Culture

In Europe, Italians are the richest population in terms of genetic wealth. This is now common knowledge. The gradient of their genetic variability, scattered all over the peninsula, encloses on a small scale the whole genetic variance between southern and continental Europeans. This amazing diversity started to accumulate soon after the Late Glacial Maximum, which ended approximately 19,000 years ago.

This is what some researchers of the University of Bologna report in a paper published in the BMC Biology journal. It is the first time that a group of scientists is able to go so back in time in retracing Italians' genetic history. Results also show that there are some genetic peculiarities characterising people living in the north and south of Italy, that evolved in response to different environments. These peculiarities contribute to reducing, on the one hand, the risk of kidney inflammation and skin cancers, and, on the other hand, the risk of diabetes and obesity, favouring sometimes a longer lifespan.

"Gaining an understanding of the evolutionary history of the ancestors of Italians allows us to better grasp the demographic processes and those of environmental interactions that shaped the complex mosaic of ancestry components of today's European populations", explains Marco Sazzini, one of the principal investigators of this study and professor of Molecular Anthropology at the University of Bologna. "This investigation provides valuable information in order to fully appreciate the biological characteristics of the current Italian population. Moreover, it let us understand the deep causes that can impact on this population's health or on its predisposition to a number of diseases".

AN UNEXPECTED OUTCOME

To carry out this study, researchers sequenced the entire genome of forty participants, who were selected as representatives of the biological variability of the Italian population with a good approximation. The analysis brought to the fore more than 17 million genetic variants. Scientists then made a twofold comparison. First, they compared these data against the genetic variants observed in other 35 populations from Europe and from the Mediterranean. Second, they compared the same data against the genetic variants found in studies on almost 600 human remains dating from the Upper Palaeolithic (approx. 40,000 years ago) to the Bronze Age (approx. 4,000 years ago).

These comparisons reached such high levels of precision that it was possible, for the first time, to go way back in time in Italians' genetic history, extending the investigation to very remote time periods with respect to what achieved by previous studies. Eventually, this led to the identification of traces left in Italians' gene pool by events that just followed the last glaciation, which ended more or less 19,000 years ago.

The bulk of the scholarship in this field has so far suggested that the oldest events leaving a trace in Italians' DNA were the migrations that had taken place in the Neolithic and the Bronze Ages, between 7,000 and 4,000 years ago. The results of this study show, on the contrary, that the earliest biological adaptations to the environment and migrations underlying Italians' extraordinary genetic diversity are much older than previously thought.

CLIMATE CHANGES AND POST-GLACIAL MIGRATIONS

Researchers traced the evolutionary history of the two groups at the opposite ends of Italians' gradient of genetic variability. This means that they evaluated and measured differences between the gene pools of participants from southern and northern Italy and observed when these differences became evident.

"We observe some partially overlapping demographic trends among the ancestors of these two groups from 30,000 years ago and for the remaining years of the Upper Palaeolithic", illustrates Stefania Sarno, a researcher at the University of Bologna and one of the co-first authors of the paper. "However, we witness to a significant variation between their gene pools from the Late Glacial period, thus some thousands of years before those great migrations that happened in Italy from the Neolithic onwards".

Here, the main hypothesis is that with temperatures rising and, as a consequence, glaciers shrinking, some groups of people who made it through the glaciation period thanks to "glacial refugia" in central Italy, moved north and drifted away, and thus progressively isolating themselves, from the inhabitants of southern Italy.

The DNA of people living in northern Italy shows traces of these post-glacial migrations. If compared to individuals from southern Italy, Italians from the north present a close genetic relation to human remains attributed to ancient European cultures such as the Magdalenian and the Epigravettian cultures and dated respectively between 19,000 and 14,000 years ago and between 14,000 and 9,000 years ago. Moreover, in northern Italians' gene pool ancestry components even more ancient were observed, such as those proper of Eastearn European hunter-gatherers, which are thought to characterize all European populations between 36,000 and 26,000 years ago and that later on spread again to western Europe with migratory movements from "glacial refugia" during the Late Glacial period.

Conversely, in southern Italians, these post-glacial migrations traces seem to vanish, as more recent events significantly reshaped their gene pool. This is confirmed by their closer genetic relation with Neolithic human remains from Anatolia and the Middle East, and with Bronze-Age remains from the South Caucasus. Differently from the north of Italy, the south was the main hub for migratory movements, which firstly spread agriculture to the Mediterranean area during the Neolithic transition, and then, during Bronze Age, fostered a new ancestry component. The latter differs from the ancestry component associated with populations of the Eurasian steppe that spread during the same time across continental Europe and northern Italy.

GENETIC ADAPTATIONS: DIFFERENCES AND PECULIARITIES ACROSS ITALY

19,000 years ago, after the end of the Last Glacial Maximum, ancestors of northern and southern Italians started living in increasingly different environmental and ecological contexts, which gradually led to the emergence of differences and peculiarities in their gene pools.

For millennia, the populations resettling in northern Italy endured abrupt climate changes and environmental pressures similar to those of the Last Glacial Maximum. These circumstances brought to the evolution of specific biological adaptations. For instance, populations in northern Italy developed a metabolism optimized for a diet rich in calories and animal fat, which are essential to survive in cold climates. "In the subjects from northern Italy, we observed changes in the gene networks regulating insulin and body-heat production as well as in those responsible for fat tissue metabolism", says Paolo Garagnani, professor of Experimental Medicine and Pathophysiology at the University of Bologna. "These changes could have developed, today, in key factors reducing the susceptibility to diseases like diabetes and obesity".

While this was happening in northern Italy, in the south, a warmer climate exposed its populations to a different kind of environmental pressures. The genomes of people from southern Italy show changes in the genes encoding for mucins, which are proteins to be found in the mucous membranes of the respiratory and gastro-intestinal systems and that prevent pathogens to attack the tissues. "These genetic adaptations may have evolved in response to ancient micro-organisms", says Paolo Abondio, Ph.D. student at the University of Bologna and another co-first author of this study. "Some scholars have linked some of these genetic variants with a reduced susceptibility to Berger's disease, which is a common inflammation affecting the kidneys and is indeed less frequent in the south than in the north of Italy".

Researchers identified also other peculiarities in the genome of southern Italians. For example, there are some modifications in the genes regulating the production of melanin, the pigment that provides colour to the skin. Most probably, these alterations developed in response to more intense sun-light and to a higher number of sunny days that characterise the Mediterranean regions. In turn, these alterations may also have contributed to a lower incidence of skin cancers among southern Italians. "We observed that some of these genetic variants have been also linked to a longer lifespan. This is also true for other genetic modifications which are characteristic of southern Italians. These are found on genes involved in the arachidonic acid metabolism and on those encoding for FoxO transcription factors", according to Claudio Franceschi, Emeritus Professor of the University of Bologna.

THE AUTHORS OF THE STUDY

The study was led by professors of the University of Bologna, Marco Sazzini, Claudio Franceschi and Paolo Garagnani, in collaboration with Patrick Descombes (Nestlé Research Center, Lausanne, Switzerland) and Massimo Delledonne (University of Verona). A paper entitled "Genomic history of the Italian population recapitulates key evolutionary dynamics of both Continental and Southern Europeans" was then published in the BMC Biology journal.

The study featured researchers of the Molecular Anthropology Lab and the Centre for Genome Biology of the Department of Biological, Geological and Environmental Sciences at the University of Bologna: Marco Sazzini, Paolo Abondio, Stefania Sarno, co-first authors of the paper, and also Sara De Fanti, Claudia Ojeda-Granados, Cristina Giuliani, Alessio Boattini and Davide Pettener. Moreover, researchers at the Department of Experimental, Diagnostic and Specialty Medicine also took part in the study: Chiara Pirazzini, Elena Marasco, Gastone Castellani, Claudio Franceschi and Paolo Garagnani. Researchers of these two departments worked together within the framework of the activities of the Interdepartmental Center "Alma Mater Research Institute on Global Challenges and Climate Change".

Donata Luiselli from the Department of Cultural Heritage of the University of Bologna also participated in this study. Finally, Guido Alberto Gnecchi Ruscone (Max Planck Institute for the Science of Human History in Jena, Germany), Massimo Delledonne (University of Verona), Luciano Xumerle (University of Verona), Alberto Ferrarini (University of Verona) and researchers of the Nestlé Research Center in Lausanne (Switzerland), of the Policlinico of Milan, of the University of Florence and of the University of Calabria took part in the study.

New York, NY (May 21, 2020)--Mount Sinai scientists have identified biological markers present in childhood that relate to the degenerative and often fatal neurological disease called amyotrophic lateral sclerosis, also known as ALS or Lou Gehrig's disease, according to a study published in the Annals of Clinical and Translational Neurology in May. (https://www.youtube.com/watch?v=Bw-_XUZssMM&feature=youtu.be)

The researchers found the markers in the teeth of patients who went on to develop ALS as adults. They used lasers to map growth rings that form daily in the teeth and discovered evidence in the growth rings formed at birth and within the first 10 years of life that patients with ALS metabolized metals differently than patients without the disease.

ALS is a condition that usually manifests when someone is in their 50s or 60s. The cause is not known, and there is no test to predict its onset. Genetic studies have not revealed a great deal yet, and while experts believe environmental factors play a significant role in the development of the disease, there have been no clear indications of which ones.

"This is the first study to show a clear signature at birth and within the first decade of life, well before any clinical signs or symptoms of the disease," said senior author Manish Arora, BDS, MPH, PhD, Edith J. Baerwald Professor and Vice Chair of Environmental Medicine and Public Health at the Icahn School of Medicine at Mount Sinai. "We hope in the long term, after validation of this work in larger studies, that this will lead to preventive strategies. What's exciting about this work is that we are looking at biological pathways that we could potentially modify with drug development."

The study showed dysregulated uptake of a mixture of essential elements, including zinc and copper, as well as toxins like lead and tin, in 36 ALS patients compared to 31 controls. The markers of metal uptake dysregulation were also observed in teeth from an ALS mouse model that also showed differences in the distribution of metals in the brain compared to controls.

"Our previous work showed that the dysregulation of elemental metabolism in early life was associated with the onset of neurological disease such as autism and ADHD," said Christine Austin, PhD, Assistant Professor of Environmental Medicine and Public Health at the Icahn School of Medicine at Mount Sinai, a major contributor to this work. "This study shows that metabolic dysregulation is also associated with neurological conditions with a much greater lag to symptom onset".

Researchers at the University of Michigan played an important role in this study, and their clinics provided samples and data from ALS patients and patients in the control group.

(Vienna, Friday, 22 May, 2020) Those who are socially isolated are over 40% more likely to have a cardiovascular event, such as a heart attack or stroke, than those who were socially integrated, new research has shown.

The German study, due to presented tomorrow at the European Academy of Neurology (EAN) Virtual Congress, found that those who are socially isolated are almost 50% more likely to die from any cause. The research also showed that a lack of financial support independently increased the risk of cardiovascular events.

Performed within the Heinz Nixdorf Recall study (HNR) and led by Dr Janine Gronewold and Prof Dirk M. Hermann from the University Hospital in Essen, Germany, the research analysed data from 4,316 individuals (average age 59.1 years) who were recruited into the large community-based study between 2000 and 2003.

The study participants entered the study with no known cardiovascular disease and they were followed for an average of 13 years. At the start of the study, information was collected on different types of social support, with social integration assessed based on marital status and cohabitation, contact with close friends and family, and membership of political, religious, community, sports or professional organisations.

"We have known for some time that feeling lonely or lacking contact with close friends and family can have an impact on your physical health", commented Dr Gronewold. "What this study tells us is that having strong social relationships is of high importance for your heart health and similar to the role of classical protective factors such as having a healthy blood pressure, acceptable cholesterol levels, and a normal weight."

Professor Jöckel, one of the PI's of the HNR added, "This observation is of particular interest in the present discussion on the COVID-19 pandemia, where social contacts are or have been relevantly restricted in most societies."

During the 13.4 years of follow-up, 339 cardiovascular events such as heart attacks or strokes occurred, and there were 530 deaths among the study participants. After adjusting for (removing the influence of) other factors that might have contributed to these events and deaths (for example, standard cardiovascular risk factors), a lack of social integration was found to increase the future risk of cardiovascular events by 44% and to increase the risk of death from all causes by 47%, A lack of financial support was associated with a 30% increased risk of cardiovascular events.

"We don't understand yet why people who are socially isolated have such poor health outcomes, but this is obviously a worrying finding, particularly during these times of prolonged social distancing," said Dr Gronewold. "What we do know is that we need to take this seriously, work out how social relationships affect our health, and find effective ways of tackling the problems associated with social isolation to improve our overall health and longevity," said Prof Hermann.

Facing a scarcity of pollen, bumblebees will nibble on the leaves of flowerless plants, causing intentional damage in such a way that accelerates the production of flowers, according to a new study, which reports on a previously unknown behavior of bumblebees. The leaf-damaging bumblebee bites have a drastic effect on plant flowering, compelling some to bloom two weeks to a full month earlier. Although the mechanisms by which deliberate bee damage accelerate flowering remain unclear, the results reveal bumblebees as powerful agents in influencing the local availability of floral resources. "An encouraging interpretation of the new findings is that behavioral adaptations of flower-visitors can provide pollination systems with more plasticity and resilience to cope with climate change than hitherto suspected," writes Lars Chittka in a related Perspective. Plants and pollinators rely on one another for survival. Just as pollinators, like bumblebees, depend on flowers for crucial nutrition, plants need pollinators to reproduce. This symbiotic relationship is kept in balance by the synchronous timing of the emergence of hibernating insects and spring blossoms as spring temperatures rise and the days get longer. But this fragile arrangement is threatened by climate change. For instance, warming early season temperatures could cause pollinators to wake up too soon, before the springtime bloom and without a source of food. Foteini Pashalidou and colleagues discovered an adaptive strategy used by food-deprived bumblebees to manipulate the timing of a plant's flowering. Pashalidou et al. observed bumblebee workers from pollen-starved colonies use their mouthparts to cut distinctively shaped holes in the leaves of flowering plants, which resulted in them flowering significantly earlier. The authors were not able to reproduce the flower-stimulating effects by mimicking the damage on their own, however, suggesting a yet-unknown feature distinct to the bees' approach. "Understanding the molecular pathways by which one could accelerate flowering by a full month, as reported [by Pashalidou et al.], would be a horticulturalist's dream," Chittka writes.

In lieu of a vaccine or reliable preventative medications, the only approaches currently available to help prevent the spread of COVID-19 are behavioral - handwashing, mask-wearing and social distancing, for example. In a Policy Forum, Johannes Haushofer and Jessica Metcalf argue that it is crucial to identify the "nonpharmaceutical interventions" (NPIs) that most effectively reduce virus transmission at the lowest economic and psychological costs. While handwashing initiatives are relatively inexpensive, sanctioned school and business closures are extremely costly. However, many NPIs are often applied without rigorous evaluation and the approaches to implementing and regulating them are varied, thus making their impact relative to their cost difficult to know. Haushofer and Metcalf discuss how randomized controlled trials (RCTs), compartmental models and spillovers can each be harnessed to evaluate and identify the interventions that work best during a pandemic situation. The authors demonstrate how RCTs can be practically and ethically conducted during a pandemic and used to systematically evaluate the impact of specific intervention strategies, as well as how the effects of NPIs on disease transmission can be estimated using epidemiological compartmental models. What's more, Haushofer and Metcalf suggest that "spillover" effects - or the spread of intervention strategies into non-targeted groups - can be leveraged to increase the overall impact and coverage of NPIs. "If policymakers and scientists combine insights from infection disease epidemiology with carefully and ethically designed impact evaluation, alongside other... methods for studying impact, they will have a powerful tool for reducing the human health, societal and economic costs in the SARS-CoV-2 pandemic," write the authors.

Tropical forests face an uncertain future under climate change, but new research published in Science suggests they can continue to store large amounts of carbon in a warmer world, if countries limit greenhouse gas emissions.

The world's tropical forests store a quarter-century worth of fossil fuel emissions in their trees alone. There are fears that global heating can reduce this store if tree growth reduces or tree death increases, accelerating climate change.

An international research team measured over half a million trees in 813 forests across the tropics to assess how much carbon is stored by forests growing under different climatic conditions today.

The team reveal that tropical forests continue to store high levels of carbon under high temperatures, showing that in the long run these forests can handle heat up to an estimated threshold of 32 degrees Celsius in daytime temperature.

Yet this positive finding is only possible if forests have time to adapt, they remain intact, and if global heating is strictly limited to avoid pushing global temperatures into conditions beyond the critical threshold.

Lead author Dr Martin Sullivan, from the University of Leeds and Manchester Metropolitan University, said: "Our analysis reveals that up to a certain point of heating tropical forests are surprisingly resistant to small temperature differences. If we limit climate change they can continue to store a large amount of carbon in a warmer world.

"The 32 degree threshold highlights the critical importance of urgently cutting our emissions to avoid pushing too many forests beyond the safety zone.

"For example, if we limit global average temperatures to a 2°C increase above pre-industrial levels this pushes nearly three-quarters of tropical forests above the heat threshold we identified. Any further increases in temperature will lead to rapid losses of forest carbon."

Forests release carbon dioxide into the atmosphere when the amount of carbon gained by tree growth is less than that lost through tree mortality and decay.

The study is the first to analyse long-term climate sensitivity based on direct observation of whole forests across the topics. The research suggests that over the long-term, temperature has the greatest effect on forest carbon stocks by reducing growth, with drought killing trees the second key factor.

The researchers conclude that tropical forests have long-term capacity to adapt to some climate change, in part because of their high biodiversity as tree species better able to tolerate new climatic conditions grow well and replace less well-adapted species over the long-term.

But maximizing this potential climate resilience depends on keeping forests intact.

Co-author Professor Beatriz Marimon from the State University of Mato Grosso in Brazil studies some of the world's hottest tropical forests in central Brazil. She noted: "Our results suggest that intact forests are able to withstand some climate change. Yet these heat-tolerant trees also face immediate threats from fire and fragmentation.

"Achieving climate adaptation means first of all protecting and connecting the forests that remain."

Professor Marimon notes the clear limits to adaptation. "The study indicates a heat threshold of 32 degrees Celsius in daytime temperature. Above this point tropical forest carbon declines more quickly with higher temperatures, regardless of which species are present.

"Each degree increase above this 32 degree threshold releases four-times as much carbon dioxide as would have been released below the threshold."

The insights into how the world's tropical forests respond to climate were only possible with decades of careful fieldwork, often in remote locations. The global team of 225 researchers combined forests observations across South America (RAINFOR), Africa (AfriTRON) and Asia (T-FORCES). In each monitoring plot the diameter of each tree and its height was used to calculate how much carbon they stored. Plots were revisited every few years to see how much carbon was being taken in, and how long it was stored before trees died.

To calculate changes in carbon storage required identifying nearly 10,000 tree species and over two million measurements of tree diameter, across 24 tropical countries. According to Professor Simon Lewis of the University of Leeds and University College London: "The amount of carbon absorbed and stored by forests is a crucial element in how the Earth responds to climate change."

"The study underlines why long-term research collaboration is essential for understanding the effects of environmental change. Scientists need to work together more than ever, as monitoring the health of our planet's great tropical forests is vital for all of us."

Cutting carbon emissions enough to keep forests within the safety zone will be very challenging. Study author Professor Oliver Phillips of the University of Leeds said: "Keeping our planet and ourselves healthy has never been more important. Right now, humanity has a unique opportunity to make the transition toward a stable climate.

"By not simply returning to 'business as usual' after the current crisis we can ensure tropical forests remain huge stores of carbon. Protecting them from climate change, deforestation and wildlife exploitation needs to be front and centre of our global push for biosecurity.

"Imagine if we take this chance to reset how we treat our Earth. We can keep our home cool enough to protect these magnificent forests - and keep all of us safer."

COLUMBUS, Ohio - Ohio has seen a growing disparity between abortion rates in rural and urban communities, later abortions, and less use of medication abortion care as the state has heavily regulated abortion and clinics have closed, a new study has found.

Researchers say their study raises concerns about inadequate and inconsistent access to a full spectrum of reproductive health care.

The researchers looked at abortion services performed in Ohio from 2010 to 2018, a time when more than 15 new abortion regulations were instituted and when the number of surgical abortion clinics in the state dropped from 15 to eight. The study, led by Alison Norris of The Ohio State University, appears today (May 21, 2020) in the American Journal of Public Health.

In this study, researchers examined a variety of characteristics of those who received abortions during the eight-year study period, including how far along they were in their pregnancies, county of residence and what methods of abortion were used.

Nationally and in Ohio, abortion rates declined significantly during this time period. But a decrease in early first-trimester abortions and simultaneous increase in later first-trimester abortions was unique to Ohio, and may signal delays in women and teens receiving prompt care because of the burdens they have to overcome to get that care, said Norris, an associate professor of epidemiology in Ohio State's College of Public Health.

"Abortion care is one of the safest procedures that we have. Because it becomes more complex later in pregnancy, women benefit from quick access to abortion services when they choose to end a pregnancy," Norris said.

The research is part of a multidisciplinary reproductive health research consortium called the Ohio Policy Evaluation Network, or OPEN, which includes scientists from Ohio State, the University of Cincinnati, Cincinnati Children's Hospital and Case Western Reserve University.

Ohio's abortion laws include mandatory in-person counseling 24 hours before the procedure and limitations about how abortion can be funded, which can create significant obstacles to early care for some women, Norris said.

From 2010 to 2018, abortion ratios decreased sharply, and disproportionately, in most rural Ohio counties, the study found. In rural counties, the number of abortions per 1,000 live births dropped more than 32 percent compared to the 24 percent reduction seen in urban counties.

And in areas where clinics closed, use of abortion dropped off among women and teens living both within the county and in surrounding counties.

"This geographic inequity in abortion access is concerning, because it likely means that some people who have unintended pregnancies and want to end those pregnancies are not getting the care they want and deserve," Norris said, adding that regulations passed in Ohio during the study period, including requirements that clinics have a written patient transfer agreement with a private hospital, have created administrative hurdles for abortion providers.

Norris said there's no evidence that she's aware of to support the idea that abortions are happening less frequently in rural Ohio because there are fewer unintended pregnancies or less demand for services. In fact, she said, it's possible that unintended pregnancies are more common in some rural areas where access to contraceptive options could also be limited.

"It could actually be the case that there are higher rates of unintended pregnancy in some rural areas, because people who live in those areas have reduced access to all kinds of health care, including high-quality reproductive care," said Norris, adding that the OPEN research team hopes to explore that possibility in future work.

Medication abortion care also decreased significantly in Ohio during this time, likely largely due to the state's narrow interpretation of how the medications had to be dispensed, Norris said.

Nationally, annual abortion rates overall dropped from about 12 per 1,000 women of childbearing age to fewer than 10 per 1,000 during the study period.

"This national trend, one that has also been seen in Ohio, aligns with increased access to contraception and highly effective modes of contraception, particularly long-acting reversible contraceptives," Norris said.

"But declines in the use of abortion are being experienced differently by different groups of people, and that's what we found is happening in Ohio."

While this study focuses on Ohio, it likely has broader implications, Norris said.

"I think we can expect similar experiences for people who live in states with a high regulatory burden around abortion care. It's reasonable to imagine that the things that we see in Ohio are playing out in other places."

Regions of Italy with higher family fragmentation and a high number of residential nursing homes experienced the highest rate of COVID-19 infections in people over age 80, according to a new study published May 21, 2020 in the open-access journal PLOS ONE by Giuseppe Liotta of the University of Rome, Italy, and colleagues.

Italy has been one of the countries most affected by the COVID-19 pandemic. Researchers have speculated that this is due to Italy's age demographics as well as the connectedness of the older and younger generations and high rate of intergenerational contact. If true, this would suggest that regions with larger households would have more severe COVID-19 outbreaks in older adults.

In the new study, researchers used publicly available data published by each Italian administrative region as well as daily situation reports on COVID-19 published by the Italian Ministry of Health and spanning February 28 through March 31, 2020. All household and population data was extracted between April 1 and 7, 2020.

Across Italian regions, the COVID-19 incidence rate ranged from 0.27% to 4.09% of the population being affected. The mean number of household members ranged from 2.02 to 2.58; the percentage of one member households ranged from 28.5 to 40.9; and percentage of COVID-19 cases that occurred in people over age 80 ranged from 4.3 to 23.6. A model that reflected the percent of the population over age 80, days since 50 cases were registered, percentage of nursing home beds in the total population, and mean number of household members was best able to predict the COVID-19 incidence among older people in each region, with an adjusted R-squared value of 0.695 (p

The authors add: "Variables associated with social isolation are risk factors for
increase in the proportion of cases in Italian patients aged >80 years
among the total number of cases." Professor Liotta also notes that "nursing homes bed rate is one of the determinants of SARS-CoV-2 infection rate among the individuals aged>80 in Italy."

New research from the University of East Anglia (UEA) recommends changes to the system which sees drug companies strike deals with competitors to stop them producing cheaper generic alternatives.

These 'pay-for-delay' deals involve a payment from a branded drug manufacturer to a generic maker in order to delay market entry. In return for withdrawing its challenge, the generic firm receives a payment and/or a license authorizing it to enter the market at a later date, but before the expiration of the patent itself.

Such deals may block entry by other generic firms and have been challenged by competition authorities in Europe and the US on grounds of being anticompetitive. They can cost consumers and health systems millions by delaying the introduction of cheaper generic drugs for several years.

Dr Farasat Bokhari, Dr Franco Mariuzzo and Dr Arnold Polanski, of UEA's School of Economics and Centre for Competition Policy, develop a model of generic entry and patent litigation to show that the branded firm can pay off the first generic challenger and then ward off entry by second or later challengers by threatening to launch an authorized generic via the first paid-off challenger. The model captures the essential features of market entry rules for drugs and the patent litigation in both Europe and the US.

Compared to the current first-filer system in the US, where generic exclusivity is awarded to the first generic applicant, the researchers endorse a switch to a system that instead rewards the first successful challenger, which they say will result in fewer pay-for-delay deals.

Publishing their findings today in the Journal of Economics & Management Strategy, they also recommend preventing a branded firm from launching a pseudo or authorized generic against an independent generic that wins patent litigation, as this will prevent pay-for-delay deals for weak patents.

They advise that competition authorities should be cautious about using payment to a generic firm as a workable surrogate to measure the strength of a patent. This is because the payment depends on other factors as well, and therefore low payment does not necessarily mean that the underlying patent is strong and no harm has been caused to the consumers by the pay-for-delay deal.

Dr Bokhari said: "While pay-for-delay deals may be beneficial to some extent, in that they might save courts and administrative bodies, such as patent offices, time and effort, they allow branded drug firms to charge monopoly prices and in a typical deal there may be several years delay in a cheaper version becoming available.

"Investigation and fines can be important in deterring such deals. However, the more important policy question is what can be done to prevent such entry limiting agreements in the first place?

"One also has to ask why such deals are stable in the first place. If a branded firm pays the generic firm to stay out of the market and they accept the deal, what stops the next generic drug maker knocking on the branded firm's door, looking for a similar payoff? And if they do, how much do they have to pay and how can the original deal be profitable?

"The late generic challengers can be credibly threatened that even if they succeed in invalidating the patent and enter, the branded firm will launch the authorized generic prior to their entry and will capture large portion of generic profits. Therefore, it is important that the branded firms' ability to launch authorized generics be legislatively limited."

Previous studies have found that a pay-for-delay deal can cost as much $3.5 billion per year to US consumers - with prices dropping by as much as 75% after generic entry - and can slow a generic entry to the market by up to five years.

University of Melbourne researchers have quantified the toll that having multiple chronic diseases takes in China for the first time, which could have significant implications for its economic and health systems.

Researchers say is also timely as COVID-19 has placed further pressure on the public health emergency management system in China.

Published in The Lancet Global Health, the study is the first national longitudinal data set of its kind. Researchers found multimorbidity* - two or more mental or physical chronic non-communicable diseases (NCDs), such as stroke and cancer - was associated with higher health service use levels and greater financial burden.

It increased with age, female gender, higher per capita household expenditure, and higher educational level. However, it was more common in poorer regions compared with the most affluent regions.

The study used data from the three waves of the China Health and Retirement Longitudinal Study conducted in 2011, 2013 and 2015 with Chinese residents aged 45 years and older. Researchers analysed data from 11,817 respondents.

Overall, 62 per cent of participants had physical multimorbidity in 2015. The study concluded that concerted efforts were needed to reduce health inequalities due to multimorbidity and its adverse economic impact.

The Chinese Government is working towards universal health coverage by 2030, and around 1.2 billion of China's 1.4 billion citizens are already covered by one of three social health insurance programs.

However, low levels of service coverage for some beneficiaries and high levels of patient cost-sharing from out-of-pocket fees for health services have raised concerns about the lack of adequate financial protection for patients with NCDs.

First Author Dr Yang Zhao, a researcher at University of Melbourne's Nossal Institute for Global Health, said China's ongoing social health insurance reforms must reduce out-of-pocket spending for patients with multimorbidity.

"Concerted efforts are needed to reduce health inequalities that arise due to multimorbidity, and its adverse economic impact in population groups," Dr Zhao said. "Social health insurance reforms must place emphasis on reducing out-of-pocket spending for patients with multimorbidity to provide greater financial risk protection."

COVID-19 further complicates the situation. Dr Zhao said a national effort coordinated by the Chinese government has helped to contain its spread.

"Some evidence suggests those with multimorbidity are more susceptible to COVID-19 and more likely to be at risk of severe cases and poor outcomes. However, that situation is temporary," Dr Zhao said. "The Chinese government has made unprecedented efforts and invested enormous resources and these containment efforts have stemmed the spread of the disease."

University of Melbourne Nossal Institute for Global Health senior lecturer and senior author, Dr John Tayu Lee, said chronic conditions were a major contributor to China's health burden, outcome inequalities and economic burden. He said this was likely to increase rapidly with an ageing population and high levels of NCD risk factors.

"Multimorbidity is costly to individuals and health systems," Dr Lee said. "Disease-specific guidelines are inadequate for the effective management of individuals with multimorbidity and new clinical guidelines for multimorbidity are needed in China."

A new review discusses the findings from over 40 studies on coronavirus immunity and what they could mean for the Covid-19 pandemic.

Written by top UK virologists, the article discusses the existing knowledge about immune responses to SARS-CoV-2 and other coronaviruses, and how this could be used to inform virus control strategies. The review, which is free to read in the Journal of General Virology (JGV), collates the available scientific evidence in a number of key areas, including how long immunity to coronaviruses lasts and the prospect of antibody testing.

In the review, Professors Paul Kellam and Wendy Barclay from Imperial College London examine what is so far known about immunity to coronaviruses including SARS, MERS and the four strains of seasonal coronaviruses that circulate in humans every winter. The article goes on to suggest that SARS-CoV-2 could become the fifth seasonal coronavirus with epidemics of the virus occurring over the next several years.

"SARS-CoV-2 is a new virus in humans and because of this we are having to learn quickly many of its basic properties. In the absence of such data right now, we can try to make predictions about the immune response to SARS-CoV-2 by re-examining what we know about the two epidemic coronavirus of humans, SARS and MERS and the four seasonal human coronavirus. We need to be cautious about inferring too much, but it is a good place to start.'

"We do not really know what happens on the pathway of a new coronavirus in humans becoming an endemic seasonal infection, but it could be that when the four seasonal coronavirus first jumped from animals into humans they were much like SARS-CoV-2 in their transmission and pathogenesis. Over time as population immunity to the seasonal coronavirus became widespread, the amount of severe disease probably declines. However, seasonal coronavirus can still cause pneumonia in some people," said Professor Kellam.

A number of factors, including severity of disease influence how long antibody protection against both SARS and MERS lasts. Studies have shown that antibody protection wanes over time. For seasonal coronaviruses where disease is mild, there have even been reports of reinfection after as little as 80 days. "We need to find out many things about SARS-CoV-2 immunity, such as how good is the immune response and how long does it last. We also need to understand if people with mild or asymptomatic infections develop a strong or weak immune response and what measurable properties of immunity predict protection from infection. When we know more about these things, we will be better able to understand how SARS-CoV-2 infections will continue over time. However, vaccines are not infections, therefore it is likely that some of the vaccines candidates will be better at inducing long lasting immunity and protection from infection," said Professor Kellam.

The authors also discuss the currently available antibody tests for SARS-CoV-2 and explain the differences between these tests, their accuracy and limitations. Knowing the level of immunity to SARS-CoV-2 in the population could be key in controlling the spread of disease and understanding how many people are at risk of infection.

"Understanding immune responses to these viruses is on many people's minds- from the public hearing about vaccines, testing and antibodies, to policy makers, and scientists working on or with an interest in the current pandemic." said Alain Kohl, Deputy Editor-in-Chief of JGV). The Editor-in-Chief Paul Duprex added: "This review gives an up to date, and superbly researched overview of this field. Many people will find areas or topics of interest in this article, that should help them understand the important discussions going on. We are delighted to see it published in the journal."

A new study by researchers from the Institute of Evolutionary Biology (IBE), a joint centre of UPF and the Spanish National Research Council (CSIC), shows that, surprisingly, the distribution of mutations in human tumours is more similar to that of chimpanzees and gorillas than that of humans.

The article, which analyses cancer from the evolutionary point of view, is published today, 19 May, in Nature Communications. It was led by Arcadi Navarro and David Juan and involved the researchers Txema Heredia-Genestar and Tomàs Marquès-Bonet.

Mutations are changes that occur in DNA. They are not distributed throughout the genome evenly, but some regions accumulate more and others less. Although mutations are common in healthy human cells, cancer cells display a greater number of genetic changes. During the development of cancer, tumours rapidly accumulate a large number of mutations. In previous studies, however, it had been observed that surprisingly tumours accumulate mutations in very different regions of the genome from those normally observed in humans.

Now, thanks to the data from the project PanCancer, a research team from the IBE has compared the regions of the genome that accumulate more and less mutations in tumour processes, in the recent history of the human population, and in the history of other primates. The results of this new study reveal that the distribution of mutations in tumours is more like that in chimpanzees and gorillas than in humans.

"To date, it was thought that the genetic differences we find when we compare tumours and healthy humans could be caused by the 'abnormal' way tumours have of accumulating mutations. In fact, we know that tumours rapidly accumulate a large number of mutations and that many of their genome repair mechanisms do not work well", comments Txema Heredia-Genestar, first author of the study who recently completed his PhD at the IBE. "But now, we have discovered that many of these genetic differences have to do with our evolutionary history".

The distribution of mutations in humans, skewed by population events

When an individual's genome is sequenced, it is observed to have a small number of new mutations -- some 60-- compared to their parents, those of their parents with respect to their grandparents, and so on with each previous generation. Therefore, in a person, approximately three million mutations can be seen that represent the evolutionary history of the mutations accumulated over hundreds of thousands of years. Of these, a few are recent and most are very old.

However, when tumour mutations are analysed, what is seen are just the mutations that have taken place during the tumour process, since the analysis does not take into account the information on populational history.

"We have seen that the distribution of mutations in the human genome is skewed because of human evolutionary history", Heredia-Genestar details. The manner in which a tumour accumulates mutations is the same as a human cell has of accumulating mutations. "But, we do not see this in the human genome because we have had such a complicated history that has made our distributions of mutations change, and this has deleted the signals we should have", he adds.

Throughout history, the human population has suffered drastic declines and has even repeatedly been on the verge of extinction. This phenomenon is known as a bottleneck, and it causes humans as a species to have very little diversity and fewer mutations: they are very similar to each other. In fact, chimpanzees are four times more genetically diverse than humans.

Therefore, the global way for a cell to accumulate mutations can be observed in chimpanzees because they have not undergone these population events. The study concludes that to understand how mutations accumulate in human cells, which is important for studying tumours, it is more useful to look at how they accumulate in other primates rather than looking at it in human populations , whose signal was destroyed by population events.

"Cancers, like chimpanzees and gorillas, only show the complete mutation landscape of a normal human cell. It is we humans, with our turbulent distant past, who display a distorted distribution of mutations", adds Arcadi Navarro, ICREA research professor at the IBE, full professor at UPF and co-leader of the study.

The research suggests that the conservation and study of the great apes could be highly relevant to understanding human health. David Juan, co-leader of the study, concludes that "in the particular case of the development of tumours, other primates have proved to be a better model for understanding how tumours develop at genetic level than humans themselves. In the future, our closest relatives could shed light on many other human diseases".

Altered gene expression in fat tissue may help explain why individuals who have regained weight after weight loss surgery still experience benefits such as metabolic improvements and a reduced risk of type 2 diabetes. The findings come from a study published in the Journal of Internal Medicine.

The study included women who underwent weight loss surgery, and gene analyses were conducted before and two and five years after surgery. Analyses were also conducted in women who did not undergo surgery.

Most gene expression changes in fat tissue occurred during the first two years after surgery; however, a subset of genes encoding proteins involved in inflammation displayed a continued decrease in expression over five years (during weight regain).

Ecological resources are an important material foundation for the survival, development, and self-realization of human beings. In-depth and comprehensive research and understanding of ecological resources are beneficial for the sustainable development of human society. Advances in observation technology have improved the ability to acquire long-term, cross-scale, massive, heterogeneous, and multi-source data. Ecological resource research is entering a new era driven by big data.

Deep learning is a big data driven machine learning method that can automatically extracting complex high-dimensional nonlinear features. Although deep leanring has achieved better performance for big data mining than traditional statistical learning and machine learning algorithms, there are still huge challenges when processing ecological resource data, including multi-source/multi-meta heterogeneity, spatial-temporal coupling, geographic correlation, high dimensional complexity, and low signal-to-noise ratio. A recent study clarified the aforementioned frontier issues.

The related research paper entitled "The Application of Deep Learning in the Field of Ecological Resources Research: Theory, Methods, and Challenges" has been published in "Science in China: Earth Science" . Prof. GUO Qinghua and Ph.D. student JIN Shichao from Institute of Botany, Chinese Academy of Sciences are co-first authors. GUO Qinghua is the corresponding author. Prof. LIU Yu from Peking University and Prof. XU Qiang from Chengdu University of Technology are co-authored research teams.

Deep learning has made significant progress in many fields with the accumulation of data, the improvement of computing power, and the progress of algorithms. This study focuses on the application of deep learning in the field of ecological resources. The main contents include:

1) An overview of the history, development and basic structure of deep learning (Figure 1). The relationships between ecological resource big data research and deep learning structures represented by convolutional neural networks, recurrent neural networks, and graph neural networks were analyzed (Figure 2)

2) The main tasks of deep learning, common public data sets, and tools in ecological resources were summarized (Figure 2).

3) The application of deep learning in plant image classification, crop phenotype, and vegetation mapping were demonstrated. The application ability and potential of deep learning in structured and unstructured ecological data were analyzed.

4) The challenges and prospects of deep learning in the application of ecological resources were analyzed (Figure 3), including standardization and sharing of data, construction of crowdsourcing collection platform, interpretability of deep neural network, hybrid deep learning with domain knowledge, small sample learning, data fusion, and enrichment and intelligence of applications.

This study explored the relationship between deep learning and ecological resource research. It is of great significance for connecting the technological frontier of computer science with the classical theoretical science in the field of ecological resources. This connection will contribute to the establishment of a new paradigm of theoretical discovery and scientific research in the era of ecological resources big data.

With the aim of making the labour market more flexible, between 1990 and 2010 most of the economies, the European ones in particular, adopted various measures designed to reform their labour markets, which involved making it cheaper to dismiss permanent employees and encouraging the use of temporary contracts. "These reforms were based on the belief that the serious unemployment problems facing these economies were due to the existence of various inflexibilities in the labour market which were hampering a rapid adjustment of these markets when responding to economic shocks," explained Josu Ferreiro, lecturer in the Department of Applied Economics V of the UPV/EHU's Faculty of Economics and Business.

Ferreiro, together with his department colleague Carmen Gómez, and Philip Arestis, a University of Cambridge lecturer, tackled the study of the effect these measures were having on the labour markets of eleven European countries over a 25-year period, from 1988 to 2012. "The cut in dismissal costs was more than half with respect to that stipulated by legislation in the 1980s, both in terms of days worked per year that are paid and in terms of the cut-off figure of monthly salaries that are paid," said the researcher.

Studies had already begun to be published suggesting that these measures had failed to achieve the desired effect and that there was no clear demonstration that more jobs had been created. "We decided to analyse the repercussions that this reduced employment protection was having not only on total employment but also on permanent employment and temporary employment. We studied each of these aspects separately," said Ferreiro.

The results of the analysis were clear, "clearer than what we had expected to find", said the researcher. And the fact is that they found that "the changes introduced to reduce employment protection, in other words, by making it cheaper to dismiss people and by simultaneously promoting temporary contracts, have had no effect on the total employment rate, because what has happened is that temporary employment has increased a lot whereas indefinite employment has fallen hugely. The evolution in employment depends on economic growth alone, and only a higher rate of economic growth generates an increase in employment".

The clearest effect that they in fact found on the job market as a result of the labour reforms was "the restructuring of employment that has taken place. A segmentation has taken place which means we can talk about two categories of workers: those who are on fixed or permanent contracts, and those on temporary contracts. They almost operate as if they were different job markets where the possibility of people on temporary contracts securing an indefinite contract is very remote. What is more, the conditions of work of temporary contracts are more precarious, firstly because the contracts are shorter and secondly because they pay less," he said.

Overreaction of layoffs during the Covid-19 crisis

Ferreiro is in no doubt that companies have been the major beneficiaries of the reforms: "They find a workforce that is much more manageable, more flexible and also cheaper." So much so that right now the rate of temporary employment has reached unprecedented levels that this economist regards as "excessive". He recalls that when the economy began to revive after the economic crisis, "there was an upturn in employment once again, but the employment created was of a temporary nature," he said.

However, the high rate of temporary work means that the employment that is created is highly volatile: a lot of jobs are destroyed the moment economic activity slows down or falls. "And that is what is happening in the crisis we are going through right now: the effect on employment may be much greater than the actual effect on economic activity due to the great flexibility of the labour market. Just as the health system is not equipped to address a huge increase in the number of patients all at once, neither are our economic systems equipped to absorb the fact that all of a sudden, within a four-month period, 20-30% of people lose their jobs," he reflected.

Ferreiro regards this situation as an opportunity for States to change legislation on employment protection: "Within the short to medium term, countries will probably start to rethink this problem of employment legislation more seriously and to consider the fact that these measures implemented in the past have not had the desired effects and that we have to go for models in which an attempt is made to stabilise employment much more."