Culture

Patients paying for unproven IVF add-on treatments

1 July 2021: Despite only limited evidence that fertility add-ons increase the odds of having a baby, the majority of women (82%) have used one or more of these treatments as part of their IVF.

This is the conclusion of a retrospective study of 1,590 Australian patients which also found more than seven in 10 (72%) had incurred additional costs for these unproven additional therapies and techniques which range from Chinese herbal medicine to endometrial scratching.

The results based on an online survey into prevalence of these optional extras will be presented today by principal investigator Dr Sarah Lensen, a researcher from the University of Melbourne, Australia, at the 37th virtual Annual Meeting of ESHRE.

The findings, says Lensen, suggest that patients "may not be adequately informed" about the lack of evidence to support "the effectiveness and safety of add-ons". She adds that "accessible and transparent information" is needed - and large high-quality randomised trials - to help women make decisions and minimise the regret felt by those whose IVF has been unsuccessful.

This report into add-ons is based on a questionnaire advertised on Facebook, distributed to women undergoing IVF, and completed between June and July 2020. Gestational surrogates or patients who used a surrogate were excluded as were those who donated eggs or underwent elective egg freezing.

Participants were asked about their IVF and medical history, and details about add-on use over the past 3.5 years including specific treatments and cost. They were also questioned about what importance they placed on evidence around safety and effectiveness.

In addition to cost and prevalence of add-ons, the results showed that the most commonly used of these optional extras was acupuncture (45%) followed by preimplantation genetic testing for aneuploidy (PGT-A) (28%) then Chinese herbal medicine (26%).

The cost associated with some of the add-ons used such as aspirin and heparin, says Lensen, is likely to be negligible. However, she points out that expenses are likely to be "significant" for PGT-A, or for repeated add-on treatments over multiple cycles.

Overall, relatively few (18%) women using add-on fertility treatments reported that they first raised the issue, with more than half (54%) saying they had first heard about them from their fertility specialist. The majority (71%) said their specialist generally raised add-on options during consultations.

What also emerged from the study is that women placed significant importance on scientific evidence supporting the use of add-ons. More than half (55%) scored over 90 (out of 100) that they think it's important there is evidence that add-ons improve live birth rates, and 73% gave the same score for their use being safe. This is despite associations to the contrary, says Lensen, as most add-ons are not supported by evidence that they increase live birth rates (LBRs), and some such as immune therapies have been linked with low birth weight and other issues.

Around a third (30%) of women experienced moderate to severe regret about using add-ons compared with 34% who had no regret at all. The level of misgivings about their decision was higher in women who had not conceived or achieved a live birth. In addition, those who reported their fertility specialist had more than 50% input into their decision to use an add-on had more regret than those whose doctor had a lesser role.

The study results come at a time when adjunct treatments are under increasing scrutiny. UK regulator the Human Fertilisation and Embryology Authority (HFEA) has introduced a traffic light system to rate add-ons but none has been awarded a green signal.

The use of some adjunct therapies, says Lensen, is likely to be "associated with a significant financial burden" and may even "potentially pose risk to patient." Therefore, she says impartial evidence-based information like the HFEA's should be available in other countries.

Credit: 
European Society of Human Reproduction and Embryology

Older patients with heart failure denied effective treatments

Sophia Antipolis - 1 July 2021: Heart failure patients aged 80 and above are less likely to receive recommended therapies and dosages compared to their younger counterparts, according to research presented today at Heart Failure 2021, an online scientific congress of the European Society of Cardiology (ESC).1

"Guidelines recommend the same treatments for all heart failure patients regardless of age," said study author Dr. Davide Stolfo of the Karolinska Institute, Stockholm, Sweden.2 "Our analysis adjusted for other conditions that might justify withholding therapy or reducing the dose - for example impaired kidney function - and age was independently associated with undertreatment."

The study investigated the prescription of evidence-based therapy in patients with heart failure according to three age categories: under 70, 70 to 79, and 80 years or older. The analysis was limited to heart failure with reduced ejection fraction since it is the only subtype with treatments proven to benefit prognosis. The researchers used data from the nationwide Swedish Heart Failure Registry linked with other national registries in 2000 to 2018.

The study included 27,430 patients with heart failure. The average age was 74 years and 27% were women. Regarding the age categories, 31% were under 70, 34% were 70 to 79, and 35% were 80 years or above. Patients in the oldest age category were more likely to be women than men, and had more severe heart failure and more co-existing conditions compared to the other age groups.

Prescription of treatments progressively decreased with increasing age. Regarding medications, RASi (renin angiotensin system inhibitor)/ARNi (angiotensin receptor neprilysin inhibitor), beta-blockers, and MRA (mineralocorticoid receptor antagonist), respectively, were prescribed in 95%, 95% and 54% in patients aged under 70? 90%, 93% and 47% in patients aged 70 to 79; and 80%, 88% and 35% in those aged 80 or above.

Regarding device therapies, the use of implantable cardioverter defibrillators (ICDs) and cardiac resynchronisation therapy (CRT), respectively, among eligible patients was 22% and 50% in patients under 70; 17% and 42% in the 70 to 79 group; and 5% and 23% in those aged 80 or above.

Patients aged 80 or above were also less likely to be treated with the recommended dose of medications or to receive all three recommended types of medications (RASi/ARNI, beta-blocker and MRA). Half of those under 70 met both recommendations compared to just 42% of the 70 to 79 age group, and 26% of those aged 80 or above.

The researchers analysed the association of age with the prescription of each medication and device, and the use of recommended doses. The analysis was extensively adjusted for other conditions including diabetes, previous cancer, kidney function, low blood pressure and anaemia. With the exception of CRT, age was independently and inversely associated with the odds of receiving recommended treatments and dosages.

Dr. Stolfo said: "Our analysis shows that even after statistical adjustment for many other variables included in the registries, nearly all treatments are underused in older patients. This was an observational study so it is not possible to determine the reasons, but one possibility is that clinicians believe treatments are less effective in older people with heart failure."

Dr. Stolfo noted that older patients, particularly those with co-existing conditions, are often excluded from clinical trials. He said: "Studies in older age groups with heart failure are needed to provide clinicians with greater certainty about the effectiveness of full-dose treatment. We should follow the example of a study investigating this question according to gender, which suggested that women with heart failure might need lower doses of some medications than men."3

He concluded: "In younger patients with heart failure, the primary goal of treatment is to improve survival, while in older patients we aim to reduce symptoms, improve quality of life and prevent hospitalisations. Strategies are needed to ensure that all patients with heart failure are optimally treated."

Credit: 
European Society of Cardiology

Why are some fish warm-blooded? Predatory sharks gain speed advantage

image: A tiger shark (Galeocerdo cuvier) swimming at the surface with a biologging package attached to dorsal fin. This package records temperature, swimming speed, depth, body movement and video footage.

Image: 
Diego Camejo (Beneath the Waves).

New research from marine biologists offers answers to a fundamental puzzle that had until now remained unsolved: why are some fish warm-blooded when most are not?

It turns out that while (warm-blooded) fish able to regulate their own body temperatures can swim faster, they do not live in waters spanning a broader range of temperatures.

The research therefore provides some of the first direct evidence as to the evolutionary advantage of being warm-blooded as well as underlining that species in this demographic - such as the infamous white shark and the speedy bluefin tuna - are likely just as vulnerable to changing global ocean temperatures as their cold-blooded relatives.

Lucy Harding, PhD Candidate in Trinity College Dublin's School of Natural Sciences, is the first author of the associated research article, which has just been published in the journal, Functional Ecology. She said:

"Scientists have long known that not all fish are cold-blooded. Some have evolved the ability to warm parts of their bodies so that they can stay warmer than the water around them, but it has remained unclear what advantages this ability provided.

"Some believed being warm-blooded allowed them to swim faster, as warmer muscles tend to be more powerful, while others believed it allowed them to live in a broader range of temperatures and therefore be more resilient to the effects of ocean warming as a result of climate change."

Lucy and her international team of collaborators assessed these two possibilities by collecting data from wild sharks and bony fish, as well as using existing databases.

By attaching biologging devices to the fins of the animals they caught, they were able to collect information such as water temperatures encountered by the fish in their habitats; the speeds at which the fish swam for most of the day; and the depths of water the fish swam in.

The results showed that warm-blooded fishes swim approximately 1.6 times faster than their cold-blooded relatives, but they did not live in broader temperature ranges.

Nick Payne, Assistant Professor in Zoology in Trinity's School of Natural Sciences, said:

"The faster swimming speeds of the warm-blooded fishes likely gives them competitive advantages when it comes to things like predation and migration. With predation in mind, the hunting abilities of the white shark and bluefin tuna help paint a picture of why this ability might offer a competitive advantage.

"Additionally, and contrary to some previous studies and opinions, our work shows these animals do not live in broader temperature ranges, which implies that they may be equally at risk from the negative impacts of ocean warming. Findings like these - while interesting on their own - are very important as they can aid future conservation efforts for these threatened animals."

Credit: 
Trinity College Dublin

Leaders' pandemic policies engendered varying levels of trust

As the COVID-19 pandemic exploded across the globe in early 2020, the world's leaders were faced with a flurry of tough moral dilemmas. Should schools and businesses shut down, and if so, for how long? Who should receive scarce resources, such as ventilators, when there wouldn't be enough for everyone? Should people be required to practice contact tracing to control the spread of infection? Should life-saving medicine be held for a country's own citizens or shared with those in greater need?

Some global leaders advocated for a utilitarian approach to these dilemmas: impartially maximizing the greatest good for the greatest number of people, even if that would come at the cost of harming a minority of the population. Utilitarianism, however, is a controversial way of making moral decisions and those who use this approach might not be viewed as trustworthy.

In a new study, Molly Crockett, an associate professor of psychology at Yale, examined whether people trust leaders who make utilitarian decisions during a pandemic. To find out, she and her co-first authors -- Yale's Clara Colombatto and the University of Kent's Jim Everett -- assembled a multidisciplinary team of 37 international researchers to study people's trust in leaders around the globe. In a series of online experiments conducted as cases surged late in 2020, the team asked nearly 24,000 people in 22 countries whether the endorsement or rejection of utilitarian policies impacted their trust in leaders.

The results, published July 1 in the journal Nature Human Behavior, show people had a nuanced view when judging the policy decisions of leaders. People tended to trust utilitarian leaders who sought to save the most lives around the globe, rather than favoring their own citizens. But they were far less willing to trust those whose policy decisions would sacrifice the well-being of some for the benefit of others.

For instance, a shortage of ventilators led some leaders to propose reserving them for younger people more likely to survive a severe case of COVID-19. People tended to distrust leaders who accepted this form of utilitarianism, known as instrumental harm. However, they bestowed more trust in those who would share scarce medicine in regions globally where it is most needed, an aspect of utilitarianism called impartial beneficence.

The results were consistent across the countries studied, which included Australia, Brazil, Canada, Chile, China, Denmark, France, Germany, India, Israel, Italy, the Kingdom of Saudi Arabia, Mexico, the Netherlands, Norway, Singapore, South Africa, South Korea, Spain, the United Arab Emirates, the United Kingdom, and the United States of America.

These patterns held regardless of whether or not people personally agreed with the leader's policy decision. "People do prefer leaders who agree with them on policies, but even after we control for individual policy preferences, people generally trust leaders who endorse impartial beneficence and distrust leaders who accept instrumental harm," said Colombatto, a Ph.D. student in the Department of Psychology.

Everett concluded, "When communicating during a crisis, leaders should be aware that utilitarian approaches to moral dilemmas can both erode and enhance trust -- even when the leaders themselves doesn't have the power to resolve them."

Pandemic choices: Do you trust leaders who make these?

Researchers asked almost 24,000 people in 22 countries to read about moral dilemmas leaders faced during the COVID-19 pandemic. Two examples of those tough moral choices are below. After learning about the leaders' decisions, respondents were asked to rate how trustworthy they thought those leaders were, and to make decisions about whether to trust each leader with control of a group's financial resources. Subjects were also asked whether they would vote for a leader who took a particular policy position.

A demonstration of the trust rating survey is available here:

https://yalesurvey.ca1.qualtrics.com/jfe/form/SV_ekzXerwo4NHMzyK

Medicine Dilemma

Non-Utilitarian Leader

Imagine that the mayor of a major city in your region is arguing that U.S.-made medicine should be reserved for treating American citizens.

This mayor said, "We have a right to use our own resources to help our own citizens before everyone else. Other countries can produce their own treatments for COVID-19."

Average self-reported trust: 3.93 out of 7; votes: 38.93%

Utilitarian Leader

Imagine that the mayor of a major city in your region is arguing that U.S.-made medicine should be given to whoever needs it most, even if that means sending it to other countries.

This mayor said, "COVID-19 is a global pandemic that affects all humans equally. We need to be impartial and send treatment where it can achieve the greatest good."

Average self-reported trust: 4.57 out of 7; votes: 61.07%

Ventilators Dilemma

Non-Utilitarian Leader

Imagine that the mayor of a major city in your region is arguing that doctors should give everyone equal access to COVID treatment.

This mayor said, :It's not our place to choose who lives. Everyone has the same right to receive equal access to treatment, and we cannot abandon our most vulnerable in an effort to save more lives."

Average self-reported trust: 5.41 out of 7; votes: 85.15%

Utilitarian Leader

Imagine that the mayor of a major city in your region is arguing that younger and healthier people should be prioritized for COVID treatment.

This mayor said, "We have to think about how we can do the most good with the resources we have, and that means prioritizing those people who have the best chance of recovering and living a long and healthy life."

Average self-reported trust: 2.97 out of 7; votes: 14.85%

Credit: 
Yale University

Discovery of nanosized molecules that might inhibit Alzheimer's and Parkinson's diseases

image: Illustration of molecules of polyoxoniobate Nb10 and TiNb9

Image: 
Mark Rambaran

Nanosized molecules of a particular chemical element can inhibit the formation of plaque in the brain tissues. This new discovery by researchers at Umeå University, Sweden, in collaboration with researchers in Croatia and Lithuania, provides renewed hope for novel treatments of, for instance, Alzheimer's and Parkinson's disease in the long run.

"This is indeed a very important step that may form the basis of new and efficient treatments of neurodegenerative diseases in the future," says Professor Ludmilla Morozova-Roche at Umeå University.

When proteins misfold they form insoluble fibrils called amyloids, which are involved in several serious diseases such as Alzheimer's and Parkinson's, Corino de Andrade's and the mad cow disease. Amyloid aggregates kill neuronal cells and form amyloid plaques in the brain tissues.

What researchers in Umeå in Sweden, Vilnius in Lithuania and Rijeka in Croatia have discovered is that a particular nanosized molecules can hinder the amyloid formation of pro-inflammatory protein S100A9. These molecules are able even to dissolve already pre-formed amyloids, which has been shown by using atomic force microscopy and fluorescence techniques. The molecules in question are nanosized polyoxoniobates, which is so-called polyoxometalate ions with a negative charge containing the chemical element niobium.

"Further research is needed before we can safely say that functioning treatments can be derived from this, but the results so far have proven very promising," says Ludmilla Morozova-Roche.

The researchers have been working with two different polyoxoniobate molecules, Nb10 and TiNb9. Both turned out to inhibit SI00A9 amyloids by forming ionic interactions with the positively charged patches on the protein surface, which are critical for amyloid self-assembly. The polyoxoniobate molecules that have been studied are relatively chemically stable and water-soluble. The molecules are nanosized, which means that they are extremely small. These nanomolecules can also be of interest for other medical applications such as implants thanks to their high biocompatibility and stability.

At Umeå University, two research groups, from the Faculty of Medicine and the Department of Chemistry, have collaborated by addressing the issue from different angles and by applying a wide spectrum of biophysical and biochemical techniques and through molecular dynamics simulations.

Credit: 
Umea University

Forget cash! Credit is key to the survival of busking

Economists at RMIT University in Melbourne, Australia, economists found passers-by often donated more when paying via a digital platforms like apps, QR codes, PayPal and even Bitcoin, compared to the centuries' old payment method of loose coins.

Using data from the online platform The Busking Project, the study analysed individual payments to over three and half thousand active buskers from 121 countries to predict the characteristics of performers who were more likely to receive online donations.

The study found North America and Europe were home to the most active buskers and audiences on the platform, with buskers registered in the UK and USA having significantly higher prospects of receiving a donations.

The study also found:

Circus performers received the biggest donations;

Musicians were most likely to receive donations, but received smaller amounts compared to other types of artists;

The number of other onlookers influenced if and how much passers-by donated;

The artist's location and social media profile also impacted and influenced receiving a donation

Artists who joined the platform after the World Health Organisation (WHO) announcement that COVID-19 was a pandemic in March 2020 were more likely to receive a donation, which ranged from US$1 to over US$500 and averaged at just over US$14.

Lead author Dr Meg Elkins said street performers had a critical role to play as cities looked to bring back the buzz to their CBDs in the wake of the COVID-19 pandemic.

"Buskers often exist on the cultural fringes and get little, if any funding, but can bring vibrancy to streets, squares and shopping strips as people walk from the train to their office or duck out during their lunch hour," Elkins said.

"Europe and America have well-established busking cultures from Covent Gardens in London, Mauerpark in Berlin, to the many and varied roving performers in New York's Washington Square Park and subway stations, and this time of year when the northern summer is beginning is when it's often at its finest.

"Buskers performing in public for coin is a centuries old practice, but they have to move online as our society becomes increasingly cashless.

"We know many street performers become personalities in their own right and we wanted to uncover how they could use digital payment systems to increase their online earnings and create more sustainable careers.

"Circus performers being more likely to attract online donations might be because they're better at incorporating that 'hat line' into their performance compared to musicians who are traditionally much more static."

Elkins, a Senior Lecturer in the School of Economics, Finance and Marketing at RMIT University and its the Behavioural Business Lab, said the findings were important as artists and the creative and cultural industries had to become more entrepreneurial to survive.

"In the future, we could see QR codes as part of the street performance, which would simplify the payment process even further," she said.

"More than 40 QR code trails are underway across Europe, the US and Australia.

"Digital platforms can potentially allow street performers to generate more generous donations beyond cash tips.

"They're also a great way for artists to interact with supporters and build that all important fan base, which can ultimately help sustain a career."

Credit: 
RMIT University

Closing the gap on the missing lithium

image: As a beam of beryllium comes in from the left, the deuteron Trojan horse intercepts it at the target and delivers its neutron soldier. This allows the decay products of the beryllium and neutron reactions to be captured by a curved array of six detectors on the right.

Image: 
©2021 Hayakawa et al.

There is a significant discrepancy between theoretical and observed amounts of lithium in our universe. This is known as the cosmological lithium problem, and it has plagued cosmologists for decades. Now, researchers have reduced this discrepancy by around 10%, thanks to a new experiment on the nuclear processes responsible for the creation of lithium. This research could point the way to a more complete understanding of the early universe.

There is a famous saying that, "In theory, theory and practice are the same. In practice, they are not." This holds true in every academic domain, but it's especially common in cosmology, the study of the entire universe, where what we think we should see and what we really see doesn't always match up. This is largely because many cosmological phenomena are difficult to study due to inaccessibility. Cosmological phenomena are usually out of our reach because of the extreme distances involved, or often they have occurred before the human brain had even evolved to worry about them in the first place -- such is the case with the big bang.

Project Assistant Professor Seiya Hayakawa and Lecturer Hidetoshi Yamaguchi from the Center for Nuclear Study at the University of Tokyo, and their international team are especially interested in one area of cosmology where theory and observation are very misaligned, and that is the issue of the missing lithium, the cosmological lithium problem (CLP). In a nutshell, theory predicts that in the minutes following the big bang that created all matter in the cosmos, there should be an abundance of lithium around three times greater than what we actually observe. But Hayakawa and his team accounted for some of this discrepancy and have thus paved the way for research that may one day resolve it entirely.

"13.7 billion years ago, as matter coalesced from the energy of the big bang, common light elements we all recognize -- hydrogen, helium, lithium and beryllium -- formed in a process we call Big Bang nucleosynthesis (BBN)," said Hayakawa. "However, BBN is not a straightforward chain of events where one thing becomes another in sequence; it is actually a complex web of processes where a jumble of protons and neutrons builds up atomic nuclei, and some of these decay into other nuclei. For example, the abundance of one form of lithium, or isotope -- lithium-7 -- mostly results from the production and decay of beryllium-7. But it has either been overestimated in theory, underobserved in reality, or a combination of the two. This needs to be resolved in order to really understand what took place way back then."

Lithium-7 is the most common isotope of lithium, accounting for 92.5% of all observed. However, even though the accepted models of BBN predict the relative amounts of all elements involved in BBN with extreme accuracy, the expected amount of lithium-7 is around three times greater than what is actually observed. This means there is a gap in our knowledge about the formation of the early universe. There are several theoretical and observational approaches which aim to resolve this, but Hayakawa and his team simulated conditions during BBN using particle beams, detectors and an observational method known as the Trojan horse.

"We scrutinized more than ever before one of the BBN reactions, where beryllium-7 and a neutron decay into lithium-7 and a proton. The resulting levels of lithium-7 abundance were slightly lower than anticipated, about 10% lower," said Hayakawa. "This is a very difficult reaction to observe since beryllium-7 and neutrons are unstable. So we used deuteron, a hydrogen nucleus with an extra neutron, as a vessel to smuggle a neutron into a beryllium-7 beam without disturbing it. This is a unique technique, developed by an Italian group we collaborate with, in which the deuteron is like the Trojan horse in Greek myth, and the neutron is the soldier who sneaks into the impregnable city of Troy without tipping off the guards (destabilizing the sample). Thanks to the new experimental result, we can offer future theoretical researchers a slightly less daunting task when trying to resolve the CLP."

Credit: 
University of Tokyo

Study with healthcare workers supports that immunity to SARS-CoV-2 is long-lasting

One year after infection by SARS-CoV-2, most people maintain anti-Spike antibodies regardless of the severity of their symptoms, according to a study with healthcare workers co-led by the Barcelona Institute for Global Health (ISGlobal), the Catalan Health Institute (ICS) and the Jordi Gol Institute (IDIAP JG), with the collaboration of the Daniel Bravo Andreu Private Foundation. The results suggest that vaccine-generated immunity will also be long-lasting.

One of the key questions to better predict the pandemic's evolution is the duration of natural immunity. A growing number of studies suggest that most people generate a humoral (antibody) and cellular (T cells) response that is maintained during several months, maybe years.

During the first wave of the pandemic, the team at ICS/IDIAP JG in collaboration with Carlota Dobaño's team at ISGlobal started a follow-up study of a cohort of healthcare workers with COVID-19 - a total of 173 people working in healthcare centers of central Catalonia. Most infections were mild to moderate, although some cases required hospitalization.

The research team took regular blood samples from September 2020 onwards to measure the level and type of SARS-CoV-2-specific antibodies in these patients. This work was possible thanks to the support of the Daniel Bravo Foundation, which equipped ISGlobal with the latest technology and necessary resources to perform the study and rapidly reach conclusions during the subsequent waves.

"The results obtained until now lead us to believe that immunity to SARS-CoV-2 will last longer than we originally thought. Being a new virus, it is very important to understand how it behaves and affects different people", says Anna Ruiz Comellas, researcher at the Catalan Institute of Health and co-author of the study.

No significant decay in antibody levels was observed over the first five months, and at 9 months, 92.4% of peoples remained seropositive - 90% of them had IgG, 76% had IgA and 61% had IgM recognising the Spike protein or the receptor binding domain (RBD). The results were similar among healthcare workers who had not been vaccinated in April (95% had IgG, 83% IgA and 25% IgM).

"These data confirm that IgG have a longer duration, but IgM levels, which are supposed to last less, were unexpectedly quite sustained over time," says Gemma Moncunill, ISGlobal researcher and senior co-author of the study, together with Ruíz-Comellas. Hospitalization, fever, and loss of smell and taste were associated with higher antibody levels at five or nine months.

Four reinfections were observed among the participants. Two of them were symptomatic and occurred in seronegative individuals. Another asymptomatic reinfection occurred in a subject with very low antibody levels. These results indicate that anti-Spike antibodies protect against symptomatic infections. "They also indicate that people who have not been previously infected should be prioritised for vaccination, since those who have already been infected may be protected for at least one year," says Anna Ramírez-Morros, first co-author of the study.

"Considering that antibody levels achieved upon vaccination are usually higher than those generated upon natural infection, our results suggest that vaccine-induced immunity will also be long-lasting," concludes Carlota Dobaño.

Credit: 
Barcelona Institute for Global Health (ISGlobal)

Eruption of the Laacher See volcano redated

image: 13,000-year-old tree trunk from the volcanic deposits of the Laacher See eruption in the vicinity of Miesenheim, Germany.

Image: 
photo/©: Olaf Jöris

The eruption of the Laacher See volcano in the Eifel, a low mountain range in western Germany, is one of Central Europe's largest eruptions over the past 100,000 years. The eruption ejected around 20 cubic kilometers of tephra and the eruption column is believed to have reached at least 20 kilometers in height, comparable to the Pinatubo eruption in the Philippines in 1991. Technical advances in combination with tree remains buried in the course of the eruption now enabled an international research team to accurately date the event. Accordingly, the eruption of the Laacher See volcano occurred 13,077 years ago and thus 126 years earlier than previously assumed. This sheds new light on the climate history of the entire North Atlantic and European region and requires an adaptation of the European climate archives. "We can now precisely date a drop in temperature at the end of the last glacial period, so that the information coincides with that observed from the Greenland Ice Sheet cores," said Dr. Frederick Reinig, a dendrochronologist at Johannes Gutenberg University in Mainz (JGU). An international research team with experts in archeology, climatology, ecology, radiocarbon dating, and volcanology was involved in this study. The research results were published in the renowned scientific journal Nature.

Charred remains of birch and poplar wood have been preserved to this day

The eruption of the Laacher See volcano was a natural disaster that affected large parts of Europe. The ash rain reached as far as northern Italy in the south and Saint Petersburg in the Northeast. In the immediate vicinity and the neighboring Rhine Valley, mighty deposits of ash and pumice formed, which buried all life beneath them. "During the eruption, pyroclastic flows buried the local vegetation around the Laacher See volcano. The trees were partially charred within the ash deposits and have been preserved to this day," explained Reinig, describing the eruption process that took place over several weeks in late spring to early summer and which now enables scientists to precisely date the event. "These wooden contemporary witnesses are very rare, and they are difficult to recover," said Reinig, first author of the study.

"The regional effects of the volcanic eruption have been well studied. What we have been missing so far is the certainty of when exactly this happened," emphasized Professor Ulf Büntgen, co-author of the Nature publication from the University of Cambridge. This was now determined based on samples from buried birch and poplar trees.

The analysis of tree rings reveals the precise date of the eruption

The volcanic sediments not only preserved the wood for over 13,000 years but also allowed to identify the individual tree rings. "The tree rings enable us to exactly determine the age of the samples," said Professor Jan Esper from Mainz University. In a joint initiative of the Federal Research Institute for Forests, Snow and Landscape WSL in Birmensdorf, Switzerland, together with the Archaeological Research Center and Museum for Human Behavioral Evolution MONREPOS in Neuwied, both newly discovered samples and older finds were analyzed. For this purpose, the Laboratory for Ion Beam Physics at ETH Zurich carried out radiocarbon measurements on 157 individual tree rings of the examined trees. Calibration of these results against a Swiss reference chronology then resulted in the precise dating. "The constant advances in radiocarbon measurement technology and the calibration methods used, as well as the careful handling of the sensitive samples, were the key to establish this dating with an uncertainty of less than ten years," said Lukas Wacker from ETH Zurich.

Revised dating of the volcanic eruption has consequences for the synchronization of European climate archives and the understanding of large-scale climate dynamics

According to the description in Nature, the eruption of the Laacher See volcano took place 13,006 years before 1950, with an uncertainty of nine years. That is 126 years earlier than the generally accepted dating based on sediments in the Meerfelder Maar from the Eifel region in Germany.

This difference has far-reaching consequences for the synchronization of European climate archives and the understanding of North Atlantic and European climate history. Laacher See eruption ashes were widespread over large areas of Central and Northern Europe as a result of the volcanic eruption and represent an important time marker for paleoenvironmental archives. Due to the new dating, the European archives now have to be temporally adapted. At the same time, a previously existing temporal difference to the data from the Greenland ice cores was closed.

This means that the massive cooling at the beginning of the Younger Dryas - i.e., the last Ice Age intermezzo lasting around 1,300 years before the currently prevailing warm phase, the Holocene - also occurred in Central Europe 130 years earlier, around 12,870 years ago respectively. This is in line with the onset of the cooling in the North Atlantic region identified in ice cores from Greenland. During the Younger Dryas period, temperatures in Central Europe fell by up to 5 degrees Celsius. This strong cooling did not take place time transgressively, as previously thought, but rather synchronously over the entire North Atlantic and Central European region," said Frederick Reinig. The results of the interdisciplinary research team not only set a precise date for the eruption of the Laacher See in the Eifel. The revised age of the ash deposits and the associated shift in the European climate archives now sheds new light on the climate history of the entire North Atlantic region.

Credit: 
Johannes Gutenberg Universitaet Mainz

Extracellular matrix guides growth and function of epithelial cells

image: Microscopy image of mammary epithelium of a pregnant mouse, which has Lama5 gene deleted from the luminal epithelial cells (green: epithelial cell junctions, red: laminin, blue: nuclei).

Image: 
Johanna Englund

Scientists at the University of Helsinki have found an essential factor from the extracellular matrix that regulates functionality of the breast tissue for instance during pregnancy.

Extracellular matrix (ECM) has previously been recognised as an important element for the growth of various epithelial cells, but rather as a scaffold. A new study shows that ECM can also regulate the function of epithelial cells.

Our tissues constitute of differentiated cell types, which perform specific tasks that are tightly controlled. Normal growth and functioning of tissues is possible only when the various differentiated cell types interact appropriately. Differentiation and function of breast epithelium is guided by a group of cells responsive for estrogen and progesterone hormones. In the recent study it was found that these cells produce an ECM protein into their surroundings, and it regulates the growth and differentiation of the epithelium from outside the cells. Especially, the production of this protein, Lama5, was found to strengthen the functionality of these cells.

Hormone responsive cells can sense growth signals, such as cues from hormones and growth factors, and relay them into neighboring cells. When Lama5 gene was deleted from these cells, they became unable to relay these signals and halted the growth of the entire epithelium.

"This study shows that the extracellular environment produced by the cells themselves is an important factor for the identity and function of epithelial cells, and therefore for the whole tissue", says assistant professor Pekka Katajisto from University of Helsinki. The study was conducted in his laboratory.

Development during pregnancy and milk production is impaired

Hormone responsive cells were previously not known to participate in generating the surrounding ECM or even having ECM contacts.

"We observed that surprisingly, the hormone sensing cells were producing Lama5, which is critical for the proper function of these cells. Without expression of Lama5 gene, the hormone sensing cells will lose their identity, and can't support growth of the epithelium for instance during pregnancy", says Doctor Johanna Englund, the main author of the study.

The study was conducted using for example organoid culture of isolated epithelial cells from mouse mammary glands. The organoids can in specific conditions be induced to produce milk.

"Our results suggest that lack of ECM factor Lama5 impairs also milk production", Englund says.

Results from this study can help to understand how breast cancer is initiated. 70-80% of breast cancers arise from the hormone sensing cells, and it is conceivable that these cancer cells are also dependent on Lama5 for their growth.

Credit: 
University of Helsinki

Feedback activity in the visual cortex is necessary for the perception of objects

video: How neurons in the primary visual cortex of the mouse contribute to perception and detect behaviorally relevant figures on irrelevant backgrounds.

Image: 
Lisa Kirchberger, Matthew Self, Pieter Roelfsema - Netherlands Institute for Neuroscience

An important function of our vision is to segregate relevant figures from the irrelevant background. When we look at a visual stimulus, it drives a cascade of neural activity from low-level to higher level visual brain areas. The higher areas also provide feedback to the lower areas, where figures elicit more activity than the background, as if figures in the brain are highlighted with extra activity. Researchers from the Netherlands Institute of Neuroscience (NIN) now showed that feedback causes the extra neuronal activity in low-level areas and that the extra activity is essential for figure-ground perception. The findings were published in Science Advances on the 30th June.

Silencing the brain with light to change perception

The primary visual cortex, also known as V1, is the first cortical brain area that receives visual information from the eyes and sends the information on to 'higher' brain areas for further processing. The research team, led by Pieter Roelfsema and Matthew Self, used optogenetics, a technique using light to silence nerve cells, in V1 in mice who had been trained to detect visual stimuli.

Disrupting the conversation between brain areas renders objects invisible

Critically, the researchers silenced only the late part of V1's response, allowing V1 to pass the visual information on to higher areas but preventing the feedback from higher areas back to V1. The result was dramatic and surprising: "When we allowed V1 to activate the higher areas, but curtailed feedback, mice only detected simple stimuli, but not stimuli on a complex background. This shows that feedback to V1 is necessary for figure-ground segregation" explained Lisa Kirchberger, the lead researcher on the project.

The researchers then silenced activity in the higher visual areas and found that it reduced the enhanced activity elicited by figures. "The results show that higher visual areas send information about objects back to V1 in the form of feedback. V1 and the higher areas are engaged in a conversation and if we disrupt the conversation by silencing V1 we can render objects invisible".

The paper represents a major step forward in our understanding of the role that feedback and sustained neural activity play in allowing us to see the world. Mice have very comparable visual systems to humans and it is likely that these results will help us to understand what happens when the visual system makes mistakes, such as in the hallucinations and visual distortions present in diseases such as schizophrenia.

Credit: 
Netherlands Institute for Neuroscience - KNAW

New beetle found in fossil feces attributed to dinosaur ancestor

image: The tiny beetle Triamyxa coprolithica is the first-ever insect to be described from fossil feces.

Image: 
Qvarnström et al.

The tiny beetle Triamyxa coprolithica is the first-ever insect to be described from fossil faeces. The animal the researchers have to thank for the excellent preservation was probably the dinosaur ancestor Silesaurus opolensis, which 230 million years ago ingested the small beetle in large numbers.

In a recently published study in Current Biology, vertebrate palaeontologists from Uppsala University and entomologists from National Sun Yat-sen University (Taiwan), Friedrich-Schiller-Universität Jena (Germany), and Universidad de Guadalajara (Mexico) used synchrotron microtomography to 3D-reconstruct the beetles while they were still trapped within the fossilised faecal matter. The coprolite contained abundant beetle body parts, most belonging to the same small species. A few specimens were found nearly complete, with much of the delicate legs and antennae still intact. The well-preserved state of these fossils made it possible to produce a detailed description of the new beetle genus and to compare it with more modern ones. Triamyxa coprolithica represents a previously unknown extinct lineage of the suborder Myxophaga, whose modern representatives are small and live on algae in wet environments.

"We were absolutely amazed by the abundance and fantastic preservation of the beetles in the coprolite fragment. In a way, we must really thank Silesaurus, which likely was the animal that helped us accumulating them," says Martin Qvarnström, researcher at Uppsala University and one of the co-authors of the paper.

Silesaurus opolensis - the probable producer of the coprolite - was a relatively small dinosaur ancestor with an estimated body weight of 15 kilograms that lived in Poland approximately 230 million years ago. In a previous study, the authors assigned coprolites with disarticulated beetle remains to Silesaurus based on the size and shape of the coprolites as well as several anatomical adaptations in the animal. Silesaurus possessed a beak at the tip of its jaws that could have been used to root in the litter and perhaps peck insects off the ground, somewhat like modern birds. But although Silesaurus ingested numerous individuals of Triamyxa coprolithica, the beetle was likely too small to have been the only targeted prey. Instead, Triamyxa likely shared a habitat with larger beetles, which are represented by disarticulated remains in the coprolites, and other prey, which never ended up in the coprolites in a recognisable shape.

"I never thought that we would be able to find out what the Triassic precursor of the dinosaurs ate for dinner," says Grzegorz Nied?wiedzki, palaeontologist at Uppsala University and one of the co-authors of the paper.

The preservation of the beetles in the coprolite is similar to specimens from amber, which normally yield the best-preserved insect fossils. Amber, however, was mainly formed during relatively recent geological time. This study shows that coprolites may be valuable for studying early insect evolution and, at the same time, the diet of extinct vertebrates.

The synchrotron scanning was carried out at the European Synchrotron Radiation Facility (ESRF) in Grenoble.

Credit: 
Uppsala University

Does socioeconomic status explain why Black people with MS have more disability?

MINNEAPOLIS - A new study suggests that even when differences in socioeconomic status are taken into consideration, Black people with multiple sclerosis (MS) may be more negatively impacted by the disease than white people with MS. The research is published in the June 30, 2021, online issue of Neurology®, the medical journal of the American Academy of Neurology. The study found that Black people with MS had lower scores on certain measures of neurological health, like dexterity and walking tests and showed more evidence of disease progression on brain scans.

"While lower socioeconomic status appears to be linked to doing worse on tests of neurologic performance in white people with MS, we do not see that for Black people with MS, at least at the single time point we examined," said study author Lana Zhovtis Ryerson, MD, of NYU Langone Health in New York City, and a member of the American Academy of Neurology.

The study looked at 1,214 people who identified as Black and 7,530 people who identified as white. Researchers also took a more detailed look at socioeconomic status based on neighborhood for 288 of the Black people in the study and 1,046 of the white people.

Researchers also looked at common neurological tests for people with MS. In a 50-question cognitive processing test, the Black people with MS, on average, scored five points lower than white people with MS. For physical tests like the 25-foot walking test, Black people with MS were an average of 0.66 seconds slower. In a manual dexterity test, Black people with MS were an average of 2.11 seconds slower.

When looking at brain lesions, which can indicate disease progression, researchers found that Black people had, on average, larger lesion volumes on their brain scans compared to white people.

Researchers then looked at the smaller group of people, using a more detailed measure of socioeconomic status. For white people with MS, lower household income was associated with slower cognitive processing and walking speeds, while a worse score on the socioeconomic test was associated with slower cognitive processing and manual dexterity speeds. For Black people in the study, lower income was only associated with less manual dexterity. Having worse socioeconomic scores was not associated with differences in cognitive processing, walking or manual dexterity speeds.

"Future studies should consider the role of unmeasured factors like systemic racism to see if they may play a role in greater disability among Black people with MS," Zhovtis Ryerson said. "These results also reinforce the need for more diverse clinical trials and research focusing on treatment strategies specifically for Black people to identify whether certain therapies or more aggressive early treatment could help slow down disability over time."

A limitation of the study is that it was based on one point in time and may not reflect associations over time.

Credit: 
American Academy of Neurology

Eating disorder behaviors alter reward response in the brain

Researchers have found that eating disorder behaviors, such as binge-eating, alter the brain's reward response process and food intake control circuitry, which can reinforce these behaviors. Understanding how eating disorder behaviors and neurobiology interact can shed light on why these disorders often become chronic and could aid in the future development of treatments. The study, published in JAMA Psychiatry, was supported by the National Institutes of Health.

"This work is significant because it links biological and behavioral factors that interact to adversely impact eating behaviors," said Janani Prabhakar, Ph.D., of the Division of Translational Research at the National Institute of Mental Health, part of NIH. "It deepens our knowledge about the underlying biological causes of behavioral symptom presentation related to eating disorders and will give researchers and clinicians better information about how, when, and with whom to intervene."

Eating disorders are serious mental illnesses that can lead to severe complications, including death. Common eating disorders include anorexia nervosa, bulimia nervosa, and binge-eating disorder. Behaviors associated with eating disorders can vary in type and severity and include actions such as binge-eating, purging, and restricting food intake.

In this study, Guido Frank, M.D., at the University of California San Diego, and colleagues wanted to see how behaviors across the eating disorder spectrum affect reward response in the brain, how changes in reward response alter food intake control circuitry, and if these changes reinforce eating disorder behaviors. The study enrolled 197 women with different eating disorders (including anorexia nervosa, bulimia nervosa, binge-eating disorder, and other specified feeding and eating disorders) and different body mass indexes (BMIs) associated with eating disorder behaviors, as well as 120 women without eating disorders.

The researchers used cross-sectional functional brain imaging to study brain responses during a taste reward task. During this task, participants received or were denied an unexpected, salient sweet stimulus (a taste of a sugar solution). The researchers analyzed a brain reward response known as "prediction error," a dopamine-related signaling process that measures the degree of deviation from the expectation, or how surprised a person was receiving the unexpected stimulus. A higher prediction error indicates that the person was more surprised, while a lower prediction error indicates they were less surprised. They also investigated whether this brain response was associated with ventral-striatal-hypothalamic circuitry, a neural system associated with food intake control.

The researchers found that there was no significant correlation between BMI, eating disorder behavior, and brain reward response in the group of women without eating disorders. In the group of women with eating disorders, higher BMI and binge-eating behaviors were associated with lower prediction error response. Further, for the women with eating disorders, the direction of ventral striatal-hypothalamic connectivity was the reverse of those without eating disorders, with connectivity directed from the ventral striatum to the hypothalamus. This connectivity was positively related to the prediction error response and negatively related to feeling out of control after eating.

These results suggest that for the women with eating disorders, eating disorder behaviors and excessive weight loss or weight gain modulated the brain's dopamine-related reward circuit response, altering brain circuitry associated with food intake control, and potentially reinforcing eating disorder behaviors. For example, women with anorexia nervosa, restrictive food intake, and low BMIs had a high prediction error response. This response may strengthen their food intake-control circuitry, leading these women to be able to override hunger cues. In contrast, the opposite seems to be the case for women with binge-eating episodes and higher BMIs.

"The study provides a model for how behavioral traits promote eating problems and changes in BMI, and how eating disorder behaviors, anxiety, mood, and brain neurobiology interact to reinforce the vicious cycle of eating disorders, making recovery very difficult," said Dr. Frank.

Overall, this study suggests that behavioral traits, including food intake behavior, contribute to eating disorder maintenance and progression by modulating one's internal reward response and altering food intake control circuitry. However, further research is needed to investigate treatments that could target and change behaviors for individuals with eating disorders to achieve lasting recovery.

Credit: 
NIH/National Institute of Mental Health

Where are the Foreigners of the First International Age?

image: Aerial view of Alalakh in the Amuq Plain (Turkey).

Image: 
Murat Akar, Tell Atchana Excavations

The Bronze Age in the eastern Mediterranean has long been considered by researchers to have been the 'first international age,' especially the period from 1600-1200 BC, when powerful empires from Anatolia, Mesopotamia, and Egypt set up large networks of subordinate client kingdoms in the Near East. These empires fought, traded, and corresponded with one another, and ancient texts from the period reveal rich economic and social networks that enabled the movement of people and goods.

A new study conducted by an interdisciplinary team of archaeologists, geneticists, and isotope experts, and published in PLOS ONE, investigated the movement of people in this period at a single regional center, a Bronze Age city-state called Alalakh in present-day southeastern Turkey. Their results indicate that the majority buried at Alalakh were raised locally and descended from people who lived in the region.

The team's goal was to see if the high levels of interregional connectivity evidenced by the architecture, texts, and artifacts found at the site during 20 years of excavations, sponsored by the Turkish Ministry of Culture and Tourism and Hatay Mustafa Kemal University, could be detected among the population buried at the city.

To do so, they conducted strontium and oxygen isotope analyses on tooth enamel, which can detect whether an individual grew up locally at Alalakh or moved there only during adulthood. The genetic data on the other hand can be used to determine where a person's recent ancestors came from.

The isotope analysis identified several non-local individuals. However, their DNA showed an ancestry that was local to Alalakh and neighbouring regions. "There are two possible explanations for our findings," said co-lead author Stefanie Eisenmann from the Max Planck Institute for the Science of Human History. "Either these individuals are short-distance migrants from the region or return-migrants, people whose parents or grandparents originally came from Alalakh."

Only one sampled individual, an adult woman, was not part of the local gene pool, instead showing ancestry that most closely matched groups in Central Asia. However, her isotopic signatures suggested a local upbringing. "We expected the isotope analysis to show that this person immigrated to Alalakh, since her genetic data was so different from the rest of the population, so we were surprised to see that she was likely native to Alalakh. It could have been her parents or grandparents who made the move, instead," explained Tara Ingman, the other lead-author of the study from Koç University.

While different types of mobility were identified, including short-distance, long-distance, and return migration, there were no complete foreigners in the dataset. Most people were born and raised at Alalakh and also their ancestors came from the region.

"There are several ways to explain this. It is possible that far less long-distance migrants were living at Alalakh than we had previously thought. Another possibility is that we haven't found their graves, yet. Perhaps most individuals that came from far away were not buried directly at Alalakh, or in a way we cannot trace," said Murat Akar, director of the excavations.

Credit: 
Max Planck Institute of Geoanthropology