Culture

DALLAS (SMU) - The discovery of the first juvenile dromaeosaurid lower jaw bone on the North Slope of Alaska supports a growing theory that some Cretaceous Arctic dinosaurs did not migrate with the seasons but were year-round residents, according to new research by SMU paleontologist Anthony Fiorillo. The research was published today in PLOS ONE. Prior to this find, only tiny dromaeosaurid teeth have been discovered in this region.

Dromaeosaurids are a group of predatory dinosaurs closely related to birds. Researchers have tended to believe that this group of dinosaurs migrated through the area but did not make their homes there.

"This is the first physical evidence that 70 million years ago, some dromaeosaurid nested in the area," Fiorillo says. "To withstand the rigors of migration, modern caribou need to be at least 80 percent of their adult length. Grown dromaeosaurids ranged from 6 to 9 feet. This baby would have been the size of a small puppy, much too young to migrate," he says.

Dromaeosaurids' small and delicate bones don't preserve well in the fossil record, which makes this discovery of a baby's jawbone particularly unique, Fiorillo says. But don't be fooled by their fine-boned stature. Velociraptors, the "Jurassic Park" dinosaurs that terrorized the kids in the famed kitchen scene, are members of this same sharp-toothed family, he says.

The partial jaw fossil that Fiorillo and colleagues studied, with one black erupted tooth, was found on a bank of the Colville River near the Arctic Ocean, about 250 miles north of the Arctic Circle. The location is part of the Prince Creek Formation, which existed as a coastal plain in the Late Cretaceous period with a climate similar to 21st century Seattle or Portland, Oregon. Trees, ferns and mosses flourished there, along with plant-eating dinosaurs, small mammals and the predators that ate them. Now the formation is home to the largest collection of polar dinosaurs in the world.

Paleontologists have long thought the Prince Creek Formation was once a dinosaur highway, with migrating hadrosaurs, ceratopsians and theropods crossing a land bridge between Asia and North America and dispersing across the continent. The discovery of this tiny portion of the tip of a dinosaur chick's jawbone helps prove that some dinosaurs made their home there.

Co-authors of the paper include Alfio Alessandro Chiarenza, Ronald S. Tykoski, Paul J. McCarthy, Peter P. Flaig, and Dori L. Contreras.

SMU paleontologist finds challenge, adventure and success in Alaskan wilds

For the last 22 years, Fiorillo has spent his summer camping on the riverbanks and mountainsides of Alaska, searching for fossils. But COVID-19 grounded the planned 2020 five-person expedition to Aniakchak National Monument, the most remote and least visited national park unit in the country. The team was planning to expand on its earlier successes studying dinosaur tracks, published last year in the journal PLOS ONE.

When Fiorillo first traveled to Alaska in 1998, dinosaur fossils had only been found in two areas of the state. The North Slope was home to just one kind of exploration - oil.

"When you looked at the geologic map of the area, the age of the rock was just the right age to find dinosaur fossils," he said. "Researching there sparked my intellectual curiosity and sense of adventure."

And like Fiorillos' muse, Arctic Village author Robert Marshall, "Blank spaces on maps have always fascinated me," he says. For Fiorillo, there is no sweeter sound than the fading roar of the fixed wing plane that has deposited his team, gear and provisions on an airstrip far from any road or civilization.

"It's hard to explain, it's liberating and freeing being completely on your own the way we are," he says.

The isolation also comes with challenges. Fiorillo and his teams have experienced floods, earthquakes, landslides, snowstorms and once, a bear that tried to get into his tent. In the early years, their only communication to the outside world was an air-to-ground radio that connected to a commercial plane passing overhead, of which there were few.

"If trouble comes, it's up to us to get out of it," he says.

Fiorillo's intellectual curiosity and love of adventure have paid off. The map of Alaskan dinosaur fossils is no longer blank. And after 22 years of Arctic research, Fiorillo has found that dinosaur fossils there are so prevalent, "You can't walk 10 steps without tripping over one."

Of the four Alaskan dinosaurs with names, Fiorillo has named two of them, a right given to the person who discovers the first of a species. He's the author of more than 150 scientific papers, abstracts and reviews, a collaborator on four books and author of Alaska Dinosaurs: An Ancient Arctic World, published in 2018.

Visitors to Dallas' acclaimed natural history and science museum, the Perot Museum of Nature and Science, are well aware of his work, he played a key role in the museum's development, serving as vice president of research and chief curator since 2014. He was curator of Earth sciences there from 1999-2014.

Fiorillo is now curator emeritus at the Perot Museum, and adjunct associate professor in the Huffington Earth Sciences department at SMU. Grounded this year by the coronavirus, he is ready to go back to Alaska.

"Very little was known about Alaskan dinosaurs when I first started going there," he says. "We've answered many academic questions, but we've raised even more new questions."

About SMU

SMU is the nationally ranked global research university in the dynamic city of Dallas. SMU's alumni, faculty and nearly 12,000 students in eight degree-granting schools demonstrate an entrepreneurial spirit as they lead change in their professions, communities and the world.

Contact: Nancy George, ngeorge@smu.edu, 214-768-7674, 972-965-3769, cell

Journal

PLoS ONE

PROVIDENCE, R.I. [Brown University] -- While immunotherapy -- a form of treatment that uses the body's immune system to recognize, attack and kill tumor cells -- has given hope to people across the globe, it fails in a significant proportion of cancer patients.

However, a new study published in the Nature journal Cell Death Discovery on Monday, July 6, suggests that blocking the tumor-promoting protein MDM2 could bolster immunotherapy's effectiveness.

"Immunotherapy has been one of the biggest breakthroughs in biomedical science and medicine of the last two decades," said Dr. Wafik El-Deiry, a professor of pathology and laboratory medicine and associate dean for oncologic sciences at Brown University. "But it has limitations."

Some people's tumors respond to immunotherapy initially and then relapse. Other patients experience pseudoprogression, where tumors appear to grow before eventually shrinking. And a third group -- between 5% and 29% of patients -- experience hyperprogression, which means that immunotherapy actually worsens their tumor growth.

El-Deiry hopes that blocking MDM2, either through gene-silencing or the MDM2-inhibiting drug AMG-232, could be especially helpful for people with hyperprogression.

Various studies have found that when the MDM2 gene is amplified -- meaning that cells contain too many copies of the gene -- or when the MDM2 protein is overexpressed because the gene is not being regulated properly, tumor cells tend to grow more quickly and are more resistant to immunotherapy. Researchers are still investigating exactly why this accelerated growth and resistance occur, but studies suggest that MDM2 can help tumors grow and evade the immune system through a variety of mechanisms. For example, MDM2 appears to inactivate the tumor-suppressor gene p53 and prevent immune cells from killing tumor cells, and it is also associated with higher levels of a tumor-promoting inflammatory protein called interleukin-6 (IL-6).

In their study, El-Deiry and his colleagues treated cell lines of MDM2-overexpressing ovarian cancer cells with the therapeutic AMG-232. The data show that AMG-232 allowed immune cells to kill the tumor cells much more efficiently and reduced levels of IL-6. These results suggest that MDM2 inhibitors could be combined with immunotherapy to enhance its effectiveness.

This study follows the recent launch of the Cancer Center at Brown University, where El-Deiry serves as inaugural director. The center builds on Brown's growing focus on translational science -- the practice of ensuring that breakthroughs in basic research are advanced to the point where they can make a meaningful medical difference for patients, and that urgent scientific questions identified in the clinic or among patient populations become research priorities in the lab. Faculty at the new center will take a broad-spectrum approach to research, from working to understand how cancer develops, grows and metastasizes, to developing new therapeutics for patients in a personalized way that addresses their needs ranging from risk through survivorship.

For this specific finding, El-Deiry hopes the study will lead to a clinical trial so the research team can further evaluate the safety and effectiveness of this novel treatment. With MDM2 amplification and overexpression implicated in a variety of cancers, he believes that AMG-232 (or similar drugs, including those that block both MDM2 and a related protein, MDMX) could be widely applicable -- and it could even benefit immunotherapy patients whose tumors have normal MDM2 levels.

"We think this might be a good approach to treat patients whose tumors are predicted to undergo hyperprogression, but I would say our results show that targeting MDM2 in combination with immunotherapy works well even if MDM2 is not amplified or overexpressed," El-Deiry said. "It's tapping into a vulnerability within tumors to help immunotherapy work better."

In addition to El-Deiry, other Brown University authors on the study were Ilyas Sahin, Shengliang Zhang, Arunasalam Navaraj, Lanlan Zhou, Don Dizon and Howard Safran. The study was supported by the Mencoff Family endowed professorship at Brown.

This news story was authored by contributing science writer Kerry Benson.

Genomics is crowding out ways of reducing inequality, has thwarted medicine from advancing justice, and is creating new forms of social classification and surveillance. These are key messages of For ''All of Us''? On the Weight of Genomic Knowledge, a new Hastings Center special report.

The overarching premise of the report is that genomic "can be a weight, a weight that has the potential to thwart--and historically has thwarted--medicine from genuinely advancing justice," writes Joel Michael Reynolds, co-editor of the report with Erik Parens, a senior research scholar at The Hastings Center. The report asks if the focus on genomics is crowding out other, more effective ways of reducing health inequity. It warns that genomic knowledge can shore up scientifically discredited conceptions of race, which further entrenches structural racism. The report also warns that the danger of treating social behaviors as genetic or based on racial classifications is that this kind of logic can spur on eugenics. The report also notes that the benefits of genetic advancements will likely go to the richest in society, further exacerbating inequality.

The special report highlights several ways that genomics can perpetuate inequality and structural racism:

Genomics is crowding out ways of reducing health inequity.

Despite mountains of data emphasizing the social and political nature of health disparities, the new focus racial difference in genomics has resulted in a shift from environmental causes to genetic causes.

Health disparities quickly become imagined to be the result of DNA differences, as opposed to the intergenerational health effects of societal racism.

Instead of measuring the environment and social conditions in meaningful ways, such as by studying how racial discrimination affects biology, genomics research reinforces the notion that race is determined by our genes.

Genomic knowledge will likely go toward helping privileged people make their lives a little bit longer or a little bit better.

The special report consists of 10 essays written by scholars in philosophy, social sciences, medical anthropology, and disability studies. The essays include:

Health for Whom? Bioethics and the Challenge of Justice for Genomic Medicine by Joel Michael Reynolds. In this to the special report. Reynolds writes that the report begins with the "conviction and hope that justice is at the normative heart of medicine and that it is the perpetual task of bioethics to bring concerns of justice to bear on medical practice." Summing up the special report, Reynolds writes that "taking the principle of justice seriously would lead us to better situate the gift and weight of genomics within the many practices for which we have evidence to bring about fairness and equity for human lives. To implement these practices will require not only significant biomedical efforts but also political efforts that push typical clinical and bioethical concerns beyond their historical orbit." Reynolds is an assistant professor of philosophy and disability studies at Georgetown University and the inaugural Rice Family Fellow in Bioethics and the Humanities at The Hastings Center.

Conceptualizing Race in the Genomic Age by Catherine Bliss. This essay argues that a concept of race that presumes that there are discreet genetic groups of white, black, Asian, Native American, and Pacific Islander is a fallacy that will always lead to social inequality. Bliss asks whether genomics can do more than merely avoid racism; can it contribute to antiracism projects? To promote social justice, she writes, "all of us across the sciences, throughout health policy, and in the wider public will need to reconceptualize race in terms of legacies of discrimination. We will need to shift our focus from molecular differences to social and political differences, especially when we conduct gene-environment analyses." Bliss is an associate professor of sociology at the University of California, San Francisco.

Does Solidarity Require ''All of Us'' to Participate in Genomics Research? by Carolyn P. Neuhaus. This essay interrogates the idea that Americans have an ethical obligation to participate in genomics research, as an act of solidarity, particularly the federal government's "All of Us," which aims to create precision medicine and improve the health of everyone. Neuhaus argues that while participating in research may be "a good thing to do," cultivating and expressing solidarity requires much more of us. Specifically, it requires recognizing another person or other creature "as, like ourselves, vulnerable to injustice and entails acting in ways that contribute to creating, reforming, and participating in institutions that are aimed at enhancing their flourishing." Neuhaus is a Hastings Center research scholar.

Why and How Bioethics Must Turn toward Justice: A Modest Proposal by Jenny Reardon. To create a genomics that offers more gifts than weights, Reardon argues, central attention must be paid to questions of justice and structural inequity. It will necessitate building novel coalitions and collaborations that turn the attention of bioethical governance away from narrow individual questions such as, "Do I consent?" and toward the broader collective question, is this just? Reardon is a professor of sociology and the founding director of the Science and Justice Research Center at University of California, Santa Cruz, and Hastings Center fellow.

According to the United Nations, about one-fifth of the world's population lives in areas where water is scarce. Therefore, technologies to produce clean water from undrinkable sources, such as seawater, river or lake water, and contaminated water, are urgently needed. Now, researchers reporting in Nano Letters have developed a wood-based steam generator that, with the help of bacterial-produced nanomaterials, harnesses solar energy to purify water.

A solar steam generator is a device that uses the abundant energy of the sun to separate pure water from its contaminants by evaporation. Many different versions of these devices have been developed, with varying efficiencies. To design better solar steam generators, researchers must find ways to improve light absorption, heat management, water transport and evaporation. Shu-Hong Yu and colleagues at the University of Science and Technology of China wanted to combine all four improvements in a single device. They chose wood as the basis of their generator because of its sustainability and porous structure, which allows rapid water transport.

The researchers made their device with the help of bacteria that produced long cellulose nanofibers, which bound the layers of the device together. The team added bacteria to the surface of a block of wood and allowed them to ferment. Then, they sprayed an aerosol of glass bubbles -- tiny hollow spheres that provide excellent thermal insulation -- onto the surface. The glass bubbles became embedded in the cellulose nanofibers produced by the bacteria, forming a hydrogel. Finally, the researchers added carbon nanotubes, which tangled with the cellulose nanofibers to form a light-absorbing, water-evaporating top layer. The device works by transporting water upward through the wood to the light-absorbing layer, which is heated by the sun. The water evaporates, and the steam is collected and condensed to produce pure water. The insulating layer of glass bubbles keeps heat from being transferred downward through the device and lost, and the nanoscale structures lower the energy required for water vaporization. As a result, the new device has a higher evaporation rate and efficiency than most existing solar steam generators.

This press release is in support of a presentation by Dr Mostafa Metwally presented online at the 36th Annual Meeting of ESHRE.

8 July 2020: An add-on treatment commonly offered to patients in preparation for IVF has proved ineffective in a large-scale randomised trial of more than 1000 women. Those who had endometrial scratch before their first IVF treatment were found to be no more successful than a control group receiving routine treatment. Endometrial scratch is an adjuvant procedure in which the lining of the uterus is "injured" (usually by a small biopsy) in the hope of improving embryo implantation,

This UK Multicentre Endometrial Scratch Randomised Controlled Trial is the biggest and most powerful study of the add-on so far reported. The results, says chief investigator Mostafa Metwally from Sheffield Teaching Hospitals and the University of Sheffield, UK, "provide conclusive evidence" that endometrial scratch is not beneficial in women having IVF for the first time. "It is time to stop this practice," says Dr Metwally, who will present the results online today at the 36th Annual Meeting of ESHRE.

Although some earlier studies have cast doubt on the efficacy of endometrial scratch, it is still commonly available and offered to IVF patients as an add-on treatment.(1,2) This study, however, because of its size, design and homogeneous population, now leaves no doubt over its findings. The trial was performed at 16 UK centres during 2016 to 2019 and involved more than 1000 women under 37 years of age having their first cycle of IVF. They were randomised equally to endometrial scratch, or no scratch, with primary outcome of the study being a live birth.

Results showed that live birth rate in the intervention group was 38.6% and in the routine treatment group 37.1%, with no statistical difference whatsoever. Secondary outcomes of the trial assessed clinical pregnancy rate, embryo implantation rate and obstetric complications. Again, there were no differences in these secondary outcomes between the scratch and no-scratch groups - with clinical pregnancy rate 42.6% in the former, and 40.6% in the latter.

Dr Metwally says the strength of the study lies in the homogeneous study population, which leaves results less open to bias. All the subjects were having their first cycle of IVF and were expected to be good responders to treatment. The scratch was performed in the mid-luteal phase of the cycle before their IVF began. The study was also powered to detect a 10% difference in outcome (a result considered to be practice-changing) but in these results the intervention was found to be of no value.

The study results come at a time when adjuvant treatments are under increasing scrutiny. A series of recent add-on reviews in one medical journal found that none of several with clinical, endometrial and laboratory applications had a strong enough evidence base for routine use.(3) And in Britain none of those on an official traffic-light list of 11 add-ons (including endometrial scratching) is thought worthy of a green light. Yet the belief persists that a scratch to the lining of the uterus causes an environmental response likely to encourage embryo implantation.

Despite the similarly discouraging results of several earlier studies, Dr Metwally notes that endometrial scratch remains widely offered in IVF clinics throughout the world. Indeed, a 2016 survey found that 83% of clinics in Australia, New Zealand and UK "are recommending endometrial scratching" to their IVF patients.(4)

Dr Metwally described these results as "very reliable for women having their first IVF cycle", a clearly defined study population and different from those in several earlier trials, some of which included patients with unsuccessful previous IVF treatments. "Our study is the largest and most conclusive study in women having first time IVF treatment," says Dr Metwally, "and the findings conclusively indicate that the practice of performing scratch in this group should stop."

* This study is funded by the National Institute for Health Research (NIHR) [Health Technology Assessment programme (project reference 14/08/45)]. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

Brain cancers have long been thought of as being resistant to treatments because of the presence of multiple types of cancer cells within each tumor. A new study uncovers a cancer cell hierarchy that originates from a single cancer cell type, which can be targeted to slow cancer growth.

The research was led by Dr. Kevin Petrecca, a neurosurgeon and brain cancer researcher at The Neuro (Montreal Neurological Institute and Hospital) of McGill University, part of the McGill University Health Centre.

The study, which is the largest ever single cancer cell RNA sequencing project, included 55,000 glioblastoma cells and 20,000 normal brain cells. The team found that there are five main cancer cell types within each tumor, and these cancer cell types are similar to the cell types that are in the normal human brain.

For the first time, researchers detected what they describe as a progenitor glioblastoma stem cell (GSC) -- a cell type from which all other cancer cells develop. They showed a cellular hierarchical organization to the cancer which originates from progenitor GSCs.

The team found that progenitor GSCs divided much more than the mature cancer cells and make up the vast majority of dividing cells in the tumour, despite making up a relatively small proportion of the total tumor. These rapidly dividing cells are the earliest detectable cancer cells in the hierarchy and so make a promising target for therapy.

After identifying molecular vulnerabilities in progenitor GSCs, the researchers then targeted these and found that progenitor GSC survival and proliferation decreased as a result. In preclinical disease models, this reduced tumour growth and increased survival.

"Our work has gone a long way to resolve the complexity of glioblastoma heterogeneity, and provides a new framework to reconsider the nature of glioblastoma," says Dr. Petrecca "As part of this work, our study also shows, in contrast to decades long dogma, that glioblastoma stem cells are the most rapidly dividing cancer cells in the tumor, and we identified new ways to target these cells. There is still much work to be done. Understanding how these cancer cells interact with the cancer microenvironment is not well understood in this disease, but this study serves as a good starting point to begin to understand how glioblastoma originates and evolves prior to treatments."

Durham, NC - Results of a clinical trial released today in STEM CELLS Translational Medicine indicates that breast augmentation in patients treated with fat grafts enriched with autologous adipose-derived stem cells (ASCs) had significantly superior results compared to those treated with non-enriched grafts.

The clinical trial, conducted by a multi-institutional group of researchers led by Stig-Frederik T. Kølle, M.D., Ph.D., chief surgeon in the Department of Plastic Surgery at Aleris Hamlet Hospitals in collaboration with the stem cell research and production facility Stemform (Copenhagen), was designed to examine whether ex vivo-expanded ASC-enriched fat grafts for breast augmentation could improve the results of conventional lipofilling while offering a safe procedure. It is the first study to investigate the effect of expanded ASCs on large-volume fat grafting in a clinically relevant setting.

"The repair of disfiguring volume defects of the female breast following cancer resection and congenital anomalies are secondary to the aging process and breast feeding represents a large and growing patient population with an increasing demand for natural solutions to address their surgical needs," Dr. Kølle said. "Silicone implants are the gold standard for correcting breasts aesthetically, but they can have significant complications, and some have been associated with lymphoma. With the goal of an aesthetic and natural appearance, patient safety and satisfaction, an alternative strategy for breast augmentation and correction is autologous fat grafting."

Autologous fat is gaining acceptance as an ideal soft tissue filler because it is biocompatible, versatile, non-immunogenic, and readily available. Also, harvesting fat through liposuction involves minimal trauma. However, clinical outcomes have varied extensively, and reported retention rates for transferred fat range from 25 to 80 percent, regularly necessitating repeated procedures.

Methods to increase graft retention are needed to make the procedure a reliable and attractive alternative to implants, especially in slim patients with limited fat resources. In this respect, cell enrichment has been shown to have promise. Animal and human studies have demonstrated that enrichment with ex vivo-expanded ASCs markedly improved the residual volume and histological appearance of fat grafts.

In the study reported here, 12 healthy women with small breasts who had a desire for augmentation were divided into two groups. Six received ASC-enriched fat grafts, while the control group (also six patients) received conventional, non-enriched fat grafts. The patients were followed for a minimum of 18 months and will also be given a five-year follow-up safety evaluation.

Total breast volume was determined by MRI both preoperatively and again after four months. Clinical results were also evaluated by 10 independent board-certified plastic surgeons. Photos of the patients before the operation, at four months and 18 months after the operation, were presented blinded and at an equal profile to each surgeon and assessed by the question: "If you performed one fat transplantation for breast augmentation, how satisfied would you be with the retention/survival and the cosmetic result?"

"Both the MRI and the plastic surgeons' assessments showed significantly better clinical results in the ASC-treated group than in the controls receiving non-enriched fat grafts," Dr. Kølle reported. "With a median survival of 80.2 percent of the total injected volume in the ASC group (compared to 45.1 percent in the control group), and a median enlargement of 2.6 times the initial breast volume, no second augmentation procedure was needed.

"This study demonstrates a safe profile for the usage of adipose-derived stromal cells," he added. "The results are likely transferable to most soft tissue augmentations and may, therefore, be beneficial to a broad spectrum of patients."

"The outcomes of this first clinical trial comparing breast augmentation in patients treated with fat grafts enriched with adipose-derived stromal cells to those treated with fat grafts alone are encouraging and indicate this procedure is safe and effective," said Anthony Atala, M.D., Editor-in-Chief of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. "Such procedures could someday offer a valid alternative for patients who currently are treated with silicone breast implants."

Hearing is widely thought to be the last sense to go in the dying process. Now UBC researchers have evidence that some people may still be able to hear while in an unresponsive state at the end of their life.

This research, published recently in Scientific Reports, is the first to investigate hearing in humans when they are close to death.

Using electroencephalography (EEG), which measures electrical activity in the brain, the researchers analyzed data collected from healthy control participants, from hospice patients when they were conscious, and from the same hospice patients when they became unresponsive. The patients were receiving palliative care at St. John Hospice in Vancouver.

"In the last hours before an expected natural death, many people enter a period of unresponsiveness," says study lead author Elizabeth Blundon, who was a PhD student in the department of psychology at the time of the study. "Our data shows that a dying brain can respond to sound, even in an unconscious state, up to the last hours of life."

This new insight into the dying brain's response to sound can help family and friends bring comfort to a person in their final moments.

The researchers introduced study participants to various patterns of common and rare sounds that changed frequency. When the rare tone pattern occurred, both groups responded by giving a pre-arranged signal.

The researchers monitored the brain's response to those tones using EEG and found that some dying patients responded similarly to the young, healthy controls--even when they were hours away from death.

"We were able to identify specific cognitive processes from the neuro-typical participants as well as the hospice patients," says Lawrence Ward, a professor in the department of psychology at UBC. "We had to look very carefully at the individual control participants' data, to see if each one of them showed a particular type of brain response before we felt confident that the unresponsive patient's brain reacted similarly."

This study was adapted from a European study that explored brain responses to sound in individual healthy participants, and in minimally conscious and unresponsive brain-injured patients. The UBC researchers applied a similar paradigm to actively dying unresponsive patients.

Blundon and Ward collaborated with Dr. Romayne Gallagher, a palliative care physician at St. John Hospice who has since retired. The research required patients to give their consent in advance. Thirteen families participated and brain recordings were obtained from five patients when they were unresponsive.

In Gallagher's 30 years of treating dying patients, she has witnessed positive reactions in people when loved ones spoke to them in their final moments. Gallagher and her colleagues often wondered if hearing was the last sense to go. She contacted Ward to see if this theory could be proven.

"This research gives credence to the fact that hospice nurses and physicians noticed that the sounds of loved ones helped comfort people when they were dying," says Gallagher. "And to me, it adds significant meaning to the last days and hours of life and shows that being present, in person or by phone, is meaningful. It is a comfort to be able to say goodbye and express love."

Blundon says what while the evidence of brain activity supports the idea that a dying person might be hearing, they can't confirm whether people are aware of what they're hearing.

"Their brains responded to the auditory stimuli, but we can't possibly know if they're remembering, identifying voices, or understanding language," says Blundon. "There are all these other questions that have yet to be answered. This first glimpse supports the idea that we have to keep talking to people when they are dying because something is happening in their brain."

Knee replacements are a huge burden on society and individuals from all walks of life. A major global systematic review has identified the common jobs - paid and unpaid - that may be putting people unknowingly at risk.

A study by the Universities of Sydney, Oxford and Southampton reveals there is a need for targeted work health and safety practices to extend beyond physically burdensome jobs; regulators and insurance companies should take account of the high number of medium-risk occupations and that unpaid roles also rate highly.

It is the biggest meta-analysis and systematic review of the potentially debilitating knee osteoarthritis (OA) - comprising 71 studies and almost one million people - and the first systematic review into the association between job 'titles' and knee OA.

Increased risk was found in agriculture workers, construction workers, miners, service workers, houseworkers (i.e. housewives) and cleaners.

The findings are published today in the prestigious journal Arthritis Care and Research.

The senior author, Professor David Hunter, of the University of Sydney's Florance and Cope Chair of Rheumatology, Institute of Bone and Joint Research in the Kolling Institute, said the research, while not focusing on the important role of exercise in combatting this common lifestyle ailment, identified the jobs that placed high-to-moderate stress on vulnerable knees.

"Knee osteoarthritis is a leading cause of loss of work and disability worldwide and can necessitate invasive surgery including total knee replacement, so preventing occupational hazards is critical," Professor Hunter said.

"The burden is increasing, with projections of osteoarthritis that affects one in eight people jumping 50 percent within 15 years , in large part attributable to lifestyle issues such as growing rates of obesity and reduced exercise."

Lead author Dr Xia Wang, also from the Institute of Bone and Joint Research, Faculty of Medicine and Health, said although research has previously identified frequent kneeling, squatting and heavy lifting - particularly in agriculture and construction - as risk factors, this comprehensive study highlighted occupational risks generally.

"With people working and living longer knee osteoarthritis is an area of concern even in service-focused developed nations, including in mid-risk occupations such as cleaning and full-time, unpaid housework and caring," she said.

Findings include:

- Floor-layers, bricklayers and carpenters have ~2.5 times increased odds compared to sedentary workers.

- Agricultural workers had up to 64% increased odds; builders and construction workers had increased odds of 63%.

- Houseworkers (unpaid) have up to 93% increased odds.

- Occupations like commerce, forestry or fishery workers, machine operators, plumbers, electricians, technicians, postmen were not found to be statistically significantly associated with knee OA.

- The following activities were identified as increased risk: excessive kneeling, squatting, standing, lifting and climbing stairs.

Dr Thomas Perry, co-lead author and postdoctoral researcher at the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, said: "Our collaborative work has been critical in understanding the relationship between work-place physical activities and knee osteoarthritis. We hope these findings will help guide the future development of work-place personal protective equipment."

Professor Cyrus Cooper, director of the MRC Lifecourse Epidemiology Unit, University of Southampton, said: "Further evaluation of this issue will ensure that occupational risks of knee osteoarthritis - the commonest joint disorder worldwide - are minimised."

Meconium--the earliest stool of an infant--is composed of materials ingested during the time the infant spends in the uterus. A new study published in Pediatric Obesity found that the types of normal bacteria found in the meconium may predict an infant's likelihood of later developing obesity.

In the study of 212 newborns, children who became overweight at 3 years of age differed in their meconium bacterial makeup from those with normal weight, having a higher proportion of bacteria in the Bacteroidetes phylum (29% versus 15%).

The concept of fetal microbiome is controversial and the colonization process after birth is better understood than the possible fetal colonization; however, there are many prenatal factors affecting the microbial composition of the baby's first stool, such as the mother's use of antibiotics during pregnancy and biodiversity of the home environment during pregnancy," said corresponding author Katja Korpela, MD, of the University of Oulu, in Finland. "It is very interesting that the microbiome formed before birth is possibly linked to a child's subsequent weight status."

In a recent study from Singapore, early access to pension wealth was associated with improved health status. The findings are published in Economic Inquiry.

Singapore has a unique policy that allows individuals to withdraw a proportion of their pension savings after their 55th birthday, which relaxes individuals' borrowing constraints. To examine its health impacts, investigators analyzed monthly survey data from 2015 to 2019, comparing individuals' self-reported health status before and after their 55th birthday.

The results indicated that early access to pension wealth improves overall health status. Detailed analyses of underlying mechanisms showed that early access to pension wealth might boost health by improving psychological well-being.

"Since allowing the early partial withdrawal of pension balances does not necessarily increase the fiscal burden of the government, our results imply that flexible access to pension wealth could be a cost-effective policy to improve the health of middle-aged individuals," said co-author Kanghyock Koh, PhD, of Korea University.

When it comes to soils, proper identification is key. Identification allows scientists to determine the story behind the soil: how it formed, how it behaves in different scenarios, and how valuable it may be to certain plants and animals.

Soil classification, or scientific identification, can also help determine if the soil needs extra attention and resources for protection. For example, certain soils may not be safe for hiking, could be home to an endangered species, or foster a unique ecosystem like wetlands.

However, soil classification is complex. Soil characteristics include color, texture, mineral composition, air and water content, and much more. Each of these characteristics can give added details to solve the story behind the soil.

Many soils are simple for trained soil scientists to identify. But Karen Vaughan of the University of Wyoming and her team dug in to investigate an area of soil along the central coast of California that had some peculiar characteristics.

"The reason for this research site really comes from long ago in a wetlands field lab," she says. "Students kept saying the soil didn't meet all the field indicators of hydric -- or wetter -- soils. I thought, it has to. It's wet and there's plenty of water-loving vegetation. Then I realized it must be a problematic soil, so we set up this experiment to figure it out."

Vaughan's experiment consisted of studying how dark the color of the soil was, as well as its water content, vegetation, and chemical composition. Looking at how wet the soils seemed, the vegetation that grew there, and microbes that lived there, a scientist would think they were wetland soils.

However, other characteristics of the soil, such as its dark color, confused the researchers because it was so similar to the surrounding drier soil. This is where a way to analyze soil color more precisely, called the profile darkness index, was helpful. It allowed them to properly classify the soils.

Soil classification is usually a pretty exact science. Hydric soils have a specific set of characteristics. One of the key characteristics of hydric soil is a pale, light greyish color. As a result of the uniquely dark color, they could be mistakenly identified as drier soils and not meet the requirements of wetlands.

More clues for soil classification can sometimes be found in the landscape. Landslides are common on these cliffs, which cause soil to fall and be deposited in other areas. Often, these landslides result in depressions where a soil might be wetter than its surroundings.

"We get these situations where the soil characteristics don't match features we usually see in wetter soils," Vaughan explains. "This is, for example, because the transported soils inherited darker colors from the parent material. If someone looked at these soils, they would assume they are not as wet as they are. They then would not classify these areas as wetlands, despite them performing as wetlands."

"This kind of proper identification is important so the wetlands can be better conserved," Vaughan says. "If researchers don't know about them, they can't be protected."

This is because wetlands are so beneficial to the environment. They can help store water to protect against floods and erosion, as well as improve water quality. They also serve as a place for important plants and animals to live. Of course, they are also beautiful to observe when hiking out in nature.

"Soils tells the story of an ecosystem," she says. "If we look to the soil, we can understand ecosystem function."

New research from the UBC Sauder School of Business shows that people are 30 per cent more likely to donate their assets when faced with their own mortality.

The study examines how people respond to "mortality salience" -- that is, the uniquely human awareness that they're going to die.

Earlier studies have shown that some people console themselves by acquiring more material possessions -- in other words, they subscribe to the notion that "He who dies with the most toys wins."

But the new research shows that people can also express a desire to pass important possessions on to others, because it gives them a kind of immortality the researchers call "transcendence."

"It sounds dramatic, but it's the idea that you can live on longer, symbolically through something else," says study co-author and UBC Sauder Professor Katherine White, who co-authored the study with UBC Sauder Professor Darren Dahl and Lea Dunn, assistant professor of marketing at the Foster School of Business at the University of Washington. "So, if a product or a possession is somehow linked to your identity and you pass that on to others, it could potentially have this ability to transcend the self."

The researchers first launched the study several years ago, long before the threat of COVID-19 had people more closely considering their mortality, and updating wills and planning estates.

"For many people, that mortality salience is much higher now, for better or for worse. People are just more aware of how fragile life can be," says Dahl. As a result, adds White, more people are likely thinking about the idea of symbolic immortality and where their possessions will go when they pass on.

To conduct the experiment, 512 participants were asked to arrive at the lab with a book they might consider giving away. One group was then given a task that made them contemplate their deaths, while the other considered what their typical day was like.

Later, participants were asked if they wanted to donate their book to charity; some were also offered the chance to write an inscription in the book and sign it, making the offering more personal. No researchers were present when participants made their decision to ensure there was no pressure to donate.

"The people who had contemplated their death were more than 30 per cent more likely to give away the product -- particularly when they had connected it to themselves," says White.

"They're much more likely to donate it after they have somehow connected it to their identity."

However, the effect goes away if the item may be broken up or recycled, thereby losing its perceived potential for transcendence.

"Let's say you're passing on a car or a motorcycle. If it's broken up into pieces and sold off as parts, it's not the same as if your specific car or your specific product was left to endure," says Dahl. "The specialness of it, and the fact that it represents you, is broken up, and you're not a whole entity sticking around."

The effect also didn't work on people who had already satisfied that desire for transcendence through other channels.

White says the findings could be helpful to charitable organizations looking for people to donate a portion of their estates. "Anything they can do to connect the self to something that's more lasting will help," says White. "So, it could be something like a plaque or a mural or a somewhat permanently displayed list of donors -- just a tangible representation of the self that's going to continue to exist."

Companies can also use transcendence as a selling point by marketing products as having high emotional value or being precious and irreplaceable family heirlooms.

PHOENIX, Ariz. -- July 8, 2020 -- A groundbreaking study published today and led by the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, identifies unique lung cells that may drive Idiopathic Pulmonary Fibrosis (IPF), a deadly lung disease that affects hundreds of thousands of Americans, and for which there is no cure.

This is one of the first comprehensive looks at lung cells using a technology called single-cell RNA sequencing. Instead of examining a mash-up of many cells from a tissue sample, single-cell sequencing allowed researchers in this study to closely examine the individual cells that make up the lungs; to identify their function, and ultimately understand the molecular changes that may be driving the disease.

Using this method, researchers identified five unique cells types associated with lung fibrosis, which could potentially lead to earlier diagnosis and therapeutic drug targets.

The study's initial findings, published today as the cover story for the journal Science Advances, are the first under a combined $6.1 million in federal grants aimed at uncovering the origins of lung disease, including IPF, the nation's most common and severe form of fibrotic lung disease. An estimated 50,000 Americans, mostly middle-aged and older adults, are diagnosed each year with IPF. Most die from respiratory failure within five years.

In collaboration with Vanderbilt University Medical Center (VUMC), researchers analyzed tissue samples from 20 lungs with pulmonary fibrosis provided by the Norton Thoracic Institute and VUMC, and tissue samples from 10 healthy lungs provided by the Donor Network of Arizona and the Tennessee Donor Services.

Dr. Nicholas Banovich, an Assistant Professor in TGen's Integrated Cancer Genomics Division and co-senior author of the study, said the most interesting finding is the characterization of cells called KRT5-/KRT17+, which appeared in the epithelium, or protective lining of the lungs, but only in individuals with pulmonary fibrosis.

"These cells are incredibly unique as they are clearly epithelial, but are also producing collagen and components of extra-cellular matrix (ECM), which make scar tissue," Dr. Banovich said, "They are directly contributing to fibrosis." These cells also share characteristics of both the airway and alveolar epithelium, the respiratory membrane that allows the exchange of gases.

Another of the study's most interesting findings is the high degree of plasticity, the ability of a cell to share characteristics with multiple classically defined cell types, in the lung epithelium.

"Classically, the field used a small number of genes to determine cell types. With the single cell RNA sequencing approach, we find that it is often hard to draw a firm line between different types of cells," Dr. Banovich said. "Instead of thinking of them as discrete cell types, we should think of them more along a continuum, and given the right stimulus, these cells can change their state."

In addition to the KRT5-/KRT17+ cells, the study identified a cell type marked by the gene SCGB3A2. These cells are similar to club cells -- an epithelial cell that lines the airways -- yet are found almost exclusively in in pulmonary fibrosis. Unlike other airway epithelial cells, it appears these cells are able to transform into type 1 alveolar cells (AT1) -- the cells where oxygen is taken into the body, and through which carbon dioxide is expelled -- in an effort to repair damage to the lung.

"In addition to becoming AT1 cells, our results suggest the SCGB3A2+ cells can also become the KRT5-/KRT17+ cells. It actually appears that, during the transformation into AT1 cells, the process is being hijacked and instead of helping repair the lungs these cells are pushed toward this weird pro-fibrotic epithelial cell that continues to drive fibrosis," Dr. Banovich said.

Two other cells unveiled by the study are distinct subsets of fibroblasts, the cells that form normal connective tissue and scar tissue in the lungs, marked by high levels of the genes PLIN2 or HAS1. These cells are also limited to pulmonary fibrosis.

IPF is a progressive and irreversible disease characterized by a dry cough, fatigue, aching muscles and joints, and ever worsening shortness of breath. IPF and PF both scar and stiffen the interstitium -- the delicate lace-like network that supports the lungs' tiny air sacs. IPF has both genetic and environmental risk, but the exact cause is unknown and current treatments short of a lung transplant only slow disease progression. Lung transplants are radical surgeries that usually require months of waiting for available organs, and often require a long and sometimes agonizing recovery.

The study acknowledges the help of: 10x Genomics and the Chan Zuckerberg Initiative in developing technology optimizations of the single-cell RNA sequencing; and the patients and organ donors who made this work possible.

Below please find a summary and link(s) of new coronavirus-related content published today in Annals of Internal Medicine. The summary below is not intended to substitute for the full article as a source of information. A collection of coronavirus-related content is free to the public at http://go.annals.org/coronavirus.

Quantifying and Interpreting Treatment Effects in COVID-19 Studies

Trials evaluating treatments for COVID-19 often use the time to a positive outcome as a key end point. In the presence of death as a competing risk, commonly used survival analysis techniques may not be appropriate. Using examples from two recent trials of treatments for COVID-19, the authors from Harvard University discuss issues with the current practice and present alternative, more clinically interpretable approaches. Read the full text: https://www.acpjournals.org/doi/10.7326/M20-4044.

Media contacts: PDFs for these articles is not yet available. Please click the link to read the full text. The lead author, Jason Lyell Vassy, MD, MPH, can be contacted directly at jvassy@partners.org.