Culture

Tsukuba, Japan - With a prevalence of about one in 10 people worldwide, chronic kidney disease (CKD) is a global health problem. It also often goes undetected, leading to a range of negative health outcomes, including death. Catching it at an early stage and adjusting nutrition and lifestyle can improve and extend life, but only if there are economically feasible systems in place to promote and educate on this.

Amid finite health-care resources, any CKD intervention must be both practical and cost-effective. A team of researchers centered at the University of Tsukuba now believe they have found a CKD behavioral intervention that can be delivered at a reasonable cost. They published their findings in the Journal of Renal Nutrition.

Changing eating and lifestyle habits, and regularly visiting a doctor, are vital in managing CKD. Yet the CKD treatment guidelines under Japan's nationalized health-care system offer little economic incentive for general physicians (GPs) to recommend dietitians' valuable guidance for CKD patients.

"There's substantial evidence, including the Japanese Society of Nephrology's clinical guidelines, that dietitian-led patient education can slow the progression of CKD," study corresponding author Professor Masahide Kondo says. "But this sort of education seldom happens in Japan. We sought a way to justify such interventions and incentivize GPs to initiate them."

With a lack of economic assessments of these interventions, the researchers conducted a cost-effectiveness analysis using a Markov model, a mathematical method for finding patterns and making predictions. Based on results from the Frontier of Renal Outcome Modifications in Japan (FROM-J) study, which found success in dietitian-led education and lifestyle advice, along with periodic check-ups, they projected how such intervention would perform economically.

Naturally, a host of factors, such as disease progression and drug costs, play into this complex modeling. Key here was whether the incremental cost-effectiveness ratio (ICER), which shows the unit cost of gaining 1 extra healthy life year among the patients via the intervention, gave sufficient worth for that amount. The estimated ICER of about US$1,324 per quality-adjusted life year (QALY) was compared with the suggested social willingness to pay about US$45,455 for a 1-QALY gain. This demonstrates considerable cost-effectiveness.

"Diffusing such CKD interventions now seems justifiable, even with limited health-care resources," study first author Assistant Professor Reiko Okubo says. "We found that by adjusting the reimbursements and accessing the country's 5,000 registered dietitians, we could incentivize GPs to encourage practical behavioral interventions."

Behavior modification for CKD patients has the potential to be cost-effective within Japan's national health-care scheme. It can also improve and extend lives. Such findings could extend to other countries and encourage them to modify their guidelines. If policy can follow suit and GPs can comply with the advice, CKD can become a more manageable, and less fatal, disease.

A statistically rigorous survey of Japanese consumers has found that they have more negative opinions about the use of new gene-editing techniques on livestock than they do about use of the same technologies on vegetables.

The survey findings were reported in the journal BMC CABI Agriculture and Bioscience on March 31st, 2021.

Because humans tend to feel closer to animals than plants, and commonly express feelings regarding animal welfare but not plant welfare, the researchers, led by Naoko Kato-Nitta, a research scientist at Tokyo's Joint Support Center for Data Science Research and Institute of Statistical Mathematics, wanted to see if such moral or taxonomic distinctions would produce any difference in their attitudes towards use of emerging gene-editing techniques such as CRISPR-Cas9.

Earlier surveys had shown subtle differences in consumer attitudes towards genetic modification, where foreign DNA is inserted into an organism's genome, compared to gene-editing, where an organism's genes are tweaked but no foreign DNA is introduced.

Via an online survey of just over 4,000 participants aged 20 to 69, the researchers found that there was indeed a significant difference. The participants were shown a visual diagram explaining how gene-editing works and then asked how they felt about it. The survey results showed that they were more likely to be worried about the use of gene-editing techniques on livestock than on plants.

But in a twist to the study design, the researchers split the participants into two groups. In the first, the explainer diagram included cartoon pictures of pigs, and in the second, the diagram included cartoon pictures of tomatoes.

The group that had been shown pictures of cartoon pigs were subsequently less likely to raise concerns about gene-editing of livestock than the group that had been shown pictures of cartoon tomatoes. The researchers believe that this may be because the pictures of the pigs "primed" the survey participants to be open to livestock gene-editing. "In contrast, the group shown the gene-editing of cartoon tomatoes had in effect been asked to infer how they would feel if the same thing was done on pigs" says Naoko Kato-Nitta, the lead author of the paper and a specialist in risk communication at ROIS and the Institute of Statistical Mathematics in Tokyo. "There was a higher emotional hurdle to be overcome in the second group."?"This means that public attitudes towards food can change as a result of just one small change to how information is provided," she adds. "And so experts really need to pay careful attention to the impact of how they contextualize their discussions of gene-editing."

The survey participants were also asked a series of questions assessing their level of scientific literacy. The researchers found that those with higher levels of scientific literacy were more supportive of using gene-editing to deliver improvements in vegetables, and more supportive of using gene-editing to make livestock more resistant to disease. Those with higher levels of scientific literacy thus may be more open to medical applications of biotechnology than agri-food applications.

In the 1990s, strong public opposition to genetically modified crops led to the Japanese government's introduction of strict regulations on such techniques, as well as the labeling of GM food items. Currently there is no commercial cultivation of GM crops in the country. And so the researchers now want to perform the study again in other countries in order to see if the plant-animal consumer distinction is culturally specific to Japan.

Scientists from the Genomic Integrity and Structural Biology Group led by Rafael Fernández-Leiro at the Spanish National Cancer Research Centre (CNIO) have discovered how certain proteins ensure the repair of errors introduced into the DNA during its replication. Using cryo-electron microscopy, they made the MutS protein, also known as the guardian of our genome, visible. That enabled them to describe how this single protein is able to coordinate the essential DNA repair process from beginning to end.

The study was carried out in collaboration with Meindert Lamers of the Leiden University Medical Center (LUMC, The Netherlands) and Titia Sixma of the Netherlands Cancer Institute and the Oncode Institute. Their results are published in Nature Structural & Molecular Biology.

One of the stages of cell division is DNA replication, during which DNA polymerase duplicates the genetic information of the cell so that it can be transferred to the daughter cell. Although this is a very precise process, errors do sometimes occur. It is essential that these errors are repaired, as they can otherwise lead to the development of tumours.

The researchers had already described in previous publications that DNA polymerase has its own repairer, an exonuclease, which allows it to correct errors that are introduced during DNA replication. But when this corrector is not sufficient, the MutS protein comes into play, which scans the copied DNA for errors and then initiates and completes the repair of any errors it detects. But until now, it was not clear how a single protein could coordinate so many different processes. The international study now published has succeeded in unravelling the mechanism.

"Using cryo-electron microscopy, we were able to observe MutS while it carried out its functions and capture its molecular structure in successive conformations. With this information, we were able to understand how a single protein can coordinate the whole process, which has to be extremely accurate," explains Rafael Fernández-Leiro.

In-depth knowledge of the DNA repair process, in which DNA polymerase, exonuclease and the MutS protein are involved, is essential to understand how alterations in any of these proteins lead to mutations and, therefore, to an increased risk of developing certain types of tumour, such as Lynch syndrome and endometrial cancer.

The researchers emphasise that unravelling protein structures is only possible due to the enormous technological advances in electron microscopy in recent years.

"Electron microscopy allows us to obtain very high-resolution images of proteins as they carry out their functions. With these images, we can reconstruct the three-dimensional structure of the protein in the computer and generate an atomic model that allows us to understand how it works," continues Fernández-Leiro.

A new study analyzing bean production and food security across 11 countries in sub-Saharan Africa, found COVID-19 pandemic-related restrictions to significantly impact bean production. Border controls and high transport costs have led to drops in production of the key food security crop, threatening to reverse gains made in achieving Sustainable Development Goals 1 and 2, towards no poverty and zero hunger, respectively.

Even before the pandemic, 55% of the world's hungry people and 70% of the world's poorest people lived in Africa, the researchers said. In addition, food systems across Africa were already affected by the adverse impacts of climate change, disease and pests, such as the worst desert locust outbreak in 70 years impacting food security in Kenya, Somalia, Ethiopia and other countries in eastern Africa.

Other impacts of COVID-19 restrictions, both direct and indirect, can be found in the study: "Regional impact of COVID-19 on the production and food security of common bean smallholder farmers in Sub-Saharan Africa: Implication for SDG's," published in the Global Food Security edition of peer-reviewed platform Science Direct. Direct impacts include farms and food businesses closing down; while indirect impacts are linked to lockdown, border closures, social distancing, and restricted transportation and trade.

"The food system is already highly inefficient. What we've seen is that measures taken to control the virus led to wider food security restrictions and disruptions, exacerbating those already-existing insecurities," said author Eileen Nchanji, a gender researcher at The Alliance of Bioversity International and the International Center for Tropical Agriculture (The Alliance). "Pay cuts, job losses, and high food prices due to reduced food imports and closure of informal markets all disrupted food supplies, with poorer communities especially affected."

From border closures to national lockdowns, delayed cargo further exacerbated food shortages, the researchers said. For instance, 15% of imported food in Kenya before the pandemic was sourced from countries that imposed export restrictions, affecting the availability and flow of crops and food. Restrictions also led to limited access to seed, farm inputs, hired labor, and agricultural finance for smallholder farmers, especially those in Uganda, where planting was beginning.

The data, collected between March and April 2020, shows that most households in Eastern Africa ate only twice during the pandemic. Uganda was most affected, with all surveyed farmers eating only once per day during the pandemic. The research also found a 34% decrease in access to labor attributed to the fear of getting the disease, the high cost of public transportation, and social distancing measures. Farmers also noted difficulties in accessing finance, farm inputs, seed and extension information.

The research highlights that 36%, 20%, and 3% of farmers in Burundi, Uganda, and Kenya respectively lost income during the pandemic, with knock-on impacts on food security. The low number in Kenya is due to the fact that crops were already planted, and farmers were relying on maize and other crops stored from the previous harvest for food and to generate income, while in Uganda and Burundi, planting was ongoing, and so more money was spent on inputs, seed and food, as prices and costs of transport increased.

In West Africa, challenges included insecurity, political instability, social conflicts, and climate change, the report said, citing Food and Agriculture projections that 17 million people in the region will face severe food insecurity following measures to contain the virus.

Although governments across the continent have responded by offering economic stimulus packages, much needs to be done to enable the sub-sector to recover from ruins caused by the pandemic, authors said.

Cosmas Lutomia, at the Kenya Agriculture and Livestock Research Organization (KALRO), said: "The pandemic has necessitated a much needed discussion around the complexity of our food systems. We can only achieve sustainable and resilient food systems through strengthening public-private partnerships. We implore governments across the region to strengthen the food systems' resilience to present and future shocks."

The authors called for an immediate transformation of food systems in all the sub-regions. Governments should invest directly in input supply systems and short food supply chains through digital access, mobile-based payments, credit and food delivery, they added.

3-D printing has the potential to revolutionize product design and manufacturing in a vast range of fields--from custom components for consumer products, to 3-D printed dental products and bone and medical implants that could save lives. However, the process also creates a large amount of expensive and unsustainable waste and takes a long time, making it difficult for 3-D printing to be implemented on a wide scale.

Each time a 3-D printer produces custom objects, especially unusually-shaped products, it also needs to print supports­-printed stands that balance the object as the printer creates layer by layer, helping maintain its shape integrity. However, these supports must be manually removed after printing, which requires finishing by hand and can result in shape inaccuracies or surface roughness. The materials the supports are made from often cannot be re-used, and so they're discarded, contributing to the growing problem of 3-D printed waste material.

For the first time, researchers in USC Viterbi's Daniel J. Epstein Department of Industrial and Systems Engineering have created a low-cost reusable support method to reduce the need for 3-D printers to print these wasteful supports, vastly improving cost-effectiveness and sustainability for 3-D printing.

The work, led by Yong Chen, professor of industrial and systems engineering and PhD student Yang Xu, has been published in Additive Manufacturing.

Traditional 3-D printing using the Fused Deposition Modeling (FDM) technique, prints layer-by-layer, directly onto a static metal surface. The new prototype instead uses a programmable, dynamically-controlled surface made of moveable metal pins to replace the printed supports. The pins rise up as the printer progressively builds the product. Chen said that testing of the new prototype has shown it saves around 35% in materials used to print objects.

"I work with biomedical doctors who 3-D print using biomaterials to build tissue or organs," Chen said. "A lot of the material they use are very expensive­-we're talking small bottles that cost between $500 to $1000 each."

"For standard FDM printers, the materials cost is something like $50 per kilogram, but for bioprinting, it's more like $50 per gram. So if we can save 30% on material that would have gone into printing these supports, that is a huge cost saving for 3-D printing for biomedical purposes," Chen said.

In addition to the environmental and cost impacts of material wastage, traditional 3-D printing processes using supports is also time-consuming, Chen said.

"When you're 3-D printing complex shapes, half of the time you are building the parts that you need, the other half of the time you're building the supports. So with this system, we're not building the supports. Therefore, in terms of printing time, we have a savings of about 40%."

Chen said that similar prototypes developed in the past relied on individual motors to raise each of the mechanical supports, resulting in highly energy-intensive products that were also much more expensive to purchase, and thus not cost-effective for 3-D printers.

"So if you had 100 moving pins and the cost of every motor is around $10, the whole thing is $1,000, in addition to 25 control boards to control 100 different motors. The whole thing would cost well over $10,000."

The research team's new prototype works by running each of its individual supports from a single motor that moves a platform. The platform raises groups of metal pins at the same time, making it a cost-effective solution. Based on the product design, the program's software would tell the user where they need to add a series of metal tubes into the base of the platform. The position of these tubes would then determine which pins would raise to defined heights to best support the 3-D printed product, while also creating the least amount of wastage from printed supports. At the end of the process, the pins can be easily removed without damaging the product.

Chen said the system could also be easily adapted for large scale manufacturing, such as in the automotive, aerospace and yacht industries.

"People are already building FDM printers for large size car and ship bodies, as well as for consumer products such as furniture. As you can imagine, their building times are really long--we're talking about a whole day," Chen said. "So if you can save half of that, your manufacturing time could be reduced to half a day. Using our approach could bring a lot of benefits for this type of 3-D printing."

Chen said the team had also recently applied for a patent for the new technology. The research was co-authored by Ziqi Wang, previously a visiting student at USC, from the School of Computer and Communication Sciences, EPFL Switzerland, and Siyu Gong from USC Viterbi.

Likely the first extinction event of the 2000s in Europe, the sad history of the Pyrenean Ibex (Capra pyrenaica pyrenaica) is a powerful example of the ever-increasing species loss worldwide due to causes related to human activity. It can, however, give us valuable information on what should be done (or avoided) to halt this extinction vortex.

The distribution of this subspecies of Iberian Ibex was limited to the French and Spanish Pyrenees. Its first mention in an official written document, dating back to 1767, already refers to it as extremely rare. Like many other mountain goats, it was almost hunted to extinction before its killing became prohibited in 1913. Neither the institution of a national park (Ordesa & Monte Perdido), nor a conservation project with European LIFE program funding could stop the extinction of the Pyrenean Ibex eventually officialised on January 6, 2000. But the story of this charismatic animal did not end there - a controversial cloning program was started instantly with no scientific agreement, nor support from regional environmental NGOs, claiming that de-extinction was possible even in the absence of further DNA studies.

To find out more about the drivers of its extinction, an international team composed of 7 nationalities built a database of all known museum specimens and reconstructed the demographic history of the Pyrenean Ibex based on DNA evidence. Their research is published in the open-access, peer-reviewed journal Zoosystematics and Evolution.

The research found that after a population expansion between 14,000 and 29,000 years ago (which is quite recent from a genetic point of view), a significant loss of genetic diversity followed between approximately 15,000 and 7,500 years BP, and continued until present. By that time, the Pyrenean Ibex also lived outside the Pyrenean mountain chain, but, gradually, its distribution was reduced to only one valley in the Ordesa National Park in the Spanish Pyrenees.

Written sources confirm hunting of the Pyrenean Ibex from as early as the 14th century, and during the 19th and 20th century it became a common target for trophy hunters. Undoubtedly, hunting played an important role in reducing its population numbers and distribution area, but it is not possible - with the information currently available - to pinpoint it as the straw that broke the camel's back. Infectious diseases that originate from livestock (for instance, those caused by the bluetongue virus, BTV, and sarcopses) are capable of decimating other subspecies of Iberian Ibex in extremely short periods of time.

While the relative contribution of various factors remains largely unknown, it seems that hunting and diseases transmitted from other animals have been effective in drastically reducing the number of Pyrenean ibexes over the last two centuries, because they were acting on an already genetically weakened population. This low genetic diversity, combined with inbreeding depression and reduced fertility, brought the population beyond the minimum viable size - from that point onwards, extinction was inevitable.

This case study shows the importance of historical biological collections for genetic analyses of extinct species. A privately owned 140-year-old trophy preserved in Pau, France, was genotyped as part of this research, showing that private individuals may possess material of high value. As there is little knowledge of such resources, the authors call for the creation of an online public database of private collections hosting biological material for the benefit of biodiversity studies.

Insomnia is a common problem in patients with schizophrenia, and a new study reinforces a close association between insomnia, more suicidal thoughts and actions and increased problems like anxiety and depression in these patients.

It also provides more evidence that keeping tabs on how patients are sleeping -- and intervening when needed -- is important to their overall care.

"We are now aware that significant insomnia is putting our patients at even higher risk for suicide, so if they are having changes in sleep patterns, if they are having significant insomnia, then we really need to hone in on those questions even more related to suicidal thinking and do what we can to help," says Dr. Brian Miller, psychiatrist and schizophrenia expert at the Medical College of Georgia at Augusta University.

Schizophrenia is clearly associated with an increased risk of suicide, with a 5-10% lifetime risk of death by suicide, that is likely the greatest within the first year of diagnosis, Miller says.

The new study in The Journal of Clinical Psychiatry looked at associations between insomnia, suicidal thoughts and attempts and disease severity in a large group of patients, 1,494 individuals diagnosed at 57 sites in the country, and enrolled in a comparative study of five different antipsychotics.

Miller and his colleagues looked at patient reports of insomnia and suicidal thoughts within the most recent two weeks, suicide attempts in the past six months and the state of their psychiatric illness when they enrolled in the study.

Nearly half of patients reported problems falling asleep or broken sleep, termed initial and middle insomnia, and 27% reported terminal insomnia where they wake up too early and cannot get back asleep.

They found insomnia a common symptom in patients with schizophrenia, with waking up too early particularly associated with current suicidal thoughts, and trouble falling and staying asleep significantly increasing the odds of a suicide attempt in the past six months.

Waking up too early was also most associated with more severe schizophrenia, including symptoms like anxiety and depression. But no matter which type of insomnia, it's bad for patients' overall health and disease, Miller says.

Studies indicate that 23-44% of patients with schizophrenia -- both those taking and not taking medications-- report problems with insomnia. Sleep architecture is a pattern of normal sleep, and sleep disturbances and abnormal sleep architecture have been found early in the schizophrenia disease process, findings which may correlate with disease severity. Disturbances in the natural body clocks, or circadian rhythms that help regulate sleep and wakefulness and other essential body functions, are known to be present in schizophrenia and are suspected to be a factor in patients' related sleep problems. A generally heightened state of arousal in patients who are hearing voices and/or paranoid also is likely a factor. Insomnia has been implicated as a predictor of hallucinations in patients, and there seems to be a bidirectional relationship between insomnia and paranoia, the investigators write.

"If you are hearing voices that are constantly saying negative, horrible things, berating you, interfering with your thinking and your activities, it can be hard to fall asleep," he says.

Miller says insomnia in his patients cuts across all ages, sexes and races.

While he has always been diligent asking patients at each visit about their sleep and counseling them on how to improve their sleep, the increasing evidence of the association with suicide and disease severity has heightened his diligence. While Miller says his colleagues across the country also tend to be diligent in regularly talking with patients about sleep, surveys have indicated that while patients with schizophrenia commonly report problems with insomnia, less than 20% of clinicians formally evaluate patients for it.

The new study suggests that insomnia is an important treatment target in schizophrenia. Interventions Miller offers include ensuring habits like avoiding caffeine as well as blue light from commons sources like televisions and smartphones, particularly in the hours before bedtime, as well as prescription and over-the-counter sleep aids.

Adjustments also can be made to the antipsychotic medication used to treat their schizophrenia since some, like clozapine, also have sedative effects. In fact, there is some evidence that insomnia and suicidal thoughts and actions are less likely in patients taking antipsychotics known to also have a sedative effect, they write, but just how needs exploration.

While he has not yet done a formal study, Miller has noted anecdotally that when his patients' sleep improves, generally their schizophrenia does as well.

"I can't think of anyone who says I am sleeping better and now my illness is worse. When you get a bad night's sleep, the world just isn't quite the same place the next day," Miller says. "It affects the way we think about things, the judgements we make, it affects our emotions." In fact, insomnia and increased suicide risk are associated with a variety of mental health issues, including depression.

The current study is the third group of patients in which Miller and his colleagues have found an association between insomnia and suicidal thoughts and actions.

Other investigators have associated sleep disturbances with suicidal thoughts in these patients but not actual suicide; others have shown, for example, nearly five times the risk of suicide attempts in patients experiencing insomnia at least three times a week.

Study using electronic health records of 236,379 COVID-19 patients mostly from the USA estimates that one in three COVID-19 survivors (34%) were diagnosed with a neurological or psychiatric condition within six months of infection.

Anxiety (17%) and mood disorders (14%) were the most common. Neurological diagnoses such as stroke and dementia were rarer, but not uncommon in those who had been seriously ill during COVID-19 infection. For example, of those who had been admitted to intensive care, 7% had a stroke and almost 2% were diagnosed with dementia.

These diagnoses were more common in COVID-19 patients than in flu or respiratory tract infection patients over the same time period, suggesting a specific impact of COVID-19.

Authors say their findings should aid service planning and highlight need for ongoing research.

One in three COVID-19 survivors received a neurological or psychiatric diagnosis within six months of infection with the SARS-CoV-2 virus, an observational study of more than 230,000 patient health records published in The Lancet Psychiatry journal estimates. The study looked at 14 neurological and mental health disorders [1].

Professor Paul Harrison, lead author of the study, from the University of Oxford, UK, said: "These are real-world data from a large number of patients. They confirm the high rates of psychiatric diagnoses after COVID-19, and show that serious disorders affecting the nervous system (such as stroke and dementia) occur too. While the latter are much rarer, they are significant, especially in those who had severe COVID-19." [2]

"Although the individual risks for most disorders are small, the effect across the whole population may be substantial for health and social care systems due to the scale of the pandemic and that many of these conditions are chronic. As a result, health care systems need to be resourced to deal with the anticipated need, both within primary and secondary care services." [2]

Since the COVID-19 pandemic began, there has been growing concern that survivors might be at increased risk of neurological disorders. A previous observational study by the same research group reported that COVID-19 survivors are at increased risk of mood and anxiety disorders in the first three months after infection [3]. However, until now, there have been no large-scale data examining the risks of neurological as well as psychiatric diagnoses in the six months after COVID-19 infection.

This latest study analysed data from the electronic health records of 236,379 COVID-19 patients from the US-based TriNetX network, which includes more than 81 million people. Patients who were older than 10 years and who became infected with the SARS-CoV-2 virus after 20 January 2020, and were still alive on 13 December 2020, were included in the analysis. This group was compared with 105,579 patients diagnosed with influenza and 236,038 patients diagnosed with any respiratory tract infection (including influenza).

Overall, the estimated incidence of being diagnosed with a neurological or mental health disorder following COVID-19 infection was 34%. For 13% of these people it was their first recorded neurological or psychiatric diagnosis.

The most common diagnoses after COVID-19 were anxiety disorders (occurring in 17% of patients), mood disorders (14%), substance misuse disorders (7%), and insomnia (5%). The incidence of neurological outcomes was lower, including 0.6% for brain haemorrhage, 2.1% for ischaemic stroke, and 0.7% for dementia (see table 2).

Risks of a neurological or psychiatric diagnosis were greatest in, but not limited to, patients who had severe COVID-19. Compared to the overall 34% incidence, a neurological or psychiatric diagnosis occurred in 38% of those who had been admitted to hospital, 46% of those in intensive care, and 62% in those who had delirium (encephalopathy) during their COVID-19 infection. This gradient of risk applied to individual disorders too. For example, 2.7% of people needing intensive care and 3.6% of people with encephalopathy had a brain haemorrhage (compared to 0.3% in people without hospitalisation); 6.9% and 9.4% had ischaemic stroke (compared to 1.3% without hospitalisation); 1.7% and 4.7% developed dementia (0.4% without hospitalisation); and 2.8% and 7% were diagnosed with a psychotic disorder (0.9% without hospitalisation) (see table 2).

The authors also looked at people who experienced flu and other respiratory tract infections over the same time frame to help understand whether these neurological and mental health complications were linked specifically to COVID-19. After taking into account underlying health characteristics, such as age, sex, ethnicity, and existing health conditions, there was overall a 44% greater risk of neurological and mental health diagnoses after COVID-19 than after flu, and a 16% greater risk after COVID-19 than with respiratory tract infections. As a result, the authors say that COVID-19 does lead to a greater risk of neurological and psychiatric disorders than these other health conditions. However, this was not seen for all conditions; there was no clear evidence that COVID-19 led to an increased risk of parkinsonism or and Guillain-Barré syndrome.

Dr Max Taquet, a co-author of the study, from the University of Oxford, UK, said: "Our results indicate that brain diseases and psychiatric disorders are more common after COVID-19 than after flu or other respiratory infections, even when patients are matched for other risk factors. We now need to see what happens beyond six months. The study cannot reveal the mechanisms involved, but does point to the need for urgent research to identify these, with a view to preventing or treating them." [2]

The authors note several limitations to their study. Firstly, the completeness and accuracy of the electronic health records is not known. Secondly, many people with COVID-19 have mild or no symptoms and do not present for health care, therefore, the people studied here are likely to have been more severely affected than in the general population. Thirdly, the severity and course of the neurological and psychiatric disorders is not known.

Writing in a linked Comment article, Dr Jonathan Rogers, who was not involved in the study, from University College London (UCL), UK, said: "[this] study points us towards the future, both in its methods and implications. Researchers need to be able to observe and anticipate the neurological and psychiatric outcomes of future emerging health threats by use of massive, international, real-world clinical data. Selection biases will remain an issue, not necessarily mitigated by sample size,10 and thus the onus should be on countries with public health-care systems to enable truly comprehensive national data to be available for research. Sadly, many of the disorders identified in this study tend to be chronic or recurrent, so we can anticipate that the impact of COVID-19 could be with us for many years."

CORVALLIS, Ore. - At a time when lumber prices are skyrocketing, an Oregon State University researcher has developed a new way to predict the future price of logs that uses readily accessible economic information.

"Log prices are really variable," said Jeff Reimer, a professor of applied economics at Oregon State. "That makes this a difficult business, whether you are land manager, mill owner, timberland investor or, as we are seeing now, a home builder."

The timber industry is critical to the economy of many regions of the world, including the Pacific Northwest. The health of the timber industry can be measured in various ways, including harvest levels, employment in timber harvesting and at mills, and lumber demand. Yet the prices of cut and delivered logs may be the most direct way to monitor the condition of timber markets, Reimer said.

Reimer's study, recently published in the journal Forest Policy and Economics, focused on Douglas-fir, the most commercially important timber species in the Pacific Northwest.

He found that simply knowing the number of housing permits issued in a month can explain about 46.8% of the variation in log prices over time. Adding additional information - including the monthly inventory of homes, mortgage rates, the exchange rate with Canada (also a big timber supplier) and the Case-Shiller home price index - explains about 74.3% of the price variation.

"These variables are readily observable and thus can be used by industry decision-makers to make better predictions about future values of logs and timberland," said Reimer, a professor in Oregon State's College of Agricultural Sciences.

In the paper, Reimer cites data that shows the average price of Douglas-fir logs between 2005 and 2020 was $631 per MBF (a forestry term for 1,000 board feet of lumber) of mill logs in southern Oregon. One board foot of lumber is 1 square foot and 1-inch thick.

Yet this average disguises a great deal of variation in price. From 2005 to 2020, the price ranged from $346 per MBF to $924 per MBF. The difference between the minimum and maximum was $578, nearly as large as the 15-year average price itself.

Since the paper was written, lumber prices have increased more, reaching the $1,000 per MBF range. The National Association of Home Builders recently released a report that said lumber prices have added an average of $24,000 to the cost of a new home.

"Right now log prices are phenomenally high," Reimer said. "It can feel like feast or famine in this industry but there is a logic that underlies the changes. The benefit of this paper is that we have identified a few pieces of readily observable information that allow people in the timber industry to make solid predictions about what will be happening in the next six months or so."

BOSTON - Men and women whose mothers experienced stressful events during pregnancy regulate stress differently in the brain 45 years later, results of a long-term study demonstrate.

In a unique sample of 40 men and 40 women followed from the womb into their mid-forties, the brain imaging study showed that exposure during fetal development to inflammation-promoting natural substances called cytokines, produced by mothers under negative stress, results in sex-associated differences in how the adult brain responds to negative stressful situations more than 45 years after birth, reports Jill M. Goldstein, PhD, founder and executive director of the Innovation Center on Sex Differences in Medicine (ICON) at Massachusetts General Hospital (MGH) and her co-authors.

The researchers found that abnormal levels of pro-inflammatory cytokines produced in mothers during pregnancy and the balance between pro-inflammatory and anti-inflammatory cytokines affect brain development differences by sex in their offspring that continue throughout life.

The findings are published in Proceedings of the National Academy of Sciences (PNAS).

"We know that there are developmental roots to major psychiatric disorders such as depression, schizophrenia and bipolar disorder, and we know that these roots begin in fetal development. We also know these disorders are associated with abnormalities in the brain circuitry that regulates stress--circuitry that is intimately tied to regulating our immune system," says Goldstein, a professor of Psychiatry and Medicine at Harvard Medical School. "Given that the stress circuitry consists of regions that develop differently in the male and female brain during particular periods of gestation and they function differently across our lifespans, we hypothesized that dysregulation of this circuitry in prenatal development would have lasting differential impact on the male and female brain in people with these disorders. We were particularly interested in the role of the immune system, in which some abnormalities are shared across these disorders."

Goldstein and colleagues used functional magnetic resonance imaging, which measures brain activity by showing differences in blood flow within and between different areas of the brain. The researchers found that exposure to pro-inflammatory cytokines in the womb was associated with sex differences in how areas of the brain are activated and communicate with one another under negative stressful conditions in midlife.

For example, they found that in both sexes, lower maternal levels of tumor necrosis factor-alpha (TNFα) a pro-inflammatory cytokine, were significantly associated with higher activity in the hypothalamus, a region of the brain that, among other functions, coordinates brain activity that regulates the release of stress hormones, like cortisol.

In contrast, lower levels of TNFα were also associated with more active communication between the hypothalamus and the anterior cingulate in men only. The anterior cingulate is an area of the brain associated with impulse control and emotion.

In women only, higher prenatal exposure to interleukin-6, another inflammatory cytokine, was associated with higher levels of activity in the hippocampus, a brain region important for inhibitory control of arousal.

Lastly, they found that the ratio between TNFα and the anti-inflammatory cytokine interleukin-10 was associated with sex-dependent effects on activity in the hypothalamus and its communication with the hippocampus, which provides inhibitory control of arousal in the hypothalamus under stress.

"Given that these psychiatric disorders are developing differently in the male and female brain, we should be thinking about sex-dependent targets for early therapeutic intervention and prevention," says Goldstein.

UNIVERSITY PARK, Pa. -- Approximately 40,000 children in the United States may have lost a parent to COVID-19 since February 2020, according to a statistical model created by a team of researchers. The researchers anticipate that without immediate interventions, the trauma from losing a parent could cast a shadow of mental health and economic problems well into the future for this vulnerable population.

In the researchers' model, for approximately every 13th COVID-related death, a child loses one parent. Children who lose a parent are at higher risk of a range of problems, including traumatic prolonged grief and depression, lower educational attainment, economic insecurity and accidental death or suicide, said Ashton Verdery, associate professor of sociology, demography and social data analytics and Institute for Computational and Data Sciences co-hire, Penn State.

"When we think of COVID-19 mortality, much of the conversation focuses on the fact that older adults are the populations at greatest risk. About 81% of deaths have been among those ages 65 and older according to the CDC (Centers for Disease Control and Prevention)," said Verdery, who is also an affiliate of the Population Research Institute at Penn State. "However, that leaves 19% of deaths among those under 65 -- 15% of deaths are among those in their 50s and early 60s and 3% are among those in their 40s. In these younger age groups, substantial numbers of people have children, for whom the loss of a parent is a potentially devastating challenge."

Three-quarters of the children who lost a parent are adolescents, but one quarter are elementary-aged children, Verdery said.

The statistics of parental death are grimmer for Black families, which have been disproportionately impacted by the pandemic, according to the researchers, who report their findings in today's (April 5) issue of JAMA Pediatrics. The team estimated that 20% of the children who lost a parent are Black even though only 14% of children in the U.S. are Black.

The model also suggests that parental deaths due to COVID-19 will increase the country's total cases of parental bereavement by 18% to 20% over what happens in a typical year, further straining an already stretched system that does not connect all children who are eligible to adequate resources.

Historical comparison

As a historical comparison, the number of children who lost a parent to COVID-19 is about 13 times the approximate 3,000 children who lost a parent in attacks of Sept. 11, 2001. After those attacks, the federal government initiated several programs to support the families of the victims.

Parentally bereaved children in the pandemic may face unique challenges. The social isolation, institutional strain and economic struggles caused by the pandemic may strain access to potential sources of support for children. Further, with many children out of schools and less connected to other family and community supports, suffering children may be less likely to be recognized.

"Teachers are such a vital resource in terms of identifying and helping at-risk children, and it is harder for them to do that when schools are operating remotely and teachers are so overburdened, making it vital to resume in-person instruction safely and support worn-out educators," Verdery said.

The researchers added that as pandemic deaths increase, that shadow of mental health and economic ills may only grow longer for children.

They suggest that equal -- or greater -- national efforts are needed to help children who have lost parents in the pandemic.

"I think the first thing we need to do is to proactively connect all children to the available supports they are entitled to, like Social Security child survivor benefits -- research shows only about half of eligible children are connected to these programs in normal circumstances, but that those who do fare much better," said Verdery. "We should also consider expanding eligibility to these resources. Second, a national effort to identify and provide counseling and related resources to all children who lose a parent is vital."

Research suggests that brief, evidence-based interventions delivered widely could help prevent severe psychological problems, although some children may need longer-term support.

Using kinship networks of white and Black individuals, drawn from demographic simulations, the researchers estimate the expected number of children ages 0 to 17 who would lose a parent to COVID-19, called the parental bereavement multiplier. The model suggested that .078 children aged 0 to 17 years old would be parentally bereaved for each COVID-19 related death, or about one for each 13 deaths. The team then used the multiplier to estimate the scope of parental bereavement based on various scenarios of COVID-19 casualty figures.

PHILADELPHIA-- Approximately 6.5 million people are under correctional supervision in the United States on any given day. Justice-involved individuals (people currently or recently in prison or jail, on probation or parole, or arrested) experience higher rates of substance use disorders than the general population. In fact, among people with opioid use disorder (OUD), more than half have reported contact with the criminal justice system.

Numerous clinical studies have shown that medications for OUD -- specifically, methadone or buprenorphine -- lead to superior outcomes for retention in treatment, reduced illicit opioid use, and decreased opioid-related overdose rates and serious acute care compared with treatments that rely on psychosocial interventions alone. However, due to a number of barriers, including access to health insurance, access to medications for OUD for those on parole, formerly incarcerated, or recently arrested remain significantly lower than the general population.

A new study published today in Health Affairs reveals that Medicaid expansion is associated with substantial improvements in access to medications for OUD for individuals referred to substance use treatment by criminal justice agencies. However, the study, led by Utsha Khatri, MD, an emergency medicine physician and a research fellow in the National Clinician Scholars Program and Perelman School of Medicine at the University of Pennsylvania, also reveals that individuals referred for treatment by the criminal justice system were substantially less likely to receive medications for OUD as part of the treatment plan when compared with those referred through all other sources.

"The response to substance use disorders in the United States has historically been criminalization. As a result, many individuals with OUD are involved with the criminal justice system, and this may influence their treatment prospects," says Khatri. "Any policy or intervention that seeks to mitigate the harms of risky substance use must also consider the impact among populations with criminal justice involvement specifically."

The study evaluated 10 years of data from the Treatment Episode Data Set-Admissions (TEDS-A), a national survey of substance treatment facility admissions conducted by the Substance Abuse and Mental Health Services Administration (SAMHSA). Researchers reviewed the data for a flag indicating that medications for OUD were part of the treatment plan during the admission.

The data revealed a total of 3,209,691 adults with OUD between 2008 and 2017. Of these, 21% were referred by a criminal justice agency - such as police, probation officers, judges, or prosecutors. It also showed that the proportion of people with OUD receiving medications as a part of their treatment increased substantially between 2008 and 2017 across all referral sources. Overall, though, individuals referred by these agencies were less likely to receive medications for OUD (MOUD) than were those referred by other sources during the study period, although this disparity narrowed slightly after Medicaid expansion: among people with OUD referred by a criminal justice agency, the proportion of people receiving MOUD increased from 6.3% in 2008 to 16.5% in 2017.

"Our study shows that Medicaid expansion is an important tool for expanding access to evidence-based care for people involved in the criminal justice system," says senior author Tyler Winkelman, MD, MSc, Co-Director of the Health, Homelessness, and Criminal Justice lab at the Hennepin Healthcare Research Institute and a clinician-investigator in the Division of General Internal Medicine at Hennepin Healthcare. "However, Medicaid alone will not entirely close gaps in care between people with and without criminal justice involvement. Additional work is needed to understand key drivers of the persistent disparities we identified."

Researchers say that there is room for improvement in addressing OUD treatment, both for people with and without criminal justice involvement. There is an abundance of data that consistently shows the use of methadone or buprenorphine is associated with reduced risk for overdose and opioid-related morbidity and mortality when compared with other treatment modalities, such as abstinence-only approaches, or behavioral interventions. However, incarceration-related stigma and preferences of criminal justice agencies might also influence the treatment plans among individuals with criminal justice involvement.

"Medicaid expansion improves evidence-based treatment for individuals with criminal justice involvement and OUD, and should be prioritized by states that have not yet expanded Medicaid," concludes Khatri, "However, additional policy changes, like unobstructed access to medications for OUD, are likely needed to reduce persistent treatment disparities."

PHILADELPHIA-- While the emergency department (ED) functions as an integral part of the United States healthcare safety net by handling all medical complaints regardless of insurance status, ED visits are expensive, and many are for lower-acuity conditions that may be amenable to care in other settings. Previous research has suggested that greater availability of urgent care centers - freestanding facilities with extended hours that staff emergency physicians, primary care physicians, or nurse practitioners, and focus on a broad range of lower acuity complaints, like rash, muscle strain, bronchitis, and urinary tract infection - helps decrease ED visits, but whether the centers reduce or increase net spending for patients and insurers has yet to be determined.

A study published today in Health Affairs documents for the first time that urgent care centers are associated with increased spending for lower-acuity visits across EDs and urgent care centers. Urgent care centers increase the number of people seeking care. For every 37 urgent care visits, one fewer lower acuity ED visit occurs. Urgent care centers increase access, but pose risks for health insurers and patients who must pay these increased costs.

"Previous studies have used different approaches to show that urgent care centers reduce emergency department visits for lower acuity conditions," says senior author Ari Friedman, MD, PhD, an assistant professor of Emergency Medicine, Medical Ethics and Health Policy in the Perelman School of Medicine at the University of Pennsylvania. "Our findings confirm ED visits go down, but then show that total costs across both settings actually go up, not down."

Researchers conducted analyses using a claims database with more than twenty million patients per year covered by a national managed care plan from January 1, 2008, to December 31, 2019, spanning all fifty states. They assessed how the number of lower acuity ED visits changed when an urgent care center visit occurred within each ZIP code.

Across the twelve years of the study period, researchers found that by 2019, the opening of an urgent care center led to a decline in the number of lower acuity ED visits, and that these ED visits were approximately ten times more expensive than urgent care center visits. Researchers found that the substitution ratio (the number of urgent care visits needed to deter a single ED visit) was high: an increase of 37 urgent care center visits was associated with the substitution of a single lower-acuity ED visit. While urgent care center visits are less expensive than ED visits, it's not enough to offset this difference. Each $1,646 lower-acuity ED visit prevented was offset by a $6,327 increase in urgent care center costs.

First author Bill Wang notes, "We expected urgent care centers to increase access and decrease emergency department visits, but we were surprised by just how many urgent care visits it took to substitute for a lower acuity ED visit."

Friedman points out that cost saving shouldn't be the only factor considered when determining where and how to access care. "We should evaluate new care models and interventions on the same standard as we evaluate new drugs - do they improve lives more than they increase costs? That's the important metric. But the cost increases here are so large that the value side of the equation would have to do a lot of work to make it pay off."

The authors note that the possibility remains that the availability of urgent care centers in a market, when combined with other interventions - like telemedicine, primary care, or changes to benefits - could be effective in augmenting the substitution ratio.

Beyond access, the clinical benefit of these additional visits to unscheduled care requires further research, as does the impact and role of telemedicine, says Friedman. "We're watching the field with interest."

What The Study Did: Researchers estimated and projected the number of children in the United States affected by the death of a parent from COVID-19.

Authors: Rachel Kidman, Ph.D., of Stony Brook University in Stony Brook, New York, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamapediatrics.2021.0161)

Editor's Note: The article includes conflict of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

An interdisciplinary team led by KU Leuven and Stanford has identified 76 overlapping genetic locations that shape both our face and our brain. What the researchers didn't find is evidence that this genetic overlap also predicts someone's behavioural-cognitive traits or risk of conditions such as Alzheimer's disease. This means that the findings help to debunk several persistent pseudoscientific claims about what our face reveals about us.

There were already indications of a genetic link between the shape of our face and that of our brain, says Professor Peter Claes from the Laboratory for Imaging Genetics at KU Leuven, who is the joint senior author of the study with Professor Joanna Wysocka from the Stanford University School of Medicine. "But our knowledge on this link was based on model organism research and clinical knowledge of extremely rare conditions," Claes continues. "We set out to map the genetic link between individuals' face and brain shape much more broadly, and for commonly occurring genetic variation in the larger, non-clinical population."

Brain scans and DNA from the UK Biobank

To study genetic underpinnings of brain shape, the team applied a methodology that Peter Claes and his colleagues had already used in the past to identify genes that determine the shape of our face. Claes: "In these previous studies, we analysed 3D images of faces and linked several data points on these faces to genetic information to find correlations." This way, the researchers were able to identify various genes that shape our face.

For the current study, the team relied on these previously acquired insights as well as the data available in the UK Biobank, a database from which they used the MRI brain scans and genetic information of 20,000 individuals. Claes: "To be able to analyse the MRI scans, we had to measure the brains shown on the scans. Our specific focus was on variations in the folded external surface of the brain - the typical 'walnut shape'. We then went on to link the data from the image analyses to the available genetic information. This way, we identified 472 genomic locations that have an impact on the shape of our brain. 351 of these locations have never been reported before. To our surprise, we found that as many as 76 genomic locations predictive of the brain shape had previously already been found to be linked to the face shape. This makes the genetic link between face and brain shape a convincing one."

The team also found evidence that genetic signals that influence both brain and face shape are enriched in the regions of the genome that regulate gene activity during embryogenesis, either in facial progenitor cells or in the developing brain. This makes sense, Wysocka explains, as the development of the brain and the face are coordinated. "But we did not expect that this developmental cross-talk would be so genetically complex and would have such a broad impact on human variation."

No genetic link with behaviour or neuropsychiatric disorders

At least as important is what the researchers did not find, says Dr Sahin Naqvi from the Stanford University School of Medicine, who is the first author of this study. "We found a clear genetic link between someone's face and their brain shape, but this overlap is almost completely unrelated to that individual's behavioural-cognitive traits."

Concretely: even with advanced technologies, it is impossible to predict someone's behaviour based on their facial features. Peter Claes continues: "Our results confirm that there is no genetic evidence for a link between someone's face and that individual's behaviour. Therefore, we explicitly dissociate ourselves from pseudoscientific claims to the contrary. For instance, some people claim that they can detect aggressive tendencies in faces by means of artificial intelligence. Not only are such projects completely unethical, they also lack a scientific foundation."

In their study, the authors also briefly address conditions such as Alzheimer's, schizophrenia, and bipolar disorder. Claes: "As a starting point, we used the results that were previously published by other teams about the genetic basis of such neuropsychiatric disorders. The possible link with the genes that determine the shape of our face had never been examined before. If you compare existing findings with our new ones, you see a relatively large overlap between the genetic variants that contribute to specific neuropsychiatric disorders and those that play a role in the shape of our brain, but not for those that contribute to our face." In other words: our risk of developing a neuropsychiatric disorder is not written on our face either.