Culture

The ability to "see" the inner workings of structures (organelles) within cells, in real time, offers the promise of advancements in disease diagnosis and treatment. Organelle dynamics drive the self-efficient micro-world of cells, but current super-resolution microscopy techniques used to track these interactions have limitations.

Now an advanced technique called SPOT (Spectrum and Polarization Optical Tomography) is giving researchers a "street view" of the vital lipid membranes surrounding organelles and by so doing opens up the opporutnies to study the sophisticated world of lipid dynamics.

The researchers say it's a significant development, building on earlier work on super-resolution polarization microscopy.

The research, published in Nature Communications was developed through a collaboration between University of Technology Sydney-Southern University of Science and Technology (UTS-SUStech) Joint Research Centre for Biomedical Materials & Devices, and Peking University.

Lead author Dr Karl Zhangao from UTS-SUSTech Joint Research Centre said that lipid membranes surround most organelles and play a significant role.

"Their shape, composition and phase synergistically regulate biophysical membrane properties, membrane protein function and lipid-protein interactions."

"However it is challenging to observe such a level of complexity due to their similar chemical composition," he said.

Simply using one dye that universally stains the lipid membranes, SPOT can simultaneously reveal lipid membrane morphology, polarity, and phase from measuring the intensity, spectrum, and polarization, respectively. Combined with lipophilic probes, the team successfully revealed more than ten types of organelles simultaneously, and their sophisticated lipid dynamics.

Using the new imaging platform established at SUStech, researchers observed the multi-organelle interactive activities of cell division, lipid dynamics during plasma membrane separation, tunneling nanotubules formation, and mitochondrial cristae dissociation.

"This is the first time researchers have been able to quantitatively study the lipid heterogeneity inside subcellular organelles," senior author Professor Dayong Jin says. Professor Jin is Director of UTS-SUStech Joint Research Centre and Director of UTS Institute for Biomedical Materials and Devices.

"This is a very powerful tool for super-resolution imaging the inner working of each single cells, that will advance our knowledge in understanding how cells function, diagnose when a "factory" or a transportation doesn't work properly within the cell, and monitor the progression of disease," Professor Jin said

"With such information it isn't too big a leap to identify pathways for potential drug treatments, as well as examine their efficacy right on the SPOT" he said.

Matching prices aren't the only reason oysters and champagne pair so well. According to a study published by the University of Copenhagen today, an uncanny umami synergy makes the combination of yeast-brewed bubbly and fresh molluscs a match made in heaven for some. Ironically, the new knowledge could help us consume more vegetables in the future.

Oysters and champagne are considered a perfect pairing. Now, researchers from the University of Copenhagen's Department of Food Science have found flavours in a range of champagnes and variety of Danish oysters that for the first time provide the scientific explanation for why these two foods complement one another so well.

"The answer is to be found in the so-called umami taste, which along with sweet and salty, is one of the five basic flavours detectable to human taste buds. Many people associate umami with the flavour of meat. But now, we have discovered that it is also found in both oysters and champagne," states Professor Ole G. Mouritsen from the Department of Food Science at UCPH.

In champagne, dead yeast cells contribute greatly to an umami flavour (glutamate). And as for oysters, the umami emerges from the mollusc's muscles (nucleotides).

"Food and drink pair well when they spark an umami synergy from combinations of glutamate and certain nucleotides. Champagne and oysters create a notably synergistic effect that greatly enhances the taste of the champagne. Furthermore, champagne contributes to the overall impression with, for example, its acidity and bubbles. That explains the harmony of these two foods," explains PhD student Charlotte Vinther Schmidt, the study's lead author.

Could get people to consume more vegetables

Besides the more luxurious example of oysters and champagne, the professor also points to ham and cheese, eggs and bacon and tomato and meat as gastronomic companions with umami synergy.

The professor believes that this synergy and taste is important to us humans for food choices. According to him, we are evolutionarily encoded to crave umami, as it is a sign of protein-rich food that is important to our bodies.

The encoding may be responsible for us being less enthusiastic about eating umami-less vegetables.

"Understanding the umami principle is particularly important because it can help get us to eat more vegetables. By being cognizant of umami synergy, one can make any vegetable tasty. And, it is my firm belief that if we want more people to eat more vegetables, we need to deal with the fact that greens lack umami," says Ole G. Mouritsen.

Local oysters and old champagne

For the ultimate combination of New Year's Eve oysters and champagne, Professor Mouritsen suggests native Danish Limfjord oysters and an older vintage champagne.

"One gets the most bang for the buck and best taste experience by tracking down flat Limfjord oysters and an unfortunately slightly more expensive bottle of older champagne. Older vintage champagnes have more dead yeast cells, which provide more umami. And Limfjord oysters contain large quantities of the substances that give umami synergy. Still, one shouldn't hesitate from purchasing the invasive Pacific oysters that are harvested in the same area as our native Limfjord species. They too can share an umami synergy with champagne, as the study shows," says Mouritsen

The research was published in Scientific Reports and conducted by Charlotte Vinther Schmidt, Karsten Olsen and Ole G. Mouritsen of the University of Copenhagen's Department of Food Science.

Facts:

In the study, the researchers examined a variety of champagnes, along with both Limfjord oysters and Pacific oysters. The study marks the first time that a scientific explanation has been provided for why oysters and champagne pair so well.

It is the combination of the amino acid glutamic acid and nucleotides from the breakdown of muscles from fish, molluscs and shellfish, for example, that greatly enhance umami taste.

The umami taste is derived from the concurrent binding of the salt (glutamate) of a free amino acid (glutamic acid) along with nucleotides to the umami receptor found in the taste buds of our tongues and in the oral cavity.

RIVERSIDE, Calif. -- Last year, researchers at the University of California, Riverside, identified the early origins of neural crest cells -- embryonic cells in vertebrates that travel throughout the body and generate many cell types -- in chick embryos. Now the researchers have used a human model to figure out when neural crest cells acquire distinctive molecular and functional attributes.

The study, published in Stem Cell Research, provides new insight into the formation of neural crest cells and outlines transient prospective stages in their development. It also shows the neural crest lineage is distinct from pluripotent stem cells.

The neural crest is an important embryonic cell population in the developing embryo that generates cells such as neurons, glia, and melanocytes, along with cells that make up bone and cartilage. Its improper development is linked to a wide range of pathologies, from craniofacial malformations such as palate clefts to aggressive cancers such as melanoma and neuroblastoma.

"Defining the molecular signature required for the formation of the neural crest better equips us to understand human neural crest related pathologies and develop diagnostic and therapeutic efforts," said lead study author Maneeshi S. Prasad, an assistant project scientist in the lab of Martin I. Garcia-Castro, an associate professor of biomedical sciences at the UC Riverside School of Medicine. "The knowledge of the precise time and molecular signals involved, when exactly the neural crest acquires the potential to form jaw and tooth cells, for example, will enable scientists to replicate and modulate their potential in stem cell therapies designed to aid regenerative craniofacial repair approaches, among many others."

The study used a robust human model of neural crest formation to demonstrate a fast transition from the pluripotent stem cell state to the neural crest precursor state. According to this model, a sequential loss of pluripotency markers occurs during the pluripotent stem cell state as cells transition to neural crest cells.

"We address the precise timing when pluripotent stem cells diverge toward the neural crest cell lineage by exploring the distinctive molecular and functional attributes of early neural crest cells -- something that had never been established," Prasad said. "We also identified unique molecular signatures during the transition stages of neural crest formation from pluripotent stem cells."

The researchers provide a high-resolution temporal map of gene expression and epigenetic changes with well-defined stages of neural crest formation they say should be a valuable resource for scientists identifying and studying the role of various genes involved in human neural crest formation.

Neural crest cells have been thought to originate in the ectoderm, one of the three germ layers formed in the earliest stages of embryonic development, but their capacity to form derivatives, such as bone- and tooth-forming cells, are in conflict with fundamental concepts in developmental and stem cell biology.

Garcia-Castro noted the study also establishes a novel in vitro specification test to determine the differentiation capacity of specified neural crest cells into other germ layers such as mesoderm and endoderm cell types. The specification test involves exposing the potentially specified cells to precise level of signals that stimulate the formation of other germ layers such as mesoderm and endoderm from pluripotent embryonic stem cells.

"Our work demonstrates that neural crest cells depart from the pluripotent stem cell state soon after the activation of Wnt signaling, an ancient and evolutionarily conserved pathway that regulates crucial aspects of the cell," he said. "Importantly, using our novel specification test we found that prospective neural crest cells lose the mesodermal and endodermal potential characteristic of pluripotent stem cells just hours upon their induction."

Garcia-Castro and Prasad were joined in the research by postdoctoral fellow Rebekah M. Charney and undergraduate researcher Lipsa J. Patel.

The research was funded by the National Institutes of Health.

The title of the research paper is "Distinct molecular profile and restricted stem cell potential defines the prospective human cranial neural crest from embryonic stem cell state."

The number of people who went missing during the first national lockdown in England fell by over a third, compared to data from the previous year. However, a new report out today shows that those who did go missing were deemed more vulnerable and at higher risk.

Researchers from the University of Portsmouth and University of Liverpool worked with six police forces from across the UK, to understand the impact of lockdown on missing people and recommend changes for the future.

Missing people are one of the most challenging issues for modern police forces, with the number of reported cases reaching 382,960 in 2018/2019 (NCA, 2020). The recent pandemic, and the resultant national as well as localised lockdowns, have placed unique demands on the emergency services (WHO, 2020).

The study aimed to compare the characteristics of missing people cases reported to participating forces during the period of the COVID-19 lockdown in England, with sample of cases taken from the same time period last year. The sample comprised of reports of adults and children who went missing between 23rd March 2020 until 20th May 2020, and the same time period in 2019.

As expected, the lockdown period led to a substantial reduction in the overall number of missing persons. There was a 35% decrease in missing children reports and 36% reduction in reports of missing adults.

However, the research also highlighted that those who went missing were more likely to be high risk of harming themselves or others. Adults who went missing during this period were more prone to mental health issues; domestic abuse; have relationship, drug or alcohol problems; or have a history of self-harm or suicidal thoughts.

Dr Karen Shalev Greene, Reader in Criminology, Director of the Centre for the Study of Missing Persons, University of Portsmouth explains: "The reduction in missing people is entirely expected, it is much harder to go missing, when the country is locked down. However, what is significant about these figures is it highlights how desperate some people must have been."

"The report emphasises the vulnerability of people that go missing during lockdown. Perhaps they live in situations that impact their mental health more making them determined for freedom. Whatever the reason, this is a reflection of society as a whole, including criminal organisations, exploitation, vulnerability and those that need support. To help prevent high risk missing adults from going missing the response needs to be multi agency. Efforts should also focus on after care and support once they return."

The report also highlighted that children were more likely to be classified as low risk during lockdown. The reason for this needs further investigation and understanding.

Dr Freya O'Brien, Senior Lecturer in Psychology, University of Liverpool, explains: "Particular attention should be given to understanding the reasons why children from care homes frequently went missing during lockdown and why children travelled long distances. One theory is that children in care were trying to get home to their families. It is important to bear regional differences in mind. Each force should study the patterns of missing in their force and consider local context."

National Police Chiefs' Council Lead for Missing People, Assistant Chief Constable Catherine Hankinson, said: "This research helps us to understand the changing trends in missing people and the different reasons they went missing during the first lockdown. The trend in more incidents being categorised as high risk suggests some of us really struggled with being isolated from our normal support networks. Police and our partners in health, social care and local authorities need to learn from that experience and consider how we can support people, particularly those with mental health issues, through ongoing restrictions.

"The research found that missing children were more likely to be categorised as low risk which is partly because some of them were reported missing for breaking the lockdown rules but then often returned safe and well after a short time. However, we will closely consider the research in the context of child exploitation, county lines and organised crime. Police are already aware of how these criminals are changing the way they operate but there is always more to do and we're committed to tackling those who are intent on causing harm to our communities and young people.

"Our work with partners in local authorities and social services will consider how we maintain contact with vulnerable children during any further restrictions, as it is vital we all do everything possible to protect them from abuse and exploitation at home."

T cell responses are critical for providing early control and clearance of many viral infections, but there remain many unknowns concerning T cell immunity in COVID-19. Some T cell responses may even have a detrimental impact on the clinical outcome and contribute to long COVID, a phenomenon that affects roughly 10% of COVID-19 patients, causing them to experience an array of symptoms for a month or longer. In this Perspective, Annika Karlsson and colleagues discuss unresolved questions surrounding T cell immunity against SARS-CoV-2 infection, including one that's important to consider for development of T cell-targeted vaccines: are T cells critical to generate durable immunity to the virus? Other unknown areas include the roles and longevity of SARS-CoV-2-specific memory T cells; the location and function of tissue resident memory T cells; and whether preexisting immunity to SARS-CoV-2 via cross-reactive T cells helps protect against the virus or, rather, exacerbates harmful inflammation. As well, scientists have yet to determine how T cell responses differ depending on disease severity (mild or asymptomatic versus severe or long COVID), and whether genetic factors, such as a patient's HLA type, could influence disease severity. Filling these gaps in knowledge using both animal models and longitudinal studies in large patient cohorts is vital for the formulation of effective COVID-19 vaccines and treatments, the authors say.

Some, if not all, early sharks that lived 300 to 400 million years ago not only dropped their lower jaws downward but rotated them outwards when opening their mouths. This enabled them to make the best of their largest, sharpest and inward-facing teeth when catching prey, paleontologists at the Universities of Zurich and Chicago have now shown using CT scanning and 3D printing.

Many modern sharks have row upon row of formidable sharp teeth that constantly regrow and can easily be seen if their mouths are just slightly opened. But this was not always the case. The teeth in the ancestors of today's cartilaginous fish (chondrichthyan), which include sharks, rays and chimaeras, were replaced more slowly. With mouths closed, the older, smaller and worn out teeth of sharks stood upright on the jaw, while the younger and larger teeth pointed towards the tongue and were thus invisible when the mouth was closed.

Jaw reconstruction thanks to computed tomography

Paleontologists at the University of Zurich, the University of Chicago and the Naturalis Biodiversity Center in Leiden (Netherlands) have now examined the structure and function of this peculiar jaw construction based on a 370-million-year-old chondrichthyan from Morocco. Using computed tomography scans, the researchers were able not only to reconstruct the jaw, but also print it out as a 3D model. This enabled them to simulate and test the jaw's mechanics.

What they discovered in the process was that unlike in humans, the two sides of the lower jaw were not fused in the middle. This enabled the animals to not only drop the jaw halves downward but at the same automatically rotate both outwards. "Through this rotation, the younger, larger and sharper teeth, which usually pointed toward the inside of the mouth, were brought into an upright position. This made it easier for animals to impale their prey," explains first author Linda Frey. "Through an inward rotation, the teeth then pushed the prey deeper into the buccal space when the jaws closed."

Jaw joint widespread in the Paleozoic era

This mechanism not only made sure the larger, inward-facing teeth were used, but also enabled the animals to engage in what is known as suction-feeding. "In combination with the outward movement, the opening of the jaws causes sea water to rush into the oral cavity, while closing them results in a mechanical pull that entraps and immobilizes the prey."

Since cartilaginous skeletons are barely mineralized and generally not that well preserved as fossils, this jaw construction has evaded researchers for a long time. "The excellently preserved fossil we've examined is a unique specimen," says UZH paleontologist and last author Christian Klug. He and his team believe that the described type of jaw joint played an important role in the Paleozoic era. With increasingly frequent tooth replacement, however, it became obsolete over time and was replaced by the often peculiar and more complex jaws of modern-day sharks and rays.

CHAPEL HILL, NC--Cutaneous angiosarcoma is a rare, highly aggressive skin tumor found primarily on the scalps of older White people, but based on new research from the University of North Carolina School of Medicine and the Lineberger Comprehensive Cancer Center, immunotherapies effective against lung cancer and melanoma may also work against this cancer. The study's findings are published in the American Journal of Dermatopathology.

The investigators found that two markers that could help guide the choice of immunotherapy to fight this disease: tumor-infiltrating lymphocytes (TILs), which are white blood cells that can kill cancer cells, and surface protein markers, known as PD-1 and PD-L1. Combined, these markers are enabling researcher's efforts in clinical trials for cutaneous angiosarcomas.

"Current treatments for cutaneous angiosarcomas incorporate surgery, radiation and chemotherapy, but are not overly effective," said Paul Googe, MD, a professor in the UNC School of Medicine Dermatology Department and lead author. "Most skin cancers regress in response to inflammation and since immunotherapies that provoke an inflammatory response have proven successful in melanoma, immunotherapies targeted at non-melanoma skin cancers, such as angiosarcomas, also now show promise."

This research was possible due to the efforts of teams of UNC scientists from different fields working together. "It is a big advantage for pushing forward research to have inter-departmental collaboration as seen with this study," said UNC Lineberger's Nancy E. Thomas, MD, PhD, chair of the Dermatology Department at the UNC School of Medicine. "This project required true team science, with investigators bringing complementary and integrated expertise to the project."

"Cutaneous angiosarcomas can be advanced at diagnosis, so treatment is usually multidisciplinary, involving dermatologists, surgical oncologists, radiation therapists and oncologists," said Googe. "Dermatology experts have been invaluable in helping identify patients for a clinical trial and dermatologic follow-up should be helpful in assessing response to therapy."

In this study, the researchers sampled tumor tissue from five men and five women between the ages of 59 and 82 who were newly diagnosed with cutaneous angiosarcoma. They looked at patient tissue samples for the presence of TILs as well as surface proteins PD-1 or PD-L1, which can act as immune checkpoints. Immunotherapy drugs can block PD-1, thereby releasing the brakes on the immune system so that it can attack cancer cells.

In their investigation, all 10 of the patient tumor samples were positive for PD-L1; seven of the tumors expressed PD-L1 at high levels. TILs were all found in all 10 tumors, and more specifically were found at the edge of the tumor and widely comingled with tumor cells in seven of the tumors, indicating a higher likelihood of immune-effectiveness against the cancer.

There have been some individual case reports of success using immunotherapy agents such as pembrolizumab, a PD-1 inhibitor, against cutaneous angiosarcomas. In this study, four of the people showed benefit from pembrolizumab.

"This study is a wonderful example of the bedside to bench, back to bedside," said UNC Lineberger's Juneko Grilley-Olson, MD, an associate professor of medicine at the UNC School of Medicine's Division of Oncology and final author on the article. "Trials in a rare disease require broad-reaching cooperative efforts, and through an extensive network of trial sites supported by the National Cancer Institute, we are bringing our next trial to where patients are, and ask the question of drug effectiveness in the most rigorous scientific way."

The phase II trial, run through the NCI-sponsored Alliance for Clinical Trials in Oncology network, is looking to enroll as many as 90 patients with angiosarcoma to fully evaluate genetic and other abnormalities in the disease. For the first time in this cancer, investigators will try to determine how responsive the disease might be to immunotherapy in combination with conventional chemotherapy, noted Grilley-Olson.

For their research, the researchers have obtained data on 25 patients from organizations such as Eurordis, the Spanish Rare Diseases Federation (FEDER) and the Rare Diseases Patients' Association of Iran with the goal of including testimonials from different territories with different health systems.

The term used to refer to formal representations of knowledge that establish the different concepts of a specific field and the relationships between them is ontology. In such representations, it is important to use an open-source data format and international standards in order to ensure that this representation is accessible in all spheres. The ontology performed by the UOC uses an open source code and is based on standards defined by the World Health Organization (WHO).

A tool for understanding patients that goes beyond treatments

The research is described in the article "Biomedical Holistic Ontology for Patients With Rare Diseases", published in the International Journal of Environmental Research and Public Health. Lead researcher Laia Subirats explained that its value lies in "the fact that a single ontology integrates not just medical information but also information about other aspects that affect patients' lives, such as environmental, geographical and psychological factors, their social relations and their interests. It also includes information taken from Twitter, which gives us social data. The end result is an improved understanding of the patient and access to new data about the patient's interaction with the disease. Viewed in this light, we can say that it is a holistic ontology". Subirats is a course instructor at the UOC's Faculty of Computer Science, Multimedia and Telecommunications, a collaborator with the University's Applied Data Science Lab (ADaS Lab) and a researcher at Eurecat. In 2018, she was included in the list of the 100 most influential women in Spain, in the Top 100 Female Leaders awards.

One of the shortcomings of the ontologies used for rare diseases is that they provide information about the patients separately, without including all the necessary information in a single tool. The ontology developed by the UOC researchers overcomes this shortcoming and provides a useful tool for health professionals, patients and other healthcare stakeholders.

As one of the other members of this research team, Jordi Conesa, who also teaches at the Faculty of Computer Science, Multimedia and Telecommunications and is a researcher with the UOC's SmartLearn group, explained: "We know that medical and genetic information ontologies must be integrated in order to perform personalized translational analyses for each patient. However, we have taken this a step further, as we believe that it is necessary to create holistic ontologies that also contain data about other significant factors affecting patients, including psychosocial, demographic, geographical, and time- and social relations-related information. Health - and the available treatments - is not just something that exists within the confines of our bodies; it is also influenced by the environment. With this ontology, we can now include the environment, and also other factors that impact on the quality and intensity of potential treatments."

Psychologist and researcher Manuel Armayones has also taken part in this research. A member of the UOC's eHealth Center, the Psychology, Health and Network (PSiNET) research group and the Faculty of Psychology and Education Sciences, Armayones considered that it was "very significant that data from patients' associations have been taken into account, as they are usually the health system's least-used resource. If there is one field where data from all possible sources should be considered, it is the rare diseases and, especially, the ultrarare diseases".

No matter how soft and cozy, beds that have gone up in flames are a source of some of the deadliest fires in the U.S. As large pieces of furniture loaded with combustible cushioning materials, beds are substantial fuel sources for home fires. Once ignited, mattress fires can grow quickly, creating life-threatening situations in bedrooms or entire houses within minutes.

A 2007 standard for mattress flammability from the Consumer Product Safety Commission (CPSC), known as 16 CFR Part 1633, sought to curb the danger of bed fires sparked by flames, which caused an estimated 95 deaths annually from 2002-2005. But because of how infrequently consumers replace mattresses, the researchers who helped to develop the standard spent years in the dark about whether the safety requirements were living up to expectations.

Now, enough data has accumulated for researchers at the National Institute of Standards and Technology (NIST) to estimate that the standard prevented 65 deaths from bed fires annually in 2015 and 2016. That number is expected to rise as more mattresses are replaced with the newer, standard-compliant models.

"What we've got here is a clear case of fire researchers, manufacturers and regulators all working together, getting the science right, getting commercially acceptable versions of the mattresses right and getting the regulation right," said NIST research scientist Richard Gann. "It all came together, and as a result we have a real success story for the country."

Long before 2007, other standards were in place to crack down on a leading cause of bed fires in cigarettes, but they left the grave threat of flaming ignition sources, like lighters, matches or pieces of burning furniture, largely unaddressed.

To close that gap, the International Sleep Products Association (ISPA) -- the trade association for the mattress industry -- approached NIST about laying the groundwork for a new mattress flammability standard that would eliminate, or at least greatly reduce, the casualties from bed fires.

Gann and his colleagues leapt at the opportunity and set out to devise a realistic and practical way for manufacturers to test mattress flammability.

Since bed fires typically start with the ignition of blankets, sheets and other bedclothing items, the researchers aimed to replicate the danger they posed to mattresses. Gann and his team assembled several sets of bedclothes, set them ablaze and gauged the heat release rate (HRR) -- an indicator of how intensely something burns, measured in watts -- of each.

They used the HRR data to create a special test apparatus composed of twin propane burners that could mimic fires generated by an off-the-shelf set of bedclothes. With the burners, manufacturers could test their mattresses against conditions similar to real-world bedroom fires.

While the researchers developed this new test method, manufacturers experimented with fire-resistant fabrics -- such as those used in firefighter uniforms -- and implemented them into prototypes to lower their HRR.

But how much lower would the HRR of a mattress need to be? The limit had to be low enough to ensure that burning mattresses would not spark a "flashover," wherein a fire makes a room so hot that all other combustible items in it -- chairs, clothes, etc. -- suddenly and simultaneously ignite, Gann said.

To find the limit, they measured how much heat it would take to ignite small pieces of material, each representing an item commonly found in bedrooms, such as wooden furniture or softer items like upholstery or curtains. The researchers then burned both prototype and commercially available mattresses, measuring the flow of heat to several spots around the room.

With the two data sets, the team discovered that mattresses with a peak HRR of about 600 kilowatts (kW) or more would produce enough heat to reliably ignite soft materials almost anywhere in an ordinary bedroom. While the commercial king- and twin-sized beds they tested had peak HRRs far above this value, one prototype fared much better.

"The manufacturers made some prototypes and they worked. When they sent them here, we tested them," Gann said. "Four megawatts. One megawatt. And then down to 400 kilowatts for a king-size bed. In the world of fire safety, that's a game changer."

When mattresses burn below 400 kW, the odds of flashover decrease substantially, the researchers found. To prevent mattresses from coming close to this threshold, the CPSC's standard requires that mattresses maintain an HRR under 200 kW after being ignited by the burning-bedclothes-simulating burners.

By the time the standard became effective on July 1, 2007, mattresses that met the new requirements were widely available. But did this change actually translate into lives saved? If so, how many lives was it saving? Gann was eager to know, but when he set out two years later to find the answers, he learned that there was a colossal roadblock in the way.

Mattresses remain with their original owners for 10 to 12 years on average. And after that, they are often passed on to children or get refurbished and find a new life back on the market, Gann said. This meant it would take years before enough standard-compliant mattresses found their way into homes. With so little data available at the time, Gann had to wait this one out.

Returning to the issue 10 years later, now with a wealth of information available about fire incidents (fires, injuries and deaths) from the National Fire Incident Reporting System and mattress sales from ISPA, Gann brought aboard NIST economists Stanley Gilbert and Dave Butry, who have developed statistical methods to finally put numbers to the standard's effects.

One of their approaches was to compare the total number of incidents caused by bed fires in 2005 and 2006 combined to the number in 2015 and 2016. They didn't just look at the raw values, though. If other fire-influencing factors -- like the number of homes with smoke alarms -- were not identical between the two time periods, the comparison could be unfair.

To isolate the effect of the standard from other factors, Gilbert and Butry compared the outcomes of bed fires to upholstered furniture fires, as the combustible materials in both types of fires are similar. Because the standard is exclusively about mattresses, any spike or dip that only appeared in the bed fire numbers, but not upholstered furniture fires, would probably have been driven by the standard.

The researchers crunched the numbers and were pleased to identify several strong indicators suggesting that the standard was doing its job and doing it well.
They found that, relative to upholstered furniture fires, the number of bed fires from 2015 and 2016 combined was 12% lower than in 2005 and 2006. In those 10 years, injuries decreased by 34% and, much to the delight of the researchers, deaths plummeted by 82%.

Evidence mounted further in support of the standard as the researchers examined the mattress sales data alongside fire incidents.

The researchers used the sales data to create mathematical models that could estimate how many pre-standard mattresses were being replaced with new ones. The models point to the standard as the likely source of the benefits, as the mattress replacements and reductions in casualties closely mirrored each other throughout the years.

"We used several different approaches to look at the data, and they all pointed to the same conclusion; the standard saves lives," Gilbert said.

Ryan Trainer, president of ISPA, which was involved in developing and implementing 16 CFR Part 1633, also voiced appreciation that the standard has borne fruit.

"The mattress industry has collaborated with NIST and CPSC to develop a standard that is based on sound science, reflects real world risks, improves safety and is practical for manufacturers to adopt," Trainer said. "We are gratified that NIST's analysis of national fire statistics shows that since Part 1633 was implemented, the number of bed fires ignited by open-flame heat sources, and especially the deaths and injuries from those fires, have dropped so significantly."

In a study of women aged 80 years and older, living in locations with higher exposures to air pollution was associated with increased depressive symptoms. The findings are published in the Journal of the American Geriatrics Society.

When looking at individual air pollutants, a team led by investigators from of the University of Southern California found that long-term exposure to nitrogen dioxide or fine particulate air pollution was associated with increased depressive symptoms, but with only a small effect. Results also suggested that depressive symptoms might play a role in linking long-term air pollution exposure to memory decline more than 10 years after the exposure.

"This is the first study showing how air pollution exposures affect depressive symptoms as well as the interrelationship between the symptoms and subsequent memory decline that had not been found in older people aged less than 80 years," said lead author Andrew Petkus, PhD.

Senior author Jiu-Chiuan Chen, MD, ScD, added, "We know late-life exposures to ambient air pollutants accelerate brain aging and increase the dementia risk, but our new findings suggest the oldest-old populations may respond to air pollution neurotoxicity in a different way that needs to be investigated further."

An article published in Bioethics examines the topic of research fatigue--or psychological and emotional exhaustion both towards and as a result of participating in research. The article is meant to initiate a conversation about research fatigue experienced by marginalized communities and how the research community should respond to it.

As global interconnectivity facilitates an increasing amount of research and studies on hard-to-reach communities, research fatigue is likely to grow. Analyzing and addressing the ethical aspects of research fatigue can help mitigate its impacts on marginalized and vulnerable communities and on the quality of scientific research itself.

Research fatigue in marginalized communities is a systemic issue that requires systemic responses, noted the article's author, Florence Ashley, of the University of Toronto. "No one wants to be the reason why their colleague can't recruit enough participants for their study. No one wants to be the reason why studies that would promote social justice don't get completed, and thereby contribute to ongoing inequalities," they said. "Researchers and research ethics committees should ensure that studies are responsive to the needs of the researched community and tailored in all ways to minimize research fatigue."

A study published in Ecological Applications suggests that nature around one's home may help mitigate some of the negative mental health effects of the COVID-19 pandemic.

An online questionnaire survey completed by 3,000 adults in in Tokyo, Japan, quantified the link between five mental-health outcomes (depression, life satisfaction, subjective happiness, self-esteem, and loneliness) and two measures of nature experiences (frequency of greenspace use and green view through windows from home).

More frequent greenspace use and the existence of green window views from the home were associated with increased levels of self-esteem, life satisfaction, and subjective happiness, as well as decreased levels of depression and loneliness.

"Our results suggest that nearby nature can serve as a buffer in decreasing the adverse impacts of a very stressful event on humans," said lead author Masashi Soga, PhD, of The University of Tokyo. "Protecting natural environments in urban areas is important not only for the conservation of biodiversity, but also for the protection of human health."

Food allergies are a big problem. About 7% of children and 2% of adults in the U.S. suffer from some kind of food allergy. These allergies cost a whopping $25 billion in health care each year. Then there's the time lost at school or work. And there's the risk of serious complications, even death.

It's critical to find ways to reduce the suffering caused by food allergies. Food processing companies already spend a lot of effort to label products so people can avoid items they're allergic to. But what if we could do better? What if we could enjoy the foods we like without worrying they might trigger a health crisis?

That's the focus of Eliot Herman's work. Herman has spent his career studying why plants trigger allergic reactions and how to reduce the chance of them being triggered. Herman is a member of the Crop Science Society of America and recently presented his work at the virtual 2020 ASA-CSSA-SSSA Annual Meeting.

"Food allergies are an important societal issue. By altering food and by treating sensitive individuals, this can be mitigated, improving their lives and impacting the total medical expenditure in the U.S.," says Herman.

Herman focuses particularly on soybeans. Soybean allergies especially affect children and infants. And because soybean products like oil and protein are used in countless food products, it's hard to avoid.

Earlier in his career, Herman found the protein made by soybeans that is responsible for most soybean allergies. Now, he has dedicated his work to understanding why this protein is so aggravating and how we can reduce it in the crop.

To do so, he's turning to animal models. Pigs sometimes have a soybean allergy very similar to that of humans. Herman worked with a research team that bred pigs that are extra sensitive to soybeans. Testing new crops on allergic children wouldn't be possible. But these pigs can be used to see how well plant breeders have done at removing allergenic proteins from soybean seeds.

That's a feat that Herman has done not once, but twice. Previously, Herman partnered with the company DuPont to produce a line of soybeans that couldn't make the most allergenic protein.

They made this soybean line using genetic engineering. This new soybean was a genetically modified organism (GMO), and there was also demand for a non-GMO soybean without the allergenic protein.

So Herman went back to the drawing board. He worked with his colleagues to find a line from the United States Department of Agriculture's (USDA) national soybean collection that naturally didn't make the allergenic protein. That means no genetic engineering would be necessary. They then crossed that line of soybeans with a more commonly grown soybeans to create a new, productive soybean with reduced allergic sensitivity.

"This new soybean is intended to be a low-allergen prototype to be tested as a conventional, non-GMO line to mitigate the allergic response for consumers," says Herman.

The hypersensitive pigs can now be used to test if these low-allergen soybeans are safe enough for allergic individuals. That wouldn't only be good for allergic people who want to safely eat more items from the grocery store. It would also be good news for animals.

Since pigs are often fed soybeans, a low-allergen soybean could reduce their own allergic response. Dogs also have a high prevalence of allergic reactions to soybean, which is used in some dog foods. So reducing the crop's allergenicity would be good for man's best friend, too.

"Food has been recognized as medicine since ancient times. By reducing soybean's allergens, we hope to produce positive a medical outcome for humans and animals," says Herman.

Surgeons' preoperative expectations were more accurate than patients' expectations in predicting patient-reported outcomes two years after lumbar spine surgery, according to a longitudinal study by investigators at Hospital for Special Surgery (HSS). Most patients had higher expectations than their surgeons did, with many anticipating complete improvement after seeking additional information beyond that provided by their surgeons.

Lower back pain is complex, requiring accurate diagnosis and careful consideration of treatment options. Mechanical problems, such as a muscle strain from heavy lifting or twisting, a sudden jolt in a car accident, a herniated disc from stress on spinal bones or joint degeneration due to osteoarthritis, are typical causes of lower back pain. Most patients do not require surgery and are treated with medications to relieve pain and reduce inflammation. Surgical options are considered for back pain that does not respond to other therapies.

"There have been tremendous advances in spine surgery over the past 20 years, including minimally invasive and robotic approaches, new implants and bone grafting methods," says Federico P. Girardi, MD, an attending orthopaedic surgeon at HSS. "However, despite clinical assessment and improvements seen on postoperative imaging, some patients report they are not doing well compared to others with similar conditions who received the same surgeries. That has been very frustrating for surgeons because our goal is to optimize patient outcomes."

"Patients decide to pursue lumbar spine surgery to relieve symptoms, improve their quality of life and avoid further disability," says Carol A. Mancuso, MD, FACP, a general internist and clinical epidemiologist at HSS. "Unrealistically high or low expectations are problematic, predisposing patients to poor outcomes if they become discouraged with recovery, abandon rehabilitation or ignore recommended lifestyle modifications that reduce disease progression."

To understand the gap between expectations and patient-reported outcomes, Dr. Girardi, Dr. Mancuso and colleagues developed the HSS Lumbar Spine Surgery Expectations Survey in 2013 with input from hundreds of patients on the surgical outcome factors that matter most to them. The comprehensive, validated tool evaluates patients' expectations for symptom relief, resuming activities, and importantly, psychological well-being, which previous surgeon-oriented surveys did not capture. The HSS Lumbar Spine Surgery Expectations Survey is one of several patient-centered tools developed by Dr. Mancuso and HSS researchers used worldwide and considered the gold standard for measuring patients' expectations with orthopedic surgery.

For their recent study, published online ahead of print on November 4, 2020 in the journal Spine, Dr. Girardi, Dr. Mancuso and colleagues asked 402 patients and their surgeons to preoperatively assess their expectations of patient-reported surgical outcomes using the HSS Lumbar Spine Surgery Expectations Survey. The researchers surveyed patients again, two years after surgery, to evaluate the degree of fulfillment of their expectations.

Patients participating in the study were 55 years of age, on average. Most had a degenerative spine condition and had experienced symptoms for a year or longer. About one-quarter had undergone previous spine surgery, and one-third were taking opioids to relieve leg and back pain. The extent of surgical procedures spanned from the removal of a single, herniated disc to more complex operations such as a five-level anterior-posterior decompression, instrumentation and fusion.

Responses to the HSS Lumbar Spine Surgery Expectations Survey generate a score on a scale of 0 to 100, where a higher score indicates higher expectations. Patients' average preoperative score in the study was 73 (ranging from 20 to 100), much higher than surgeons' average score of 57 (ranging from 16 to 100).

Next, the investigators determined whether surgeons or patients' presurgical expectations more closely predicted postoperative fulfillment of those expectations as reported by patients. The proportion of expectations fulfilled was .79 for patients, indicating that they were satisfied overall. Dr. Mancuso's previous research found that a ratio of .6 or higher corresponds with satisfaction with surgical results. However, the surgeons' ratio was 1.01, meaning that their predictions for patient-reported outcomes were highly accurate and more accurate than patients' presurgical estimates. In 73 percent of cases, surgeons either predicted patients' reported outcomes exactly, or patients surpassed surgeons' expectations.

"HSS spine surgeons very accurately predicted patient-reported outcomes two years after surgery, indicating that they are adept at integrating complex clinical, surgical and psychological factors that matter most to patients," says Dr. Mancuso. "Getting this right is an indicator of providing high-quality and high-value care."

Overall, surgeons and patients agreed on the same areas of improvement. However, expectations for the degree of improvement differed. Surgeons expected surgery would lead to a little, moderate, or a lot of improvement, based on their clinical expertise treating hundreds of patients. However, 84 percent of patients had higher expectations than their surgeons, often expecting complete improvement. The investigators interviewed patients about the source of their expectations and discovered they had amplified their surgeons' guidance with information they obtained from family, friends, coworkers and the internet.

"Our study underscores that there is room for improvement in patient education and that patients should rely on their surgeon's expertise when forming expectations of lumbar spine surgery," Dr. Girardi says. "At HSS, we recognize that expectations for surgical outcomes are affected by many factors and develop evidence-based, individualized treatment plans. Patients need to realize that anecdotal stories from social contacts or the internet are often not relevant to their situation."

WEST LAFAYETTE, Ind. - Machine learning has been used widely in the chemical sciences for drug design and other processes.

The models that are prospectively tested for new reaction outcomes and used to enhance human understanding to interpret chemical reactivity decisions made by such models are extremely limited.

Purdue University innovators have introduced chemical reactivity flowcharts to help chemists interpret reaction outcomes using statistically robust machine learning models trained on a small number of reactions. The work is published in Organic Letters.

"Developing new and fast reactions is essential for chemical library design in drug discovery," said Gaurav Chopra, an assistant professor of analytical and physical chemistry in Purdue's College of Science. "We have developed a new, fast and one-pot multicomponent reaction (MCR) of N-sulfonylimines that was used as a representative case for generating training data for machine learning models, predicting reaction outcomes and testing new reactions in a blind prospective manner.

"We expect this work to pave the way in changing the current paradigm by developing accurate, human understandable machine learning models to interpret reaction outcomes that will augment the creativity and efficiency of human chemists to discover new chemical reactions and enhance organic and process chemistry pipelines."

Chopra said the Purdue team's human-interpretable machine learning approach, introduced as chemical reactivity flowcharts, can be extended to explore the reactivity of any MCR or any chemical reaction. It does not need large-scale robotics since these methods can be used by the chemists while doing reaction screening in their laboratories.

"We provide the first report of a framework to combine fast synthetic chemistry experiments and quantum chemical calculations for understanding reaction mechanism and human-interpretable statistically robust machine learning models to identify chemical patterns for predicting and experimentally testing heterogeneous reactivity of N-sulfonylimines," Chopra said.

This work aligns with other innovations and research from Chopra's labs, whose team members work with the Purdue Research Foundation Office of Technology Commercialization to patent numerous technologies. To find out more information about their patented inventions, contact otcip@prf.org.

"The unprecedented use of a machine learning model in generating chemical reactivity flowcharts helped us to understand the reactivity of traditionally used different N-sulfonylimines in MCRs," said Krupal Jethava, a postdoctoral fellow in Chopra's laboratory, who co-authored the work. "We believe that working hand-to-hand with organic and computational chemists will open up a new avenue for solving complex chemical reactivity problems for other reactions in the future."

Chopra said the Purdue researchers hope their work will pave the way to become one of many examples that will showcase the power of machine learning for new synthetic methodology development for drug design and beyond in the future.

"In this work, we strived to ensure that our machine learning model can be easily understood by chemists not well versed in this field," said Jonathan Fine, a former Purdue graduate student, who co-authored the work. "We believe that these models have the ability not only be used to predict reactions but also be used to better understand when a given reaction will occur. To demonstrate this, we used our model to guide additional substrates to test whether a reaction will occur."