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Decision-making, a contagious process

Risk, safety - wooden signpost

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Individuals learn to assess the level of prudence, patience or laziness shown by others from observing their behaviour, but most importantly, this influences their own decisions, without their even noticing it. A discovery that could have implications for neuroscience. Do our neighbours’ decisions affect our own? Such is what we are led to believe by the work of Jean Daunizeau and Marie Devaine, two Inserm researchers at the Brain and Spine Institute (ICM) in Paris (Inserm/ CNRS/ UPMC). They studied the behaviour of people making choices requiring prudence, patience or effort, and showed that when these people observe the behaviour of other individuals, they then start imitating them, without even knowing it !

 Underlying this work is a question fundamental to understanding how we make decisions in everyday life: is it a matter of personality, embedded in our DNA, or a process acquired through our education and social interactions? To find out, the researchers studied three characteristics that guide most of our decisions: prudence, patience and effort (or, depending on one’s point of view: risk-taking, impatience and laziness). To do this, they combined mathematics with cognitive psychology. “Social psychology is often criticised for being an over-empirical science, with results that are difficult to reproduce. To circumvent this problem, we use mathematical modelling,” explains Jean Daunizeau, who supervised this work.

In practice, the researchers recruited volunteers and subjected them to decision-making tests. A computer offered them choices requiring various degrees of patience, effort and prudence. For example, they had to choose between winning €2 immediately or €10 a few days later, pressing a soft handle for a small reward or a very hard one for a higher sum, or opting for a lottery that offered a strong chance of winning a small amount or a smaller chance of a big win. The volunteers responded to a series of forty choices of this type, thus allowing the authors to create an algorithm representative of their personality.

 In a second phase, the volunteers had to predict the choices of a fictional character invented using the algorithm, and more (or less) prudent, lazy or patient than the subject himself/herself. When left to their own devices, all the volunteers imagined that this character would make the same choices as themselves, regardless of how they behaved. However, after several errors and a period of adaptation, they ultimately made increasingly better predictions of the algorithm’s responses. Everything happens as though people presume that others think and act like themselves; this is what is known as the false consensus bias. “This phenomenon has already been described in other contexts,” explains Jean Daunizeau, “for aesthetic or moral choices, for example. It stipulates that people believe that their own judgement is shared by most other people. We find that here for choices requiring patience, effort or prudence.” But this bias is progressively offset by learning: having observed the behaviour of the fictional character, the volunteers correctly predict 85% of its choices. “On average, people are therefore able to closely interpret other people’s attitudes,” explain the researchers.

 Finally, the authors subjected the volunteers to a third series of tests, and found that the volunteers’ choices had become more similar to those of the fictional character. “This type of mimicry is relatively unconscious: when they are asked the question, the volunteers are unaware that the nature of their choices has changed, and that they are showing more patience or prudence. This phenomenon is known as the social influence bias, and means that our attitude tends to align with that of others. It was known in relation to certain behaviours, but here we reveal it in decision-making.”

 An improved understanding of how peoples’ decision-making is influenced by the way other people make decisions could have medical implications. Strong mimicry is observed in healthy subjects. What about individuals with psychiatric illnesses that affect social relationships, such as autism or schizophrenia? Here is what the researchers want to confirm: “If there are differences at that level; absence of mimicry could perhaps become a diagnostic element. There would then be a clinical aspect,” concludes the team.

Sunday 2 April: World Autism Awareness Day

Autism

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On 2 April, World Autism Awareness Day takes place with the aim of raising awareness and better informing the general public on the realities of this development disorder. 

Autism is a pervasive developmental disorder that appears during childhood and continues into adulthood. It presents as an altered ability to establish social interactions and communicate, and as behavioural problems.

France has about 100 young people under 20 who have Pervasive Developmental Disorder (PDD). Childhood autism affects about 30,000 of them

Coordinator of the “Autism Research Network”, Catherine Barthélémy, paediatric psychiatrist, emeritus professor of the Tours Faculty of Medicine and former director of the “Autism” team at Inserm Unit 930 (Imaging and Brain), received the 2016 Inserm Honorary Prize for her work.

(…) Along with my team, I helped to prove that autism is a disorder linked to a very early anomaly in neurodevelopment of the brain. A particular setting of brain decoders of social information alters the baby’s ability to relate to other humans. This has nothing to do with any maternal malfunction“, she explains.

Find the autism information file, developed in collaboration with Professor Catherine Barthélémy.

See the video about Catherine Barthélémy.

François DABIS appointed Director of ANRS

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©Paul Avilach

Prof. François Dabis has just been appointed Director of ANRS, an autonomous agency of Inserm, by the Ministers responsible for Research and Health, on the proposal of the Chairman and CEO of Inserm. A physician, academic and internationally renowned researcher, Prof. Dabis specialises in epidemiology and public health. He succeeds Prof. Jean-François Delfraissy, the new President of the National Consultative Ethics Committee.

Prof. François Dabis has just been appointed Director of the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) by the Ministers responsible for Research and Health, on the proposal of the Chairman and CEO of Inserm. Prof. Dabis is 59 years of age. He obtained his Doctorate in Medicine at the University of Bordeaux II in 1983. During his scientific training, Prof. Dabis chose to specialise in epidemiology and public health, first in France, and then at the Harvard School of Public Health in Boston. He spent two years at the US Centers for Disease Control (CDC), in Atlanta, as an Officer of the Epidemic Intelligence Service, from 1984-1986. He obtained his Doctorate in Epidemiology in 1992, at the University of Bordeaux II. From 2001 to 2015, he led the “HIV, Cancer and Global Health” research team at Inserm Centre U 897, at the Institute of Public Health (ISPED) of the University of Bordeaux. He is currently a member of the team “Infectious Diseases in Resource-Limited Countries” of University of Bordeaux/Inserm Research Centre U1219, “Bordeaux Population Health.”

Prof. Dabis is an expert on HIV, internationally recognised for his extensive work on the epidemiology and public health challenges associated with this viral infection. Throughout his teaching and research career, he has focused on evaluating strategies for both prevention of HIV transmission and patient care.

In France, he has established large cohorts of patients infected with HIV: the ANRS CO 03 cohort, which has been followed for the last 30 years, or the cohort of patients co-infected with HCV and HIV (ARNS CO13 HEPAVIH), followed for the last 12 years. However, most of his work involves Africa. He was joint supervisor of the pivotal trial ANRS 049 DITRAME, which in 1999 provided evidence for the efficacy of a short AZT treatment in reducing HIV transmission from mother to child in West Africa. Today, his research approach is aimed at achieving the “90-90-90” goals set by UNAIDS for controlling the epidemic all over the world: by 2020, 90% of people living with HIV will be diagnosed, 90% of people diagnosed will be receiving antiretroviral treatment, and 90% of people undergoing treatment will have their viral load under long-term control. With his South African colleagues, Prof. Dabis has thus sought to evaluate over the last five years, in a region badly affected by HIV, the efficacy of an original approach combining a repeated offer of home-based screening with rapid medical care for all people infected. The objective of this study was thus to reduce HIV transmission within the population of this region. The first results of the ANRS 12249 TASP (Treatment as Prevention) trial were made public at the last International AIDS Conference, in July 2016. These results, eagerly awaited by the international community, revealed the difficulty of putting such an approach in place in the field, and were inconclusive with respect to reducing the risk of HIV transmission in the population in the short term.

François Dabis chaired ANRS Coordinated Action 12, responsible for the Agency’s scientific programme in countries with limited resources, from 2002 to 2015. He has been a very regular member of WHO and UNAIDS expert committees tasked with drawing up international directives on HIV. For the last ten years he has been principal investigator of International Epidemiology Databases to Evaluate AIDS (IeDEA) West Africa, an international consortium that pools databases on the care of people living with HIV in these countries, and is funded by the US National Institutes of Health. In 2015-2016, following the Ebola epidemic and at the request of the French authorities, he coordinated the establishment of the RIPOST programme, an initiative to strengthen the ability of the national public health institutes in West Africa to respond to epidemic threats.

François Dabis chaired the scientific council of InVS (now Santé Publique France) from 2003 to 2012, and was a member of the French High Council for Public Health (HCSP) from 2011 to 2016. He is a Chevalier de la Légion d’Honneur (Knight of the Legion of Honour).

For the new Director of ANRS, “There are still many challenges for both basic and translational research today: fighting structural and individual obstacles to prevention, screening and treatment of HIV and hepatitis in France and in the Agency’s partner countries, developing a vaccine, eradicating HIV and HBV…” He adds, “I know ANRS well, and can testify to the vigour that this agency instils, and its ability to adapt to new challenges and support researchers in their projects.” He concludes that ANRS must maintain its commitment to achieving the health-related sustainable development goals, by expanding its areas of intervention. “It seems essential to me that our partnership with countries that have limited resources, and the know-how we have developed together for many years in the area of HIV, and more recently hepatitis, should be applied to other key health problems, especially those that are infection-related.”

Yves Lévy, Chairman and CEO of Inserm, is delighted at the appointment of Mr Dabis, and wishes to “salute the work accomplished by Jean-François Delfraissy at the head of ANRS, which helped to support French and international research teams working successfully in the area of HIV and hepatitis, with strong international visibility”.

Moving to summer time: how does it impact our health?

Heure d't la craie sur ardoise

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During the last weekend in March we moved to summer time.

During the night of Saturday into Sunday, we put our clocks forward one hour.

Does this change in the hour, whose benefit lies mainly in energy savings, have an impact on our health? Does it disturb our biological clock and the quality of our sleep?

Claude Gronfier, a neurobiologist and researcher at Inserm (Unit 1208), has shown that the biological functions of the body are regulated by the circadian rhythm, a cycle of 24 hours which is endogenous (altered by the body).

Read the information pack “Chronobiology, the body’s 24 hour clock”

Get the latest on sleep:

“Lack of sleep causes brain impairment in adolescents,” published on 8 March 2017.

 “Sleep at the bedside of immunity,” published on 27 April 2016.

See the information file “Sleeps and its disturbance” on the Inserm website.

Microbiota and food contaminants : a mycotoxin amplifies the genotoxic action of a gut bacterium

Darmflora

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Researchers at the French National Institute for Agricultural Research (Inra) and their partners[1] have done animal studies on the consequences of having a certain group of microbiota bacteria and a common food contaminant, deoxynivalenol (DON), present in the gut simultaneously. They show that the presence of this mycotoxin enhances the genotoxicity of the bacteria, i.e. it increases the number of DNA strand breaks in intestinal cells, a phenomenon that can lead to the emergence of malignant cells. This work raises the question of synergy between food contaminants and the intestinal microbiota with respect to the process of colorectal carcinogenesis.

The gut microbiota in humans contains some 100,000 billion highly diverse bacteria. One species, Escherichia coli, is very common, and contains different groups. E. coli group B2 bacteria produce a genotoxic substance, i.e. a product that damages the DNA of intestinal cells, known as colibactin. An increase has been noted in the number of group B2 bacteria in the gut microbiota of populations from industrialised countries.

Mycotoxins are the most common natural contaminants present in human and animal food. One of these, deoxynivalenol (DON), is produced by moulds from the Fusarium family, which mainly develop in cereals. The human populations in Europe and North America are widely exposed to it in their food. In France and Europe, exposure of some fractions of the population, especially children, exceeds the toxicity reference values for this toxin.

The Inra researchers and their partners conducted in vitro and in vivo animal studies to see what happened when colibactin-producing Escherichia coli and DON were simultaneously present in the gut.

In animals colonised with colibactin-producing bacteria and exposed to DON in their food, the DNA damage to intestinal cells was significantly greater, compared with animals not producing colibactin. They thus show that the presence of the mycotoxin enhances the genotoxicity of group B2 E. coli.

These first results provide new data regarding possible synergy between food contaminants and the gut microbiota. The researchers will continue to work to elucidate the mechanism involved in this enhanced genotoxicity in the presence of DON, and studies are planned to extend the observations up to an advanced stage of colorectal carcinogenesis.

[1] Inra’s partners in this work: (Inserm / Toulouse III – Paul-Sabatier University, National Veterinary School of Toulouse [ENVT])

The human embryo as you have never seen it

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© Institut de la vision

A team coordinated by Alain Chédotal, Inserm research director at the Institut de la Vision (Inserm/UPMC/CNRS) and Paolo Giacobini at the Jean Pierre Aubert research centre (Inserm/Lille University) have just made a series of new observations of the anatomy of human embryos from 6 to 14 weeks old. A feat made possible by combining two recent techniques in immunomarking and 3D microscopy and a technique making the tissues transparent. These discoveries are published in the journal Cell dated 23 March 2017.

Plunging into the heart of a living being. From drawing to reality. This is what Alain Chédotal and his colleagues have done using their new technique to explore the anatomy or embryos. In the journal Cell, they reveal new photos and three-dimensional films of several tissues and organs of human embryos and foetuses from 6 to 14 weeks old, inaccessible until now.

Medical textbooks contain plenty of pictures of embryos but we always see the same thing: to represent their organs, we rely only on drawings. And the moulded embryos kept in medical faculties are made of wax. It should be said that the models, until now, were based on thin sections observed under the microscope, requiring illustrators to assemble and interpret all the information to represent an entire organ. This process belongs to the past with the advent of new three-dimensional imaging methods. In practice, the authors of this work have succeeded in combining three techniques, immunofluorescence, tissue clarification and microscopic observation, to be able to publish the first real 3D images of embryo tissues and organs.

They first used immunofluorescence to mark the intact organs. This technique consists of using fluorescent antibodies that bind specifically to the proteins expressed by certain cells, making it possible to locate them. Next, to view the fluorescent signal, they made the embryo tissues transparent using a technique perfected in mice in 2011. To do this, they immersed the tissues in several solvents, enabling them to strip the membrane-bound lipids from the cells, so as to retain only their protein architecture/skeleton and allow light to pass through. Finally, once this work was completed, they used a special microscope with a thin light source. A laser beam two millimetres thick scans the transparent samples, making it possible to photograph each plane and then the 3D image of the organ is built by computer.

Imaris Snapshot

© Institut de la vision


3D image of embryonic human lung. Future bronchi and bronchioles (blue and green) are visible, as are also the blood vessels (red).

New observations available to everyone

Marking embryos using antibodies made it possible to reveal the presence of specific cells and to obtain images of the peripheral nervous system, vascular system, lungs, muscles and the urogenital system. “What we observed has confirmed existing data in embryology, but this is the first time that we have obtained real images of the organisation of tissues in so much detail. In particular, we have discovered things that it was not possible to see without specific marking. For example, we succeeded in distinguishing sensory nerves (that transmit sensory signals to the brain) from motor nerves (that are connected to muscles), which was previously impossible“, explains Alain Chédotal. Another discovery: the variability of the nerve pathways in the hands. The development of the principal nerves is conserved in all hands, but the small peripheral nerve pathways develop much more randomly between the left and right hands and between individuals. Finally, the last advantage emphasised by the researchers: “we are able to have an idea of the rate of cell growth for each organ by counting the fluorescent cells at different embryo ages“.

To make these data available to the widest audience, the team has created a dedicated internet site subsidised by the French Voir & Entendre [See & Hear] Foundation*. “Here we offer free access to our films and we will continue to add new ones as we produce them. We would also like other laboratories to be able to add to it from their own work. The aim is to make it an initial image bank to provide a complete 3D atlas of the human embryo during the first development trimester, with organ-by-organ searches possible. There is both an education objective but also a clinical purpose, particularly for surgeons that operate in utero and who in this way will have precise images of embryo tissues or their nervous and vascular system“, the researchers conclude.

* https://transparent-human-embryo.com/

Stimunity Signs an Exclusive License Agreement with Institut Curie and Inserm

Paris, March 21st, 2017 – Stimunity, Institut Curie and Inserm are pleased to announce that the company has signed an exclusive worldwide license agreement on two key patents that cover Stimunity’s core technology VLP-cGAMP to develop new drugs in immuno-oncology.

All started with a fundamental discovery made by the laboratory Innate Immunity at Institut Curie, leads by Dr. Nicolas Manel, Senior Researcher at Inserm and co-founder of Stimunity. He discovered that viruses, when they infect healthy cells, can encapsulate a molecule that acts like a Trojan horse and triggers the defenses of the immune system. This discovery was protected and covered by two major publications in the scientific journal Science[1]. “This discovery gave us the idea of using a synthetic and inoffensive virus-like particle (VLP) that encapsulates the Trojan horse molecule and drives a very efficient immune response against tumor cells. This was the starting point of the project” explains Dr. Manel.

“From a discovery to a drug that can be used in human, there is so much work to do. That’s why we have decided with Nicolas to join our forces and to create a startup company” says Sylvain Carlioz, co-founder and CEO of Stimunity. The project was supported since the beginning by the Technology Transfer Office (TTO) of Institut Curie. “The scientific rational was validated by Dr. Sebastian Amigorena, Director of the Institut Curie – INSERM “Immunity and Cancer” research unit and also by the Institut Curie International Scientific Advisory Board member, Pr. Alain Fischer. From a business perspective, there was no doubt that the creation of a dedicated start-up to fully develop the potential of the patented technology was the best option” says Dr. Amaury MARTIN, Director of the TTO at Institut Curie and Director the Institut Carnot Curie-Cancer. “It also perfectly fits with the new strategy of the TTO that we want to promote and illustrate the potential of the Institut Curie Cancer Immunotherapy Center to be opened in 2017.”.

The license agreement comes together with an R&D Agreement between Stimunity and Nicolas Manel’s laboratory. It will allow the company to finalize the validation of the mechanism of action of the drug, necessary to convince private investors to lead a first seed round of 2 to 5M€. This money will cover the manufacture of the drug at GMP standards and the efficacy package on pre-clinical models, two elements needed before we can enter into clinical trials by the beginning of 2019. 

[1] Gentili M, et al. Transmission of innate immune signaling by packaging of cGAMP in viral particles. Science. 2015. Bridgeman A, et al. Viruses transfer the antiviral second messenger cGAMP between cells. Science. 2015.

Gender discrimination also exists in science

At university lecture

© Fotolia

 

Gender discrimination can be found in quite unexpected places. An international team that includes Demian Battaglia, a CNRS Researcher at the Neurosciences Systems Institute (INS) (Inserm/Aix-Marseille University), and researchers from Yale and the Max Planck Institute (Germany) has just demonstrated that women are under-represented in the review process for scientific publications. This research is published in the 21 March 2017 issue of the journal eLife.

Gender discrimination is a well-known phenomenon. Scientific research is not spared by these issues, including academic publication, one of the cornerstones of scientific endeavour. In order to be validated, every article must be approved by independent researchers. Obviously, these reviewers are meant to be selected according to their competences and not their sex. An international team has focused on the question of the gender of these reviewers. The results are shocking: women scientists, already a minority in their field, are under-selected for reviewing papers. The blame falls on the natural and unconscious tendency of editors, mainly male, to choose someone of their own sex.

Demian Battaglia, a CNRS researcher at the Neurosciences Systems Institute (INS) (Inserm/Aix-Marseille University), and Markus Helmer and his colleagues worked on journals from Frontiers, the only publishing house to publicly disclose the names of reviewers. After studying 41,000 publications in different areas (science, health, engineering and social science), published between 2007 and 2015, and a database of 43,000 reviewers, they found that women are under-represented in various scientific areas. But they are also asked to provide reviews less often than might be statistically expected.

The reason is simple: editors, be they men or women, have a tendency, known as homophily, to select reviewers of their own sex. The practice is common in friendships and the professional network. But it manifests itself in different ways for the different sexes. This behaviour is widespread in men (over 50% of individuals), and limited, but practised in an extreme manner, in women (about 10% of female editors are strongly homophilic).

The result of this process is that even where there is a policy of parity, with equal representation of women and men, the authors believe that this homophilic bias may persist. The real challenge is therefore to change these behaviours. The authors of the study thus propose tools, such as tables that would be posted when proofs are published online, recalling the figures on sexism.

The team now hopes to repeat its analyses in a few years in order to see if its recommendations have been adopted.

Friday 24 March: World Tuberculosis Day

Macrophages colonisés par Mycobacterium tuberculosis

Macrophages colonisés par Mycobacterium tuberculosis © Denis Fenistein-Priscille Brodin (Inserm)

According to WHO, tuberculosis is one of the 10 main causes of death in the world. In 2015, 10.4 million people were suffering from this illness and 1.8 million died. Furthermore, tuberculosis is the main cause of death in people who are HIV positive.

 According to WHO, a third of the world population has latent tuberculosis. In 5 to 10% of cases, the Koch bacillus (mycobacterium tuberculosis) becomes active, particularly in people whose immune systems are compromised and who have a much higher risk of developing the disease.

Faced with this major health problem, Inserm researchers are getting together to advance the research, particularly with the issue of multi-resistant strains of the agent to antibiotics.

Researchers from Inserm Unit 1019 at the Lille Centre for Infection and Immunity

(CNRS/Institut Pasteur Lille/Inserm/University of Lille) have invented a prototype drug SMARt-420 that can eliminate resistance to ethionamide, an antibiotic used to treat tuberculosis.

Read the press release “Tuberculosis and antibiotic resistance: researchers In Lille invent a new prototype drug,” published 16 March.

See the information pack on tuberculosis, devised in collaboration with Camille Locht, microbiologist and Director of the Lille Centre for Infection and Immunity, Inserm Unit 1019 (CNRS/Institut Pasteur Lille/Inserm/Lille University).

A team of researchers from the Lille Centre for Infection and Immunity (CNRS/Institut Pasteur Lille/Inserm/Lille University) and from the Institute of Systematics, Evolution and Biodiversity (CNRS/National Museum of Natural History/UPMC/EPHE) is interested in the evolutionary history of the mycobacterium responsible for tuberculosis, particularly the so-called Beijing lineage associated with the propagation of multidrug resistant TB in Eurasia.

See press release: “The origins of multi-drug resistant strains uncovered,” published 19 January 2015.

What if optimism were learnt?

How does our brain learn from our mistakes? Does it prefer good news to bad news? These are the questions answered by a team of researchers led by Stefano Palminteri (Inserm-ENS), laureate of the ATIP-Avenir programme, from the Laboratoire de Neurosciences Cognitives. The results will be published in Nature Human Behaviour.

Generally speaking, humans tend to overestimate the likelihood of a positive event in the near future, whereas they underestimate that of a negative event. In cognitive psychology, this is known as the optimism bias. This and other cognitive biases influence our rational logic, our judgements and our decisions, and hence our behaviours. Optimism bias is a tendency to take “positive” information (good news) into account more than “negative” information (bad news). This basic asymmetry is assumed to generate and reinforce this bias, and leads us to believe that our future outlook is, on average, better than that of others. This has particularly been shown in heavy smokers who underestimate their risk of premature death, and in certain women who underestimate their risk of getting skin cancer.

A research team from the Laboratoire de Neurosciences Cognitives (LNC) wished to know more about this phenomenon and understand its origin. Is this phenomenon linked only to our beliefs regarding possible future events, or more generally, is it also present in any type of learning, including the most basic: learning by trial and error? To do this, the researchers studied behaviour in a group of people involved in a process of learning by trial and error, which consisted of choosing between two symbols associated with a monetary reward. Depending on the choice of the participant, the latter could win €0.50 (“good news”), win nothing, or lose €0.50 (“bad news”). Results demonstrated that the participants attributed 50% more importance, on average, to the “good news” than to the “bad news.” This general tendency of our brain to learn in an asymmetrical manner, preferring the good news and ignoring the bad news, may be the basis for the optimism bias.

One question remained unanswered, that of the relationship between this deeply rooted learning bias and the brain reward circuits. To answer this question, the LNC researchers studied the brain activity of subjects carrying out the learning task just described, using functional magnetic resonance imaging (fMRI). According to Stefano Palminteri, who headed this study: “The brain activity recorded in the main structures of the brain reward circuit is almost twice as high in an optimistic subject compared to a more realistic subject, for the same monetary reward. This activity shows the existence of distinct profiles, more or less optimistic or realistic.”

Apart from providing a neuropsychological explanation for optimism, this work provides additional evidence for the existence of a deeply rooted learning bias in human cognition. The optimism bias could therefore be involved in psychopathologies such as depression (absence of the bias) or certain addictions (overexpression of the bias). “In order to better understand the cause and persistence of these behaviours, with their high social and human cost, it is therefore essential to study of these basic biases in the learning,” the authors of the study believe.

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