevention (CDC) in Atlanta. Gabrielle B. Rocque, MD, is at the University of Alabama at Birmingham.
The research was supported by the CDC through the Prevention Research Centers Program (5-U48-DP005017-04-01).
Wheeler and Reeder-Hayes are members of UNC Lineberger, which has received institutional research funding from Pfizer. Gogate reported employment and stock and other ownership interests in Bristol Myers Squibb/Celgen. Rocque reported consulting or an advisory role with Pfizer, Flatiron Health and Gilead Sciences and receiving research funding from Carevive Systems, Genentech and Pfizer.
No other potential conflicts of interest were reported.
Cost-Effectiveness of Pharmacologic Treatment Options for Women With Endocrine-Refractory or Triple-Negative Metastatic Breast Cancer
ARTICLE PUBLICATION DATE
2-Sep-2022
COI STATEMENT
Wheeler and Reeder-Hayes are members of UNC Lineberger, which has received institutional research funding from Pfizer. Gogate reported employment and stock and other ownership interests in Bristol Myers Squibb/Celgen. Rocque reported consulting or an advisory role with Pfizer, Flatiron Health and Gilead Sciences and receiving research funding from Carevive Systems, Genentech and Pfizer. No other potential conflicts of interest were reported.