Culture

UCLA RESEARCH BRIEF

FINDINGS

UCLA researchers have identified a potential diagnostic marker that could help predict how likely someone with cervical cancer is to respond to the standard treatment of chemotherapy and radiation.

The scientists found that PACS-1, a gene that resides on a small segment of the long arm of chromosome 11, is overexpressed in cancer tissues, which can result in cancer growth and spread. Further, they discovered that translocation of the PACS-1 protein from outside to inside the cell nucleus -- a function required for normal cell growth -- plays a role in the development of cervical cancer that is resistant to chemotherapy and radiation. Higher levels of PACS-1 expression in the nucleus could indicate resistance to the treatment, the researchers say.

BACKGROUND

Cervical cancer is the second leading cause of cancer-related death among women worldwide. While infection with human papillomaviruses plays a significant role in cervical cancer development, the presence of a virus alone is not enough to cause cancer; genetics and environmental factors such as smoking and poor eating habits also play a role. Therefore, it is important to identify biological markers as targeting agents for diagnosis and treatment.

METHOD

The researchers performed a western blot, a technique for detecting specific protein molecules from among a mixture of proteins, on cervical tumors and healthy cervical tissue and discovered an overexpression of PACS-1 in the tumor tissues. The team then developed in vitro human cell line models to assess the protein's role in cell growth. Finally, they used a fluorescence-activated sorter analysis to help determine if the overexpression of PACS-1 protein was associated with cancer chemo resistance.

IMPACT

If confirmed in animal studies, the use of PACS-1 as a diagnostic marker could help lead to the development of therapeutic strategies to overcome treatment resistance in cervical cancer. Alternative methods of treatment, including the inhibition of PACS-1 expression, could be used in combination with chemotherapy or immune system-activating agents.

AUTHORS

The study's senior author is Eri Srivatsan, a professor of surgery at the David Geffen School of Medicine at UCLA and member of UCLA's Jonsson Comprehensive Cancer Center and Molecular Biology Institute. The first author is Mysore Veena, a scientist at the Geffen School of Medicine.

JOURNAL

The study is published online in the Journal of Biological Chemistry.

FUNDING

The research was supported in part by the National Cancer Institute and the Veterans Affairs Greater Los Angeles Healthcare System.

CHICAGO (December 11, 2020): Financial toxicity among breast cancer patients is independently associated with worse psychological well-being following a mastectomy or lumpectomy operation. However, even small improvements in financial pressure associated with treatment-related costs can lead to better mental well-being and higher patient satisfaction with breast reconstruction, according to an "article in press" published on the website of the Journal of the American College of Surgeons ahead of print.

Women undergoing breast cancer surgery are vulnerable to financial stress due to the expensive and extended duration of treatment. High out-of-pocket costs can take a major toll on a patient's health, leading to financial toxicity (the harm or stress a person experiences due to the unaffordability of his or her medical care).

"Breast cancer therapy is highly sensitive to patient preferences, so right from the start patients are expected to make a lot of decisions and each one has trade-offs," said lead study author Christopher J. Coroneos, MD, MSc, an assistant professor of plastic surgery at McMaster University in Ontario, Canada. "There is a unique set of decisions that a patient has to make--undergoing a lumpectomy versus mastectomy, undergoing chemotherapy, adjuvant therapy and radiation, and then breast reconstruction--that is why breast cancer is different from other cancers."

Even so, timely and in-depth discussions between providers and patients about the cost of cancer care are uncommon. This is the first study to examine the connection between financial distress and quality-of-life outcomes (overall and condition specific) in women who undergo surgery for breast cancer, according to the authors.

Researchers analyzed the results of three self-reported surveys and medical record data for 532 women who underwent lumpectomy or mastectomy at The University of Texas MD Anderson Cancer Center in Houston. Patients were aged 18 years and older and had completed the surveys within 18 months of their breast cancer operation. Most of the patients (64 percent) underwent breast reconstruction. The median annual household income was reported between $80,000 and $120,000, well above the national average.

Using the COST (COmprehensive Score for financial Toxicity) questionnaire, researchers identified patients in financial distress. In addition, participants responded to questions from the BREAST-Q and SF-12 surveys, designed to assess quality of life, mental well-being, and physical satisfaction after undergoing breast reconstruction; a lower score represents a worse outcome.

After adjusting for multiple confounding factors, the analysis showed that financial toxicity, as reflected in a lower COST score, was strongly associated with lower BREAST-Q and SF-12 scores, indicating worse outcomes. Further, COST had the largest impact on one particular outcome, psychological well-being, with a one unit increase in COST correlated with a 0.89 unit increase in the psychological well-being score.

"Even a small change in financial toxicity translates to an important change in psychosocial well-being," Dr. Coroneos said. The data also showed a positive relationship between patients' psychological well-being and their own perceived satisfaction with the outcome of their breast reconstruction.

The study builds on previous findings examining the link between financial toxicity and quality of life. However, this study is important because it uses validated patient reported outcome measures for the analysis.

"In this world of patient-centered outcomes and value-based care, there are two takeaway points from our study. First, for populations at high risk for financial toxicity, deliberations around treatment costs are incredibly important. Second, early intervention in instances of self-reported financial toxicity will be a key element of maximizing patient-reported outcomes in breast cancer surgery. This is because financial toxicity really does dampen the high-quality, patient-centered outcomes we are capable of delivering," said study senior author Anaeze C. Offodile II, MD, MPH, an assistant professor of plastic surgery at The University of Texas MD Anderson Cancer Center, Houston.

Currently, the authors are conducting a prospective multi-center trial, reproducing this work in a variety of settings. They hope to get a more in-depth understanding of how economic well-being impacts quality of life outcomes in breast cancer surgery (timing, triggers and duration), and ultimately, how interventions that improve the economic well-being of cancer patients could lead to improvements in care.

"What clinicians have to do with these study results is to consider the financial reserve patients have when discussing breast cancer management." Dr. Coroneos said. "From a research perspective, integrating the financial risk and patient reported outcomes can inform decision-making models, and is especially important in vulnerable populations."

Researchers from The University of Texas at Arlington resurrected the preserved eggs of a shrimp-like crustacean to examine long-standing questions about adaptive evolution, reporting the results in the journal Proceedings of the National Academy of Science.

The study explores the evolutionary impacts of species invasions by studying Daphnia, a shrimp-like crustacean also known as the water flea. Matthew Walsh, associate professor of biology; Alex Landy, UTA postdoctoral researcher; and their colleagues collected sediment cores containing the preserved eggs of Daphnia from lakes in Wisconsin following the invasion of a novel predator. The researchers then "resurrected" the eggs in hopes of seeing novel evolutionary processes in real time.

"Each layer of the sediment core represents a distinct time period and contains a generation of water flea eggs that sank to the lake floor," Walsh said. "By hatching the eggs, we are able to measure the viability and traits of water fleas from before, during and after the invasion of the novel predator."

According to the study, variations in how the ancestors responded to the novel predator were central to water flea adaptation. Yet few studies have been able to assess the characteristics of ancestral populations prior to a change in the environment, Walsh said.

"The key advance illustrated by our work is that the resurrected ancestral lineages of Daphnia revealed extensive genetic variation in their responses to exposure to a novel predator," Walsh said. "Such variation in plasticity provided a template for evolution to proceed following the establishment of the predator."

Walsh added that his team's work is important because it allows researchers to observe evolutionary processes in real time to better understand how organisms adapt to changes in environmental conditions, such as rising temperatures, habitat loss or species invasions.

"Our results highlight the importance of quantifying genetic variation in plasticity when evaluating the drivers of evolutionary change in the wild," Walsh said. "Furthermore, our work calls for more studies that quantify genetic variation in ancestral populations to better understand how and why evolution occurs in a natural setting."

WHAT:

The combination of baricitinib, an anti-inflammatory drug, and remdesivir, an antiviral, reduced time to recovery for people hospitalized with COVID-19, according to clinical trial results published in the New England Journal of Medicine. The study was supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

The clinical trial is the second iteration of the NIH Adaptive COVID-19 Treatment Trial (ACTT-2), a study protocol to evaluate therapeutics for people hospitalized with COVID-19. Remdesivir is a broad-spectrum antiviral treatment developed by Gilead Sciences, Inc. Baricitinib was discovered by Incyte and licensed to Eli Lilly and Company, and marketed under the brand name Olumiant. It is approved in more than 70 countries as a treatment for adults with moderately-to-severely active rheumatoid arthritis. Researchers hypothesized that because many severe symptoms of COVID-19 are caused by a poorly regulated inflammatory response, a therapeutic designed to target inflammation could be helpful for patients. The primary results of this study were first announced in September.

The ACTT-2 trial opened on May 8, 2020 and enrolled a total of 1,033 volunteer participants at sites in eight countries. Once enrolled, participants were randomized to receive a treatment regimen of either oral baricitinib tablets and intravenous (IV) remdesivir or oral placebo tablets and IV remdesivir.

In the study, the combination of baricitinib and remdesivir reduced median time to recovery in hospitalized COVID-19 patients from eight days to seven days. Patients who required high-flow oxygen or non-invasive ventilation during their hospitalization appeared to have had the largest benefit: their median time to recovery was shortened from 18 days to ten days. In addition, participants' conditions at day 15 of the study (as measured by an eight-category ordinal scale which ranked the severity of their condition) was significantly improved when they received the two therapeutics combined. Recipients of the two treatments also had slightly fewer serious adverse effects.

The researchers caution that comparing this COVID-19 treatment regimen versus those with other therapeutics, such as dexamethasone, is difficult without additional comparison studies. These results do appear to show that baricitinib plus remdesivir can benefit some COVID-19 patients and the combination deserves further clinical study, according to the researchers.

URBANA, Ill. - Smallholder farmers in Sub-Saharan Africa use fertilizer well below recommended rates, contributing to consistently low agricultural productivity. Farmers in Tanzania and Kenya, for example, apply just 13 kilograms of fertilizer per hectare, compared with 165 to 175 kilograms in India and Brazil. Low use directly affects cereal yields, which average 1.2 to 1.7 metric tons per hectare, compared to 4 to 4.5 metric tons in South America and Asia.

A new study from the University of Illinois finds farmers have misconceptions about fertilizer quality and suggests those misconceptions are a major reason for low application rates.

"Farmers were not using much fertilizer; that's well established in the region of Tanzania where we were working. In discussions with farmers we heard again and again the explanation was they thought the fertilizer was fake or bad, and they didn't want to buy it," says Hope Michelson, associate professor in the Department of Agricultural and Consumer Economics (ACE) at U of I.

"I'd heard this in other, similar locations where I'd worked with farmers," Michelson says. "We decided to focus on this question of quality: Is the fertilizer bad?"

Michelson and her colleagues conducted a case study in Tanzania to gain more insight into fertilizer quality and farmers' beliefs and willingness to buy it.

Anna Fairbairn, then-graduate student in ACE and co-author on the study, spent a year collecting data throughout Tanzania's Morogoro Region.

Fairbairn first conducted a census to identify all shops in the region selling fertilizer. She drove with her team along primary and secondary roads for weeks, stopping at any shop that looked like it might sell fertilizer. They interviewed all dealers about their practices and prices. Then, "mystery shoppers" posing as farmers purchased more than 600 fertilizer samples from 225 dealers, recording prices and other details about the transactions. The samples went to laboratories in Kenya and the U.S. for analysis.

The researchers included three types of fertilizer that are important for ag production in Tanzania - urea, calcium ammonium nitrate (CAN), and diammonium phosphate (DAP). The lab results showed just a small percentage of samples were marginally out of compliance with industry standards. They did not indicate widespread evidence of the fraud and quality problems that farmers worried about. These results are consistent with findings from numerous academic studies and from international organizations like the International Fertilizer Development Center conducted in recent years.

"It makes sense that the quality is good. Urea fertilizer is difficult to adulterate, and it is one of the cheapest fertilizers. You would have to dilute it with something even cheaper, and there are not very many options. So it is not likely to happen," Michelson notes.

After the quality analysis, Fairbairn and her assistants interviewed 165 farmers in 12 villages across the region. They set up a "store," where they showed farmers samples of urea - the most prevalent fertilizer for small farmers - and asked how much they would be willing to pay for them.

"We found evidence that farmers worry about the quality of the fertilizer in the marketplace, and that impacts their willingness to pay for it. This can affect the amount of fertilizer they're buying, and whether or not they purchase fertilizer at all," Michelson states.

After the farmers' initial responses, the researcher would tell them that the fertilizer had been lab tested and shown to have adequate nutrition content. This information increased the farmers' willingness to pay by about 50%.

Michelson says there may be several explanations for the farmers' distrust in fertilizer quality.

"These farmers are operating in contexts with weak regulatory systems and may be broadly suspicious. It is interesting and significant to find evidence that farmers' beliefs are not converging to the truth - of good quality fertilizer in the marketplace - over time," she states.

Michelson says farmer distrust could be exacerbated by the difficulty in observing the effect of fertilizer on crop yields.

"You could be applying at the wrong time, or not applying enough. Weather is also a factor driving crop yields. You can't always tell if the fertilizer is doing anything because of the rainfall variability factor. Farmers could blame these things on the fertilizer not being good quality," she says.

An important factor that may influence the beliefs the researchers identified is the appearance of the fertilizer. "We find evidence there is an enormous problem with fertilizer in the marketplace that looks bad. It may be dirty or have clumps, sticks, and small amounts of impurities in it," Michelson notes. "More than 30% of the samples we purchased had this sort of problem."

Wholesalers import urea through the port of Dar es Salaam, where it gets bagged and transported into the country. Inadequate storage facilities and transportation resources can result in a compromised appearance that has no bearing on quality and effectiveness.

The research confirmed that farmers were willing to pay less for fertilizer with this poor physical appearance.

For smallholder farmers, purchasing fertilizer is a substantial expense, amounting to about 10% of annual per capita income in the household. It's a non-trivial investment that comes with a measure of risk. And they are not willing to make that investment if they do not believe it will be worth the cost, Michelson notes.

The researchers conclude misconceptions about fertilizer quality could severely hamper crop productivity in developing countries, and additional research can help further explore those correlations and the persistence of these misconceptions in the marketplace.

CHAPEL HILL, NC - It's been shown that when two people wearing masks interact, the chance of COVID-19 transmission is drastically reduced. This is why public health officials have pleaded for all people to wear masks: they not only protect the wearer from expelling particles that might carry SARS-CoV-2, the virus that causes coronavirus 2019 (COVID-19), but masks also protect the wearer from inhaling particles that carry the virus. Some people, though, still refuse to wear a mask. So UNC School of Medicine scientists, in collaboration with the Environmental Protection Agency, researched the protectiveness of various kinds of consumer-grade and modified masks, assuming the mask wearer was exposed to the virus, like when we interact with an unmasked infected person.

Published in the journal JAMA Internal Medicine, the research shows that some masks were as much as 79 percent effective at blocking particles that could carry the virus. These were masks made of two layers of woven nylon and fit snug against the wearer's face. Unmodified medical procedure masks with ear loops - also known as surgical masks - offered 38.5 percent filtration efficacy, but when the ear loops were tied in a specific way to tighten the fit, the efficacy improved to 60.3 percent. And when a layer of nylon was added, these masks offered 80 percent effectiveness.

"While modifications to surgical masks can enhance the filtering capabilities and reduce inhalation of airborne particles by improving the fit of the mask, we demonstrated that the fitted filtration efficiencies of many consumer-grade masks were nearly equivalent to or better than surgical masks," said co-first author Phillip Clapp, PhD, an inhalation toxicologist and assistant professor of pediatrics at the UNC School of Medicine.

Co-first author Emily Sickbert-Bennett, PhD, director of infection prevention at the UNC Medical Center, added, "Limiting the amount of virus is important because the more viral particles we're exposed to, the more likely it is we will get sick and potentially severely ill."

As the adoption of face coverings during the COVID-19 pandemic became commonplace, there was a rapid expansion in the public use of commercial, home-made, and improvised masks which vary considerably in design, material, and construction. There have been a number of innovative "hacks," devices, and mask enhancements that claim to improve the performance characteristics of conventional masks - typically surgical or procedure masks. Despite their widespread dissemination and use during the pandemic, there have been few evaluations of the efficiency of these face coverings or mask enhancements at filtering airborne particles.

In this study, the researchers used a recently described methodological approach based on the OSHA Fit Test to determine the fitted filtration efficiency (FFE) of a variety of consumer-grade and improvised facemasks, as well as several popular modifications of medical procedure masks. Seven consumer-grade masks and five medical procedure mask modifications were fitted on an adult male, and FFE measurements were collected during a series of repeated movements of the torso, head, and facial muscles as outlined by the OSHA Quantitative Fit Testing Protocol.

Here are the different mask types with filtration efficacy. Bolded below is the top-of-the-line N-95 mask, which proved to be 98 percent effective.

Consumer-grade facemasks:

2-layer woven nylon mask, ear loops, w/o aluminum nose bridge: 44.7%
2-layer woven nylon mask, ear loops, w/ aluminum nose bridge: 56.7%
2-layer woven nylon mask, ear loops, w/ nose bridge, 1 non-woven insert: 74.4%
2-later woven nylon mask, ear loops, w/ nose bridge, washed, no insert: 79%
Cotton bandana - folded Surgeon General style: 50%
Cotton bandana - folded "Bandit" style: 49 %
Single-layer woven polyester gaiter/neck cover (balaclava bandana): 37.8%
Single-layer woven polyester/nylon mask with ties: 39.7%
Non-woven polypropylene mask with fixed ear loops: 28.6%
Three-layer woven cotton mask with ear loops: 26.5%

Medical facemasks and modifications:

3M 9210 NIOSH-approved N95 Respirator: 98%
Surgical mask with ties: 71.4%
Procedure mask with ear loops: 38.5%
Procedure mask with ear loops + "loops tied and corners tucked in": 60.3%
Procedure mask with ear loops + "Ear Guard": 61.7%
Procedure mask with ear loops + "23mm claw hair clip": 64.8%
Procedure mask with ear loops + "Fix-the Mask (3 rubber bands)": 78.2%
Procedure mask with ear loops + "nylon hosiery sleeve": 80.2%

Offering an ultrasensitive yet accessible approach to COVID-19 testing, a portable saliva-based smartphone platform provides results within 15 minutes without the resource-intensive laboratory tests the current gold standard requires, according to a new study. The approach was tested in 12 people infected with COVID-19 and 6 healthy controls. Bo Ning and colleagues demonstrate that this technique, which pairs a fluorescence microscope readout device with a smartphone to determine viral load from a CRISPR/Cas12a assay, works as effectively as the well-established quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR) method. "We believe this smartphone platform, a similar future application, offers the potential to rapidly expand COVID-19 screening capacity, and potentially simplify the verification of contact tracing, to improve local containment and inform regional disease control efforts," the authors write. Most COVID-19 tests currently require swabbing the upper part of the throat behind the nose - an uncomfortable process that requires medical professionals in full protective gear to collect samples in airborne infection isolation rooms before running RT-qPCR tests. However, recent studies have found that SARS-CoV-2 may be equally present in the nasopharynx and the saliva during early infection, suggesting saliva-based COVID-19 tests could enable comparably reliable but simpler, safer testing. To develop a widely accessible platform for saliva-based testing, Ning and colleagues built a prototype assay chip that uses the CRISPR/Cas12a enzyme to enhance an amplified viral RNA target's signal within a saliva sample. They integrated the chip into a smartphone-based fluorescence microscope readout device, which captures and analyzes images to determine whether the virus is present above a threshold concentration. The researchers used this design to analyze saliva from 12 patients with COVID-19 and 6 healthy controls, finding that the approach successfully distinguished between patients with and without the virus. Additionally, the researchers compared nasal and saliva swabs from non-human primates before and after infection. They found higher SARS-CoV-2 RNA levels in the saliva swabs, further suggesting that saliva may provide a robust means of diagnosis after infection. Ning et al. anticipate that a future version of the chip used in this technique could contain pre-loaded reagents and sample controls, and a custom smartphone app could enable secure, wireless test data reporting to support telehealth efforts.

In the United States, political partisanship has played a much stronger role in individuals' decisions to limit their social mobility during the COVID-19 pandemic than the local incidence of the disease in their own communities, according to a new survey-based study of 1,135,638 million responses collected between April 4 and September 10, 2020 via Survey Monkey from randomly chosen people. The analysis, based on an average of 6,744 responses daily during the study period, suggests partisanship has been roughly 27 times more important than local COVID-19 prevalence for explaining individual mobility. In addition, Joshua Clinton and colleagues also found that self-identified Democrats were 13.1% less likely to be socially mobile compared with independents, while Republicans were 27.8% more likely to be mobile. Notably, this gulf widened over time, driven largely by increasing unwillingness on the part of self-identified Republicans to limit their mobility. The researchers weighted each day's sample cohort to be representative of the country's adult population using current estimates from the U.S. Census Bureau's American Community Survey. Each survey asked respondents to identify their political affiliation (Democrat, Republican, or Independent) and to report whether, in the preceding 24 hours, they had engaged in activities such as going to a restaurant, visiting family or friends, taking a walk, exercising, getting groceries, receiving medical care, or going to work. While the analysis primarily focused on the daily aggregate of all such activities, the researchers also found similar trends among individual activities as well, and further noted that the gap was even more pronounced when looking at riskier, voluntary activities such as eating at a restaurant or visiting with family or friends. "These differences have tremendous consequences for the ability of the United States to limit the spread of COVID-19," the authors write, further noting that their results "add to a growing consensus that partisanship is a key factor in explaining behavior and attitudes surrounding the COVID-19 pandemic."

BOSTON - "Wet" age-related macular degeneration (AMD) is one of the most common causes of irreversible vision loss in the elderly, and it occurs when abnormal and leaky blood vessels form in the retina, in part due to inflammation. New research by investigators at Massachusetts General Hospital (MGH) reveals insights into potential drivers of the disease -- which currently has no cure -- that could be targeted through prevention or treatment strategies. The findings are published in eLife.

Two inflammatory pathways involving complement (which is an immune system component) and a protein complex called the inflammasome (which, as its name suggests, triggers inflammation) promote the formation of abnormal blood vessels that are hallmarks of wet AMD, but it's unclear how these pathways are activated. Previous studies suggest that the inflammasome may be activated by a protein called NLRP3, mainly in the retinal pigment epithelium of the eye (a cell layer that separates the vascular layer of the eye from the retina).

To investigate further, researchers conducted experiments in a mouse model of wet AMD. The team showed that inflammasome activation by NLRP3 occurs mainly in cells called macrophages and microglia, but not in the retinal pigment epithelium. The scientists also discovered that proteins other than NLRP3 can lead to inflammasome activation and worsening of wet AMD.

"This means that rather than targeting only NLRP3 in wet AMD, it may be beneficial to block essential proteins of the inflammasome instead that are required for its activation, independently of whether NLRP3 or other proteins initiate inflammasome activation," explains senior author Alexander G. Marneros, MD, PhD, a principal investigator at MGH's Cutaneous Biology Research Center and an associate professor of Dermatology at Harvard Medical School. "Our findings provide guidance on how to block inflammasomes in wet AMD."

Marneros notes that previous studies conducted in cells suggest that complement activation can in turn lead to inflammasome activation, but this study in mice found that this activation occurs largely independently from complement-mediated inflammation. "Our study in a mouse model defines the cell types that contribute to inflammasome-mediated inflammation in wet AMD and uncovers the specific roles and contributions of NLRP3 inflammasomes, non-NLRP3-inflammasomes, and complement for the manifestation of wet AMD," he says.

In addition to providing new insights into how inflammation is regulated in wet AMD, the study also suggests that novel therapies that block inflammasome-mediated inflammation could be improved when combined with treatments that inhibit complement-mediated inflammation. "A combined therapeutic approach that blocks both these inflammatory pathways is likely going to have synergistic effects in lessening the symptoms of wet AMD. Thus, our findings in this mouse model may have important clinical relevance for novel therapies for this common blinding disease," says Marneros.

People in European countries with the strictest COVID-19 lockdown policies were more likely to show symptoms of depression and anxiety, according to an international study investigating the impact of disconnecting from nature.

Led by the Basque technology center AZTI, and involving the University of Exeter, the study built on pre COVID-19 evidence that access to outdoor spaces benefitted mental health and wellbeing. Researchers sought to answer the question of whether being forced to disconnect from nature affected mental health. The study, published in the journal Science of the Total Environment, was carried out during the first wave of COVID-19 in Europe (March-May 2020).

The team of international researchers from Spain, United Kingdom and Norway invited citizens to voluntarily respond a simple questionnaire to check their behaviour and mental health status in the face of severe measures that restricted mobility. In less than 20 days, 6,769 people from 77 different countries answered the survey, although for analysis purposes we focused on 5,218 responses from 9 countries.

Dr Sarai Pouso, from AZTI, who led the research, said: "The main conclusion is that people who were under the strictest lockdown during the first wave of COVID-19 (those who were only allowed to go out for work or essentials purchases, as was the case of Italy and Spain) were more likely to show symptoms compatible with depression and anxiety, compared to countries with more relaxed lockdowns where people could still visit natural places such as parks."

The researchers analyzed in greater detail the case of Spain, where, due to the epidemiological situation in March, the possibility for practicing outdoor activities, such as walking or playing sports, was totally forbidden. "The results indicate that having access from the home to outdoor spaces (e.g., garden, balcony) and having window views to open spaces or natural element (e.g., coast, park, forest) decreased the probability of showing symptoms of depression. Furthermore, people with access to outdoor spaces and with nature views, managed to maintain a more positive mood during lockdown", adds María C. Uyarra, who together with Dr Ángel Borja and Dr Sarai Pouso, made up the AZTI team involved in the study.

The effects of having access to gardens and views of nature from the home were far less important in countries in where people were allowed, or even encouraged, to visit parks and other natural locations as long as safe social distancing recommendations were adhered to (e.g. Norway, United Kingdom).

Results suggest that, under stressful circumstances such as lockdown, allowing people to spend some time outdoors in nature may help reduce the likelihood of developing symptoms of depression and or anxiety. This may be particularly important for people without gardens or views of nature, who are more likely to have lower incomes and live in more built up urban areas, concluded the research team.

Looking at different population subgroups, women and young people were more likely to experience symptoms of depression and anxiety. However, the researchers remain cautious. "The study was unable to obtain a fully representative sample and did not include data from certain groups that may have been particularly affected by the lockdown situation, such as children or many older adults" says Dr Mat White, from the University of Exeter, United Kingdom.

Results suggest that if governments have to implement new lockdown measures in the near future, they should consider allowing the population to spend some time outdoors. "Spending time outdoors has a protective effect on mental health. Restoring and expanding green and blue spaces in urban areas increases the resilience of cities in the face of pandemics", adds Erik Gómez-Baggethun, Professor at the Norwegian University of Life Sciences.

The study proposes that future urban developments should pay special attention to the inclusion of elements that would enable to contact with nature (e.g., more green areas in public spaces, etc.), as well as special attention to the most vulnerable sectors of the population.

"This research is important for so that future planners take into account that is crucial for people to have equal access to high-quality blue and green environments. We have now contributed to a robust and compelling body of evidence that tells us this access can both prevent and treat mental health issues, especially in urban areas. This is particularly key in the context of a pandemic, but actually it should be a planning priority that could improve our health, regardless of COVID-19" adds Lora E. Fleming, director of the European Centre for Environment and Human Health, from the University of Exeter.

"In summary, this study shows that the strict lockdown isolation to which certain populations (e.g., in Spain) were exposed had a negative effect on their mental health. However, we still do not know if these symptoms have been persistent or if they disappeared once the lockdown measures ended", concludes Dr Pouso.

Researchers have used AI to control beams for the next generation of smaller, cheaper accelerators for research, medical and industrial applications.

Experiments led by Imperial College London researchers, using the Science and Technology Facilities Council's Central Laser Facility (CLF), showed that an algorithm was able to tune the complex parameters involved in controlling the next generation of plasma-based particle accelerators.

The algorithm was able to optimize the accelerator much more quickly than a human operator, and could even outperform experiments on similar laser systems.

These accelerators focus the energy of the world's most powerful lasers down to a spot the size of a skin cell, producing electrons and x-rays with equipment a fraction of the size of conventional accelerators.

The electrons and x-rays can be used for scientific research, such as probing the atomic structure of materials; in industrial applications, such as for producing consumer electronics and vulcanised rubber for car tyres; and could also be used in medical applications, such as cancer treatments and medical imaging.

Several facilities using these new accelerators are in various stages of planning and construction around the world, including the CLF's Extreme Photonics Applications Centre (EPAC) in the UK, and the new discovery could help them work at their best in the future. The results are published today in Nature Communications.

First author Dr Rob Shalloo, who completed the work at Imperial and is now at the accelerator centre DESY, said: "The techniques we have developed will be instrumental in getting the most out of a new generation of advanced plasma accelerator facilities under construction within the UK and worldwide.

"Plasma accelerator technology provides uniquely short bursts of electrons and x-rays, which are already finding uses in many areas of scientific study. With our developments, we hope to broaden accessibility to these compact accelerators, allowing scientists in other disciplines and those wishing to use these machines for applications, to benefit from the technology without being an expert in plasma accelerators."

The team worked with laser wakefield accelerators. These combine the world's most powerful lasers with a source of plasma (ionised gas) to create concentrated beams of electrons and x-rays. Traditional accelerators need hundreds of metres to kilometres to accelerate electrons, but wakefield accelerators can manage the same acceleration within the space of millimetres, drastically reducing the size and cost of the equipment.

However, because wakefield accelerators operate in the extreme conditions created when lasers are combined with plasma, they can be difficult to control and optimise to get the best performance. In wakefield acceleration, an ultrashort laser pulse is driven into plasma, creating a wave that is used to accelerate electrons. Both the laser and plasma have several parameters that can be tweaked to control the interaction, such as the shape and intensity of the laser pulse, or the density and length of the plasma.

While a human operator can tweak these parameters, it is difficult to know how to optimise so many parameters at once. Instead, the team turned to artificial intelligence, creating a machine learning algorithm to optimise the performance of the accelerator.

The algorithm set up to six parameters controlling the laser and plasma, fired the laser, analysed the data, and re-set the parameters, performing this loop many times in succession until the optimal parameter configuration was reached.

Lead researcher Dr Matthew Streeter, who completed the work at Imperial and is now at Queen's University Belfast, said: "Our work resulted in an autonomous plasma accelerator, the first of its kind. As well as allowing us to efficiently optimise the accelerator, it also simplifies their operation and allows us to spend more of our efforts on exploring the fundamental physics behind these extreme machines."

The team demonstrated their technique using the Gemini laser system at the CLF, and have already begun to use it in further experiments to probe the atomic structure of materials in extreme conditions and in studying antimatter and quantum physics.

The data gathered during the optimisation process also provided new insight into the dynamics of the laser-plasma interaction inside the accelerator, potentially informing future designs to further improve accelerator performance.

Conventional wisdom has long recognized the power of home court advantage in basketball.

The specific reasons home teams perform better are less clear: Is it the adrenalin fueled by the roar of the crowd? Referees favoring the home team?

What about disruptions of the internal body clock from quickly crossing time zones and poor sleep for the traveling teams?

The body clock and sleep question especially intrigues Andrew McHill, Ph.D., an occupational health scientist at Oregon Health & Science University who specializes in sleep disturbance and circadian rhythms.

In a study published in the journal Scientific Reports, McHill and his colleague closely examined the travel performance of elite professional basketball players. Their conclusion: Whether you're LeBron James or a rec-league scrub who travels for business, your performance on the road depends to a large degree on the alignment of your internal body clock with the new time zone and the quality of your sleep.

"Travel is hard for everyone," McHill said. "If you're a businessman who needs to present a sales pitch, being accurate and precise could be very important. This study suggests that small misalignments between the internal body clock and a new time zone (i.e., jet lag) can impact your accuracy and impair performance. To best adapt, you'll want to get acclimated to your new time zone as quickly as possible."

The weirdly truncated pro basketball season of 2019-20 afforded a prime opportunity for a natural experiment.

After halting its season in March due to the COVID-19 pandemic, the National Basketball Association resumed the last two months of the season in July with the 22 top teams confined to play in a travel-less "bubble" within Walt Disney World in Orlando, Florida.

"I'm a big sports fan, and I always wanted to look at how travel - and potentially jet lag and sleep disturbance - impacts sports performance," he said. "When the NBA suspended its season, and then started this bubble experiment in Orlando, I realized it was an opportunity to do what I'd been thinking about for a long time."

McHill partnered with a grad school colleague, Evan Chinoy, a sleep and circadian physiologist who works in San Diego for Leidos Inc., a biomedical research firm.

The researchers used this unique opportunity to compare the performance of teams during travel before the COVID-19 pandemic with the performance of those same teams comfortably ensconced at Disney World.

In their analysis, McHill and Chinoy were able to discern statistically significant differences in performance among teams that traveled within their time zone and across time zones. Specifically, researchers found teams that didn't travel had improved shooting accuracy and rebounding, although McHill said the detriments may be attributed to different factors.

"Shooting was affected by travel across time zones, whereas rebounding was impacted by travel in general," McHill said.

When a team travels across the country into different time zones, the mismatch between the new time zone and the team's home time zone has a physiological effect in a very specific part of the body: the suprachiasmatic nucleus of the brain's hypothalamus. In a precise activity like shooting a basketball, even slightly disrupting a player's central circadian clock could be the difference between a ball that swishes through the net and one that rattles in and out of the rim.

The study found that shooting accuracy in the bubble improved significantly.

"Everyone was shooting better," McHill said. "There was a lot more scoring. In any given game, you didn't have one team that was shooting worse like you normally would."

Rebounding, by contrast, is an activity that tends to reflect brute-force effort.

The study found that visiting teams didn't rebound as well, whether the game was played within its own time zone or three time zones away. This is likely due to the fact that a player is apt to get a good night's sleep at home compared to sleeping in a hotel.

Notably, the overall decline in performance appeared to be disproportionately experienced by East Coast teams traveling west.

"Most NBA games start at 7 or 8 p.m., so when the New York Knicks play in Portland, they are really starting the game at 11 p.m. on their body clock," he said. "By the time it's crunch time late in the fourth quarter, it may be 2 a.m. on their clock while it's 11 p.m. for the Blazers."

By contrast, the Blazers typically tip off at 4 p.m. Portland time during their East Coast road trips.

This would seem to be an advantage for Western Conference teams, which have won 15 of the 22 NBA championship series played since Michael Jordan and the Chicago Bulls dynasty of the 1990s. McHill, a longtime Blazers fan with searing childhood memories of the team falling just short of the NBA Finals in 2000, discounts this.

"It gets confounded by the fact that the Western Conference has had so many great players over the years," he said. "I'm also a baseball fan. Think about how the Mariners have struggled over the years, and that argument somewhat goes out the window."

Either way, McHill said his findings suggest that NBA teams may be better off boarding a plane for the next city immediately after their previous game ends - as opposed to staying overnight and then flying the next day.

"To best adapt to a new time zone, you'll want to arrive at your 'away' destination as soon as possible," he said. "This study may suggest it's worth getting acclimated to your new time zone as quickly as possible. It may mean flying after the game, even though it's late.

"This type of schedule would have to be evaluated on a game-by-game basis, as you also don't want to impact sleep too greatly. It's a fine balance that still needs to be worked out."

Researchers at the Francis Crick Institute and University College London have rebuilt a human thymus, an essential organ in the immune system, using human stem cells and a bioengineered scaffold. Their work is an important step towards being able to build artificial thymi which could be used as transplants.

The thymus is an organ in the chest where T lymphocytes, which play a vital role in the immune system, mature. If the thymus does not work properly or does not form during foetal development in the womb, this can lead to diseases such as severe immunodeficiency, where the body cannot fight infectious diseases or cancerous cells, or autoimmunity, where the immune system mistakenly attacks the patient's own healthy tissue.

In their proof-of-concept study, published in Nature Communications today [Friday 11th December], the scientists rebuilt thymi using stem cells taken from patients who had to have the organ removed during surgery. When transplanted into mice, the bioengineered thymi were able to support the development of mature and functional human T lymphocytes.

While researchers have previously rebuilt other organs or sections of organs, this is the first-time scientists have successfully rebuilt a whole working human thymus. The study, which was mainly funded by the European Research Council (ERC),* is an important step not only for further research into and treatment of severe immune deficiencies but also more broadly for developing new techniques to grow artificial organs.

Sara Campinoti, author and researcher in the Epithelial Stem Cell Biology and Regenerative Medicine Laboratory at the Crick says: "Showing it is possible to build a working thymus from human cells is a crucial step towards being able to grow thymi which could one day be used as transplants".

To rebuild this organ, the researchers collected thymi from patients and in the laboratory, grew thymic epithelial cells and thymic interstitial cells from the donated tissue into many colonies of billions of cells.

The next step for the researchers was to obtain a structural scaffold of thymi, which they could repopulate with the thymic cells they had cultured. For this, researcher Asllan Gjinovci developed a new approach to remove all the cells from rat thymi, so only the structural scaffolds remained. They had to use a new microvascular surgical approach for this, as conventional methods are not effective for the thymus.

Asllan says: "This new approach is important because it enables us to obtain scaffolds from larger organs like the human thymus, something essential to bringing this beautiful work to the clinic."

The researchers then injected the organ scaffolds with up to six million human thymic epithelial cells as well as interstitial cells from the colonies they had grown in the lab. The cells grew onto the scaffolds and after only five days, the organs had developed to a similar stage as those seen in nine-week old foetuses.

Finally, the team implanted these thymi into mice. They found that in over 75% of cases, the thymi were able to support the development of human lymphocytes.

Roberta Ragazzini, another author of the paper, adds: "The fact that we can extensively expand thymic stem cells taken from human donors into large colonies is really exciting. It makes it possible to scale up the process with a view to build 'human size' thymi."

Paola Bonfanti, senior author and group leader at the Crick and professor in the Division of Infection and Immunity at UCL says: "As well as providing a new source of transplants for people without a working thymus, our work has other potential future applications.

"For example, as the thymus helps the immune system to recognise self from non-self, it poses a problem for organ transplants as it can cause the immune system to attack the transplant.

"It is possible that we could overcome this by also transplanting a thymus regrown from cells taken from the thymus of the organ donor. We are confident that this may prevent the body attacking the transplant. The research behind this is still in early days, but it is an exciting concept which could remove the need for patients to take immune suppressors for the rest of their life.

The researchers are continuing their work rebuilding thymi to refine and scale up the process.

TAMPA, Fla (Dec. 11, 2020) -- The appealing array of fruit and candy flavors that entice millions of young people take up vaping can harm their hearts, a preclinical study by University of South Florida Health (USF Health) researchers found.

Mounting studies indicate that the nicotine and other chemicals delivered by vaping, while generally less toxic than conventional cigarettes, can damage the lungs and heart. "But so far there has been no clear understanding about what happens when the vaporized flavoring molecules in flavored vaping products, after being inhaled, enter the bloodstream and reach the heart," said the study's principal investigator Sami Noujaim, PhD, an associate professor of molecular pharmacology and physiology at the USF Health Morsani College of Medicine.

In their study published Nov. 20 in the American Journal of Physiology- Heart and Circulatory Physiology, Dr. Noujaim and colleagues report on a series of experiments assessing the toxicity of vape flavorings in cardiac cells and in young mice.

"The flavored electronic nicotine delivery systems widely popular among teens and young adults are not harm-free," Dr. Noujaim said. "Altogether, our findings in the cells and mice indicate that vaping does interfere with the normal functioning of the heart and can potentially lead to cardiac rhythm disturbances."

Dr. Noujaim's laboratory is among the first beginning to investigate the potential cardiotoxic effects of the many flavoring chemicals added to the e-liquids in electronic nicotine delivery systems, or ENDS. He recently received a five-year, $2.2-million grant from the NIH's National Institute of Environmental Health Sciences to carry out this laboratory research. Commonly called e-cigarettes, ENDS include different products such as vape pens, mods, and pods.

Vaping involves inhaling an aerosol created by heating an e-liquid containing nicotine, solvents such as propylene glycol and vegetable glycerin, and flavorings. The vaping device's battery-powered heat converts this e-liquid into a smoke-like aerosolized mixture (e-vapor). Manufacturers tout e-cigarettes as a tool to help quit smoking, but evidence of their effectiveness for smoking cessation is limited, and they are not FDA approved for this use. E-cigarettes contain the same highly addictive nicotine found in tobacco products, yet many teens and young adults assume they are safe.

Among the USF Health study key findings:

- In mouse cardiac muscle cells (HL-1 cells), the researchers tested the toxicity of three different, popular flavors of e-liquid: fruit flavor, cinnamon, and vanilla custard. All three were toxic to HL-1 cells exposed to e-vapor bubbled into the laboratory dish where the cells were cultured.

- Cardiac cells derived from human pluripotent stem cells were exposed to three distinct e-vapors. The first e-vapor containing only solvent interfered with the electrical activity and beating rate of cardiac cells in the dish. A second e-vapor with nicotine added to the solvent increased the toxic effects on these cells. The third e-vapor comprised of nicotine, solvent, and vanilla custard flavoring (the flavor previously identified as most toxic) augmented damage to the spontaneously beating cells even more. "This experiment told us that the flavoring chemicals added to vaping devices can increase harm beyond what the nicotine alone can do," Dr. Noujaim said.

- Healthy young mice implanted with tiny electrocardiogram devices were exposed to 60 puffs of vanilla-flavored e-vapor five days a week, for 10 weeks. Heart rate variability (HRV) - that is, fluctuations in the time interval between successive heartbeats - decreased in these test mice compared to the control mice that inhaled only puffs of air under the same regimen. A sophisticated analysis by the USF Health researchers showed that vaping interfered with normal HRV in the mice by disrupting the autonomic nervous system's control of heart rate (the acceleration and slowing down of heartbeats), Dr. Noujaim said.

- Finally, mice exposed to vaping were more prone to an abnormal and dangerous heart rhythm disturbance known as ventricular tachycardia compared to control mice.

Whether the mouse findings will translate to people is unknown. Dr. Noujaim emphasizes that more preclinical and human studies are needed to further determine the safety profile of flavored ENDS and their long-term health effects.

A partial government ban on flavored e-cigarettes aimed at stopping young people from vaping focused on enforcement against flavored e-cigarettes with pre-filled cartridges, like those produced by industry leader JUUL. However, teens quickly switched to newer disposable e-cigarettes still sold in a staggering assortment of youth-appealing fruity and dessert-like flavors.

"Our research matters because regulation of the vaping industry is a work in progress," Dr. Noujaim said. "The FDA needs input from the scientific community about all the possible risks of vaping in order to effectively regulate electronic nicotine delivery systems and protect the public's health. At USF Health, in particular, we will continue to examine how vaping may adversely affect cardiac health."

The strong foundation of global health research and development (R&D) that greatly accelerated the development of COVID-19 innovations is now being weakened by pandemic pressures that are diverting funding and expertise away from other dangerous diseases and putting clinical trials and scientific endeavors around the world on indefinite hold.

That's a key conclusion of a new report released today from the non-profit Global Health Technologies Coalition (GHTC). It's based on qualitative interviews with experts in academia, philanthropy, industry, government agencies and product development partnerships discussing how the battle against one all-consuming global health threat--COVID-19--is affecting efforts to combat a wide range of other diseases still sickening and killing millions of people worldwide.

"A lot of veterans of global health R&D are confronting a confounding situation of a pandemic that has generated new appreciation for the value of their work while at the same time potentially causing long-term harm to the field," said GHTC Director Jamie Bay Nishi. "Global health R&D has always subsisted on thin budgets and a tight-knit coalition of infectious disease experts--and both of these, funding and talent, are being redirected to COVID-19, which is putting many important projects in a precarious position."

The interviews, conducted anonymously, included experts working at the forefront of developing new innovations for fighting challenging problems like HIV/AIDS, tuberculosis, malaria, dengue and a host of neglected tropical diseases. They discussed how research and product development efforts for poverty-related and neglected diseases, already fighting for resources before COVID-19 hit, are now "at significant risk of disruption due to the pandemic, despite the sector's central role in enabling the COVID-19 R&D response."

One immediate impact is that global health expertise has been in high demand, forcing many researchers to put all other projects aside. The report notes that two people at key U.S. government agencies said that "half their teams have been deployed to COVID-19 response." A representative of a private sector company noted staffing shortages as personnel were diverted to developing COVID-19-related products. There were reports of labs affiliated with academic research institutions, normally focused on various neglected diseases, shifting their staff and facilities to deal with state or university COVID-19 testing demands. In one case, a lab's entire discretionary budget was spent responding to state testing demands, so far without compensation.

Clinical trials--the most costly and complex aspect of developing new health interventions--have been hit especially hard. Nearly every interviewee involved in clinical trials, many of which are located in low- and middle-income countries, reported significant issues, including many being delayed indefinitely. The biggest problems involved the most consequential trials: phase 3 trials that, if successful, are the last hurdle in the long march to product licensure. But they are also the largest and most logistically challenging as they typically involve thousands of participants.

Researchers reported pausing many or all of their late-stage trials. One clinical trial administrator reported that where a trial was already underway, numerous trial participants were not showing up for essential follow-up visits at the clinic because of fear of contracting COVID-19. People managing clinical trials said switching to virtual visits was proving challenging, in part due to infrastructure barriers in low-resource settings--such as the need for many people to regularly purchase new SIM cards for their phones, which changes their phone number--and because many trials require in-person follow-up to collect samples.

It was difficult to assess the impact to global health work at U.S. government agencies like the National Institutes of Health (NIH), the Centers for Disease Control and Prevention (CDC), and the US Agency for International Development (USAID). But the interviews provided reason for concern.

For example, an official at one research center asked staff to estimate the funding they would need to accomplish COVID-19-related work while maintaining existing projects. The estimates were four times higher than the amount of supplemental funding provided by Congress to the center that was supposed to cover those costs. Another agency leader reported trying to hire contract workers to cover COVID-19 work so that existing staff could return to their research projects but acknowledged it can be difficult to backfill positions that require niche expertise.

Meanwhile, many respondents said their work has been stymied by the lack of reagents and personal protective equipment or PPE because both are urgently needed for pandemic-related duties. Even seemingly routine matters like shipping costs to send supplies to global research sites have become big concerns. One researcher working in a high-income country reported that the cost of international shipping had increased six-fold during the pandemic, which would have sapped the entire shipping budget for their five-year NIH grant.

But there were also signs of hope that the pandemic could offer many benefits for the long-term effort to generate new innovations for fighting infectious diseases in low-income countries. One senior government scientist noted that the speed of COVID-19 vaccine development demonstrates to potential funders that, with adequate resources, there could be rapid progress is solving a wide array of global health challenges.

Other interviewees noted that the surge of COVID-19 alliances between governments and industry "has affirmed the value of public-private partnerships for producing new medical products." And there was excitement that new insights and technologies generated over the last few months, along with new approaches to conducting clinical trials, could have applications for many other diseases. The most optimistic opinion, while not universal, involved hopes that the pandemic could create "a new era in which global public health becomes an enduring political priority."

Ultimately, the report predicts global health research will emerge somewhere in the middle. It described the pandemic's impact on global health as operating like a "driverless bulldozer," alternately damaging certain areas while carving promising new paths in others.

"The critical role falls to policy makers to identify and restore vital global health initiatives that have been harmed by the pandemic while capitalizing on opportunities revealed by COVID-19 R&D to accelerate work on a number of diseases," Nishi said. "Their decisions will determine whether the legacy of COVID-19 is a tragic setback for the broader fight against infectious diseases or a new awareness of the incredible value of investing in global health innovations."