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A research team consisting of Tsutomu Kobayashi, Ichiro Hasuo, Fuyuki Ishikawa, and Shinya Katsumata at the National Institute of Informatics (NII, Japan) and Rick Salay and Krzysztof Czarnecki at University of Waterloo (Canada) developed a method that automatically transforms models of controller software into models that satisfy safety requirements even when there is uncertainty in sensing the state of the environment. In addition to the transformation, the method generates formulas that represent the degree of uncertainty that the controller software can tolerate. The method can be applied to various controller systems that interact with the external environment, including autonomous vehicles.

This research was conducted under the ERATO MMSD Project (*1) funded by the Japan Science and Technology Agency (JST, Japan). The findings were presented at the 13th NASA Formal Methods Symposium (online) on May 26th, 2021.

Background

Controller systems such as drones and autonomous vehicles are vital in society. These systems must be able to function as safely as possible because many of them are intended for use in the real world. Approaches involving mathematical modeling of the systems and verifying their safety are effective for guaranteeing safety.

The controller software in such systems determines its actions in response to the state of the environment, which is perceived with sensors. In reality, however, the systems may perceive values that differ from the true values (perceptual uncertainty). This can cause safety violations if the controller software behaves in response to the incorrectly perceived values. For instance, if the sensor of an autonomous vehicle can misperceive the positions of other cars up to 1 m, it should operate with a safety margin of at least 1 m (Figure 1 (a)).

Designing such uncertainty-aware and safe controller software is quite complicated because developers need to verify that safety is guaranteed for every possible behavior of the system while taking into consideration differences between true values and perceived values (Figure 1 (b)). In addition, it is difficult to estimate the degree of the uncertainty. For example, perceptual uncertainty depends on the situation in which the controller system is deployed, such as whether or not it is foggy. Therefore, rather than specifying concrete perceptual uncertainty in models, constructing uncertainty-unaware controller models and calculating the degree of uncertainty the constructed controllers can tolerate are more suitable for flexible analysis. However, obtaining this limit as a formula proved to be difficult.

Methods and Results

In this study, we propose a method that automatically transforms a model of an uncertainty-unaware controller into a model of a robustified controller, that is, a new controller that safely behaves even under uncertainty (Figure 2).

The method consists of two steps.

The first step (uncertainty injection) is to transform an input model of an uncertainty-unaware controller into an intermediate model of an uncertainty-aware controller. Note that the behavior of the intermediate model is the same as that of the input model so it is unsafe.

Then the next step (robustification) is to transform the intermediate model into one that is uncertainty-aware and safe. The behavior of the resulting controller is updated so that it operates safely even under uncertainty.

In addition, the method generates a formula that represents the degree of uncertainty that the output controller can tolerate.

In the first step (uncertainty injection), variables of perceived values, which can differ from true values, are introduced. Moreover, while the input model is specified under an ideal assumption that the controller can refer to the true value when it determines an action, the intermediate controller refers to the perceived value to reflect the reality of the perception. Although the intermediate controller determines its actions in response to perceived values, safety is not guaranteed because its behavior is the same as that of the input controller. For example, an autonomous vehicle may misperceive the distance to another car as 5 m when it is only 4 m, resulting in a collision.

In the second step (robustification), the case distinction of the state of the environment is calculated. For instance, in some situations, an autonomous vehicle may be unsure of whether it should cruise or brake due to perceptual uncertainty about the distance between itself and a car ahead. The robustification method exhaustively lists such uncertain cases so that they are considered separately. In addition, the behavior of the controller is updated so that safety will be guaranteed even under perceptual uncertainty. The method considers all possibilities of the true value estimated from the perceived value and calculates behavior that is safe for every possibility.

Constraints on the behavior of the generated controller are specified so that it is guaranteed to operate safely even under uncertainty. However, whether such constraints are satisfiable depends on the uncertainty. As an extreme example, if a sensor misperceives the positions of other cars up to 100 km, then guaranteeing safety is impossible in many situations. This raises the question of how much uncertainty the generated controller can tolerate. Where is the limit?

To answer this, the proposed approach also generates the limit as a formula of uncertainty. Developers can choose appropriate sensors from a given catalog by using the formula as the criterion. In addition, the formula can be used to analyze uncertainty, such as how the uncertainty will be propagated if the controller is combined with other components.

The method makes the construction of uncertainty-aware and safe controllers more systematic and effortless. Moreover, it enables developers to flexibly analyze various situations of perceptual uncertainty. Thus, the method improves the overall safety of the real world in which controller systems are implemented ubiquitously.

Future outlook

In addition to autonomous vehicles, the proposed method can also be applied to various other controller systems that interact with external environments. In future work, we intend to generalize the method so that it will be able to deal with a broader range of uncertainty. For instance, we will tackle misclassification problems such as an object classifier module classifying an object as a wrong object class.

Comments from Tsutomu Kobayashi

"Controller systems are crucial because most software systems' usefulness is due to their interactions with external environments. This research aims to help developers apply formal modeling approaches to realistic software by addressing the inevitable problem of controller systems regarding the gap between the perception and reality. Thus, developers can focus on the essence of controller behavior. We believe that the method is valuable and can be extended in various ways. We will continue working towards the systematic and easy application of rigorous mathematical methods to ensure a safe environment for everyone."

Information on Paper

Title

: Robustifying Controller Specifications of Cyber-Physical Systems Against Perceptual Uncertainty

Authors

: Tsutomu Kobayashi, Rick Salay, Ichiro Hasuo, Krzysztof Czarnecki, Fuyuki Ishikawa, Shin-ya Katsumata

Conference

: The 13th NASA Formal Methods Symposium https://shemesh.larc.nasa.gov/nfm2021/

Date of Presentation

: May 26th, 2021 (US Eastern Time)

(*1) ERATO Hasuo Metamathematics for Systems Design Project (ERATO-MMSD): a project funded in the Exploratory Research for Advanced Technology (ERATO) scheme of the Japan Science and Technology Agency (JST). The project conducts academic research for quality assurance of cyber-physical systems as the core of Society 5.0. The project specifically focuses on automated driving systems and investigates reliability techniques for modeling, formal verification, testing, and holistic, practical V&V techniques including all of them. This challenge requires tight collaboration of different academic areas such as software science and engineering, control theory and engineering, and artificial intelligence. Therefore, the project also focuses on (meta)mathematical theories. https://www.jst.go.jp/erato/hasuo/en/

Philadelphia, July 7, 2021 - Tourette syndrome, a neurodevelopmental disorder, causes motor and phonic "tics" or uncontrollable repeated behaviors and vocalizations. People affected by Tourette syndrome can often suppress these tics for some time before the urges become overwhelming, and researchers have long wondered at the neural underpinnings of the suppression effort.

Now, in a new study using a non-invasive technique to measure brain activity called high-density electroencephalography (hdEEG), researchers at Yale School of Medicine have assessed the impact of tic suppression on functional connectivity between brain regions.

The study appears in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, published by Elsevier.

"Tic suppression is an important feature of Tourette syndrome. Understanding how someone may temporarily gain control over their tics may inform several research areas in Tourette syndrome. Yet, brain correlates of tic suppression have not been studied extensively, especially in children," said Denis Sukhodolsky, PhD, senior author of the study, and Associate Professor at the Yale Child Study Center at the Yale School of Medicine, New Haven, CT, USA.

Cameron Carter, MD, Editor of Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, said of the study, "Understanding brain mechanisms associated with successful coping in disorders such as Tourette syndrome opens up opportunities for developing targeted treatments to enhance the innate self-control that normally emerges as the brain matures."

The team led by Dr. Sukhodolsky recorded the brain activity of 72 children, aged 8 to 16 years old, with Tourette syndrome using hdEEG, while they were ticcing freely and while they were suppressing their tics. The researchers then assessed connectivity between the different regions in the brain.

The authors found that connectivity between multiple brain regions was increased while children suppressed their tics. "Some of these regions are part of the default mode network, an array of brain regions engaged during internal thought processes such as daydreaming," explained first author Simon Morand-Beaulieu, PhD.

Additionally, the researchers reported that functional brain connectivity during tic suppression was positively correlated with age, suggesting that the brain networks of tic suppression undergo developmental changes in response to the experience of tics. "This increase in functional connectivity as children mature is consistent with increasing tic suppression capacities developing into adolescence as well as a better awareness of the sensory phenomena accompanying tics," said Dr. Morand-Beaulieu.

The study highlights the brain mechanism involved in a temporary decrease in tic frequency, which could have therapeutic implications. "It will be important to assess whether the same mechanism plays a role in a more structured intervention to decrease tic severity, such as behavioral therapy for Tourette syndrome," said Dr. Sukhodolsky.

Researchers at Karolinska Institutet in Sweden publish new findings in the journal Cancer Discovery showing how pharmacological activation of the protein p53 boosts the immune response against tumours. The results can be of significance to the development of new combination therapies that will give more cancer patients access to immunotherapy.

Given its ability to react to damage to cellular DNA and the key part it is thought to play in preventing tumour growth, the protein p53 has been dubbed the "guardian of the genome". Half of all tumours have mutations in the gene that codes for the protein, and in many other tumours, p53 is disabled by another protein, MDM2.

It has long been known that p53 is able to silence certain sequences in our genome called endogenous retroviruses (i.e. DNA elements evolutionarily inherited from viruses), thus preventing genome instability. The researchers now show that the protein can also activate these sequences in cancer cells, leading to anti-tumour immune response.

"This was an astonishing discovery. When we blocked the suppressor MDM2, p53 activated endogenous retroviruses which induced antiviral response and boosted the production of immune-activating interferons," says lead investigator Galina Selivanova, Professor at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet.

The results were obtained when the researchers blocked MDM2 in mouse models using a substance coded as ALRN-6924 from the US company Aileron Therapeutics. The increase of interferon response was also seen in tumour samples from two patients taking part in the company's clinical trials of ALRN-6924.

"This shows that there are synergies that should be exploited between substances that block MDM2 and modern immunotherapies," Professor Selivanova continues. "A combination of these can be particularly important for patients who don't respond to immunotherapy."

Immunotherapy, or immuno-oncology, is described as a revolution in modern cancer treatment in the way it triggers the body's immune system to fight cancer cells. However, it does not work with all patients, and the presence of interferons could be a biomarker for whether or not immunotherapy will prove efficacious.

"If we can increase the level of interferons, we can therefore increase the chances that the immunotherapy will succeed."

Professor Selivanova is a pioneer in research on how mutated p53 can be re-activated using special molecules, one of which, APR-246, is undergoing clinical studies under the name Eprenetapopt at Aprea Therapeutics, a company that she co-founded.

"We now want to examine if Eprenetapopt produces the same interferon boost and can have the same potential to increase access to immunotherapy for patients with severe forms of cancer," she says.

The Mid-infrared lasers (MIR) with high peak power and high repetition rate operating in the range of 2.7~3 μm have important application in laser surgery and optical parametric oscillator (OPO).

A recent study conducted by SUN Dunlu's research group at the Hefei Institutes of Physical Science(HFIPS) of the Chinese Academy of Sciences (CAS) achieved high power, high efficiency and quasi-continuous mid-infrared laser in the free running and langasite [La3 Ga5 SiO14 (LGS)] Q-switched modes by using the Er3+ ions-doped YAP crystals as laser gain medium.

Based on their previous research work on laser, the researchers further improved the laser performance of Er:YAP laser crystal by laser-diode (LD) side-pumping method, a Er:YAP crystal rod with concave end-faces was used to compensate the thermal lensing effect. The maximum output powers of 26.75 W were achieved at 250 Hz, and 13.18 W at 1000 Hz, which is the highest working frequency in all the LD side- pumped Er-doped MIR laser so far.

In addition, they demonstrated a LD side-pumped and electro-optical Q-switched Er,Pr:YAP laser with emission at 2.7 μm. A giant pulse laser was obtained with pulse energy of 20.5 mJ, pulse width of 61.4 ns, and peak power of 0.33 MW at the highest working frequency of 150 Hz.

These results indicate that the Er3+-doped YAP crystals are promising candidate for the high power and high frequency mid-infrared laser device, which possess great potential for the application of dental ablation surgery and OPO pump source.

In 2016, researchers from the EDDyLab - Evolution & Diversity Dynamics Lab - at the University of Liège (Belgium) proposed a new definition of the geological boundary between the Devonian and Carboniferous periods (359 million years). This new definition has been tested by hundreds of researchers around the world and the results are now compiled in a special issue of the journal Palaeodiversity & Palaeoenvironments.

Geological time is divided into periods (Cambrian, Carboniferous, Jurassic, etc.), together covering the 4.6 billion year history of the Earth. The many climatic, environmental and biological changes that have punctuated this history are recorded in the rock layers, forming an incredibly rich archive of the Earth's past. "The study of these successive layers allows us to recognise the boundaries between these different periods, each boundary being defined by a specific event or 'marker', such as an extinction event or a change in climate," explains Julien Denayer, a palaeontologist at the EDDyLab and first author of the article. A locality is then designated, making the rocky successions of this particular place the international reference for this transition. "It was in Belgium, in the 19th century, that numerous divisions of the time scale were defined, such as the Frasnian, Tournaisian, Viséian, Namurian, etc... These references are still used today on an international scale.

The boundary between the so-called Devonian and Carboniferous geological periods (359 million years ago) was the first to be formally defined in 1927. The fossils marking the boundary were too rare in the rocks, so this definition was of little use. A second attempt was proposed fifty years later, but was also invalidated by the International Commission of Stratigraphy, the scientific body that establishes and validates the subdivision of geological time, again because of the scarcity of boundary fossils.

For the past ten years or so, palaeontologists and geologists specialising in the Devonian and Carboniferous periods have been working on redefining this boundary," says Cyrille Prestianni, palaeontologist at ULiège and co-author of the article. In 2016, we proposed a new definition, this time based on several contemporary phenomena, well recorded in the rocky successions of Wallonia. "According to the ULiège researchers, the boundary between these two periods is defined by the so-called Hangenberg Sandstone event - an episode of abrupt fall in sea level - which is also marked by a major extinction that decimated typical Devonian ecosystems such as coastal marshes and reefs. In ecological terms, this extinction was greater than the extinction of the dinosaurs at the end of the Cretaceous!

Since then, researchers around the world have tested the applicability of this criterion for defining the boundary. The results of these years of research are now compiled in a special volume of the journal Palaeodiversity & Palaeoenvironments. The EDDy Lab researchers publish an exhaustive review of the geological and palaeontological knowledge of the Devonian-Carboniferous boundary in Wallonia and the surrounding regions. In this publication, the members of the EDDy Lab were able to propose a scenario explaining the ecological and climatic crisis that caused the extinction of the Devonian fauna and flora. Our work is not yet finished," says Julien Denayer, "the next step is to select a new type locality. Several Walloon sites are now being studied using state-of-the-art techniques with a view to being proposed to become the world reference for the Devonian-Carboniferous boundary! »

Scientists from Tohoku University and the University of Maryland have pinpointed the strong magnetic field of the early sun as the reason behind the radial variation of rock and metal in rocky planets' cores. This magnetic field, which pulled small iron grains inward, explains Mercury's big iron core and why Mars has so little iron in its core.

The details of their research were published in the journal Progress in Earth and Planetary Science on July 5, 2021.

Planets have iron cores surrounded by a rocky shell, mostly made up of mantle and a thin skin of crust. The four inner planets of our Solar System, Mercury, Venus, Earth, and Mars have their own distinctive size and density. These differences have long since puzzled scientists.

Mercury has a metallic core making up about 3/4 of its mass, with the remaining 1/4 being a rocky silicate shell. The cores of Earth and Venus possess a metallic core of only 1/3 of their mass, with the rest being rock. Mars has a measly core comprising only 1/4 of its mass.

These radical changes in metal content offer clues about what controlled the distribution of raw materials in the early formation of the solar system.

During this period, swirling gas and dust cloud drew matter into the Solar System's center, thus forming the Sun. The rapid delivery to the center caused many collisions and heated the inner region of the Solar System. When the Sun was big enough to have its own internal gravity, it caused its proton-rich core to ignite its nuclear fuel, brightly turning on the Sun. Following this, the Sun's core began convecting, creating a dynamo generating a strong magnetic field.

The high temperatures of the inner Solar System turned elements into a vapor state. As the element cloud cooled down it rained out mineral compounds. Evidence from primitive meteorites reveals the compounds precipitated were either silicates or metals. The sun's magnetic field pulled the metal particles inwards.

The composition of inner rocky planets is remarkably similar to primitive meteorites. Also known as chondrites, these meteorites are jumbled mixtures of rock and metal in different proportions. Unlike rocky planets, they do not have cores.

The raw materials making up the rocky planets are just four unevenly distributed elements: oxygen, iron, magnesium, and silicon. This represents about 93% of a rocky planet's mass. Around 70% of that is equal measure oxygen and iron, whilst the rest consists of equal measure magnesium and silicon.

"Planetary cores are a big deal," proclaims coauthor of the study Bill McDonough. "They control where elements end up in the planet." McDonough points to the Earth's abundance of the nutrient phosphorus concentrated in its core as an example. "Planetary habitability also depends upon the size and compositions of its core in addition to the lifetime of its dynamo."

The core's dynamo generates a magnetic shield that protects us from cancer-causing cosmic rays. Once Mars lost its core dynamo, its surface water disappeared quickly thereafter.

Early on in Solar System formation, a cloudy disc of gas and dust surrounded the Sun and planets, serving as a conduit for the Sun's magnetic field. The strength of the magnetic field weakened as it got further away from the Sun. Mercury formed in the prime location - close to where the Sun's magnetic field was strongest, thus explaining its large iron core.

The study is the first on epidemiology and causes of traumatic brain injury in over 20 years. The research team reports in the journal BMJ Open of 4 June 2021.

Falling and cycling without a helmet are common causes

From a minor fall on a bicycle to a serious road traffic accident: The causes of a traumatic brain injury are manifold. About 90 percent of the approximately 270,000 cases per year are classified as mild, ten percent as moderate or severe. Current findings show that traumatic brain injury is increasing in the age group of over-65s. The research team at BG Kliniken in Bochum, Hamburg, Berlin, Halle, Frankfurt, Ludwigshafen and Murnau found that there has been a shift in the age group most frequently affected and that there is a discernible correlation between the severity of a traumatic brain injury, age and cause.

The study shows that the most frequent causes of traumatic brain injury are falls and no longer road traffic accidents. There has also been a shift with regard to road traffic accidents: The largest group here is no longer car occupants, but cyclists without helmets.

"We are registering a clear shift in the majority of the affected age group towards the older generation. This phenomenon can be observed in almost all industrialised countries," explains Professor Peter Schwenkreis, senior physician at the Neurological Clinic at Bergmannsheil. A link with the age of those affected is also discernible. Falls are the most common cause, especially among older women and men. "Older people are significantly more prone to falls and thus suffer a traumatic brain injury more quickly than other age groups. In addition, the severity of the injury is higher in these patients", Schwenkreis specifies. "This also explains why we are seeing an increase in deaths caused by such an injury in this age group."

Study with over 3,500 participants

For the study, a neuroscientific research group of the BG Kliniken observed and evaluated the development, treatment and impact for patients with traumatic brain injury. A total of 3,514 patients were included in the study. All of them were treated at one of the participating BG Kliniken between 1 October 2014 and 30 September 2015. The prerequisite was that the medical care had taken place within the first 24 hours after suffering the traumatic brain injury.

The results were collected using two different methods: Evaluation of documentation forms from initial care to rehabilitation on the one hand, and standardised telephone interviews with the affected persons three and twelve months after they suffered the trauma on the other hand. A study of this magnitude on the epidemiology of traumatic brain injury has not been published in Germany since 2000/2001.

Simple measures can have a big impact

As moderate to severe traumatic brain injuries occur more frequently in older people, the research group identifies a specific need for more prevention work here. "Training measures for safe walking, training in the use of walking aids or redesigning the home by removing tripping hazards are conceivable. As simple as these measures sound, they can prevent serious injuries", says Peter Schwenkreis. "The advances in passenger protection in cars have had a clearly demonstrable effect", he explains further. "Now it is important to implement the protection of pedestrians and cyclists as part of the emerging shift in mobility."

Traumatic brain injury

A traumatic brain injury is any injury to the skull, with or without fracture, that involves damage to the brain. Just like the causes, the symptoms can also be very diverse. They range from headaches, dizziness and lightheadedness to amnesia or impaired consciousness. However, even minor injuries to the skull can cause bleeding or swelling the brain, which is why a traumatic brain injury should be assessed immediately after an accident.

Together with their multifaceted action mechanisms, activation-induced cytidine deaminase (AID) and so-called APOBEC proteins are important factors in the body's immune response and offer fast and effective protection against a large number of DNA and RNA viruses. The task of AID is to strengthen the human immune response, while APOBECs are able to block the virus. A MedUni Vienna research team comprising Anastasia Meshcheryakova, Diana Mechtcheriakova and Peter Pietschmann from the Institute of Pathophysiology and Allergy Research has now addressed the potential interrelations between AID/APOBECs and the SARS-CoV-2 virus, particularly in connection with the course of COVID-19 in different patients. This could provide a starting point for future clinical strategies to improve and strengthen individual antiviral response.

The defence mechanisms associated with AID/APOBECs in response to the coronavirus were assessed on the basis of integrative data mining and gene expression analyses, as part of a study conducted with international partners. It was found that members of the APOBEC family are preferentially expressed in a particular type of cell or tissue: "However, this does not mean that a particular cell type only expresses a particular member of the APOBEC family but that each cell type exhibits its own characteristic APOBEC repertoire," explains Diana Mechtcheriakova.

What is completely new is that the researchers found that APOBEC4 is highly expressed in cells and tissues that are points of attack for SARS-CoV-2. These include epithelial cells in the bronchi, in the lungs, in the trachea and in the nose. It was also found that there is an extremely high level of expression of both molecules (one of the members of the APOBEC family and ACE2, the entry receptor for SARS-CoV-2), in the gastrointestinal tract, in the heart and in the testis.

"Based on this knowledge, the clinical challenge in the future will be to characterise the antiviral cell status attributed to AID/APOBECs specific to patients and/or patient groups and to correlate the cell-type-specific AID/APOBEC gene expression signature with the organs affected by SARS-CoV-2 infection and the severity of COVID-19," explains Mechtcheriakova.

A particular role in this process is attributed to AID, since it co-determines the strength of an adaptive immune response. "The AID-driven, highly coordinated sequence of events, which all occur in specialised immunological lymphoid structures with germinal centres, results in the production of high-affinity antibodies by plasma cells or memory B cells. These antibodies are directed against the pathogen causing the disease, such as SARS-CoV-2, either in the course of infection or of an immune response to a vaccine," explains Anastasia Meshcheryakova. The role of these complex lymphoid structures and of AID is of great importance for our further understanding of the pathobiology of COVID-19, and consequently for the development of new therapeutic approaches.

Sleep deprivation - from lifestyle choices, pandemic stress, or late-night computer study - can quickly lead to loss of energy and function during the day and even feelings of anger and depression, an Australian sleep institute study has shown.

The study, led by Flinders University, asked 34 health teenagers (20 males) aged between 15 and 17 to spent 10 days and nine nights in a specially designed sleep centre.

They were allocated to one of three sleep 'doses' for five consecutive nights- from five hours, 7.5 hours, or 10 hours in bed per night - with two baseline and two 'recovery' nights of up to 10 hours' time in bed.

Their mood was measured every three hours after waking up to assess responses to feelings such as 'depressed', 'afraid', 'angry', 'confused', 'anxious', 'happy' and 'energetic'.

Using unipolar visual analogue scales measuring the mood states, the study found:

Participants in the five-hour group, but not the 7.5- or 10-hour groups, reported being significantly more depressed, angry, and confused during sleep restriction than at baseline

Happiness and energy decreased significantly following sleep restriction to five hours' sleep opportunity

When the participants had 10 hour sleep opportunities, their happiness significantly increased

No statistically significant effects of sleep restriction were found for fear or anxiety, although small-to-moderate effects of sleep restricted to five or 7.5 hours were found.

"The two nights of recovery sleep was not sufficient to recover from increased negative mood states for the five-hour group, although recovery occurred for positive mood states," says lead author Flinders University research fellow Dr Michelle Short.

"Given the prevalence of insufficient sleep and the rising incidence of mood disorders and dysregulation in adolescents, our findings highlight the importance of sufficient sleep to mitigate these risks."

The article, Sleep duration and mood in adolescents: an experimental study (2021) by SA Booth (CQU), MA Carskadon (US), R Young and MA Short, has been published in Sleep, Volume 44, Issue 5, May 2021, https://doi.org/10.1093/sleep/zsaa253

Adolescence is a critical maturational stage in terms of heightened risk of the onset of mood disorders, with researchers stressing that sufficient sleep crucial to guard against mood deficits in otherwise healthy adolescents.

The results of the experimentally manipulated sleep duration and mood study confirm that adolescents report deterioration in moods in terms of depression, happiness, anger, confusion and energy.

The relationship between experimentally manipulated sleep duration and mood in adolescents used mixed models analyses with adhoc comparisons.

Dysmenorrhea, that is, frequent severe and painful cramps during menstruation from abnormal contractions of the uterus, is the most common of all gynecological disorders. It affects between 16-91% of girls and women of reproductive age, of whom 2%-29% have symptoms severe enough to restrict their daily activity. Now, for the first time, researchers from China Medical University Hospital in Taiwan have shown that long-term exposure to air pollutants such as nitrogen and carbon oxides and fine particulate matter greatly raises the risk of developing dysmenorrhea. Based on long-term data on air quality and public health from national databases, they show that the risk to develop dysmenorrhea over a period of 13 years (2000-2013) was up to 33 times higher among Taiwanese women and girls who lived in areas with the highest levels of air pollutants compared to their peers exposed to lower levels of pollutants. These results were recently published in the open access journal Frontiers in Public Health.

A common debilitating disorder with no known cure

Dysmenorrhea can be due to hormonal imbalances or to underlying gynecological conditions such as endometriosis, pelvic inflammatory disease, ectopic pregnancy, or tumors in the pelvic cavity. Symptoms are often life-long: they include cramps and pain in the lower abdomen, pain in the lower back and legs, nausea and vomiting, diarrhea, fainting, weakness, fatigue, and headaches. In addition to reducing quality of life, dysmenorrhea also has a major socioeconomic impact, as females with dysmenorrhea may be temporarily unable to work, attend school, or engage in leisure activities. Dysmenorrhea has no known cure, but its symptoms may be managed with anti-inflammatory drugs and hormonal contraceptives.

"Research has already shown that women who smoke or drink alcohol during their periods, or who are overweight, or have their first period very young, run a greater risk of dysmenorrhea. Women who have never been pregnant are likewise known to be at greater risk. But here we demonstrate for the first time another important risk factor for developing dysmenorrhea: air quality, in particular long-term exposure to pollution. We don't yet know the underlying mechanism, but emotional stress in women exposed to air pollutants, or higher average levels of the hormone-like prostaglandins in their body, might be part of the answer," says one of the authors, Prof Chung Y. Hsu at the College of Medicine, China Medical University, Taichung, Taiwan.

The authors, led by Prof Chia-Hung Kao, the Director of the department of nuclear medicine and the Center for Positron Emission Tomography (PET) at China Medical University, studied de-identified health measures from a total of 296,078 women and girls (approximately 1.3% of the total population) between 16-55 years old. These data came from Taiwan's Longitudinal Health Insurance Database starting 2000 (LHID 2000), a representative subsample from Taiwan's nation-wide health insurance database.

The study sample exclusively included women and girls without any recorded history of dysmenorrhea before 2000. The authors looked for a long-term association between the risk of dysmenorrhea and air quality, in particular the mean exposure over the years to air pollutants - nitrogen oxide (NOx), nitric oxide (NO), nitrogen dioxide (NO2), carbon monoxide (CO), and particles smaller than 2.5 μm in diameter ('PM2.5') - obtained from the 'Taiwan Air Quality Monitoring Database' (TAQMD) of the Environmental Protection Agency.

Air pollutants are an important new risk factor

They found that from 2000- to 2013, 4.2% of women and girls in the studied sample were diagnosed with dysmenorrhea for the first time. As was expected from previous studies, younger women, women of lower incomes, and living in more urbanized areas tended to have a higher risk of developing dysmenorrhea over the study period. But importantly, the 'hazard ratio' (that is, the age- and year-specific risk) of developing dysmenorrhea increased by 16.7 to 33.1 fold for women and girls from the 25% of areas with the highest yearly exposure to air pollutants, compared to those from the 25% of areas with the lowest exposure. NOx, NO, NO2, CO, and PM2.5 levels each contributed separately to the increased risk, but the greatest individual effect was from long-term exposure to high PM2.5.

"Our results study demonstrate the major impact of the quality of air on human health in general, here specifically on the risk of dysmenorrhea in women and girls. This is a clear illustration of the need to for actions by governmental agencies and citizens to reduce air pollution, in order to improve human health," concludes Prof Hsu.

A study led by University of Barcelona researchers and carried out together with more than 1,650 students and their family members from 18 educational centres in Barcelona shows that citizen science is a valid approach able for doing high quality science, and in this case, able to provide nitrogen dioxide values with an unprecedented resolution and to assess the impact of the pollution in the health of their inhabitants.

The journal Science of the Total Environment has published the results of a study carried out by the research group OpenSystems of the University of Barcelona, the Barcelona Institute for Global Health (ISGlobal), promoted by La Caixa Foundation and the 4Sfera company, that shows the key role of citizen science in the relationship between the assessment of the exposure to air pollution and the collective action for the improvement of air quality.

The publication describes the xAire project, which involved the organization of collective data gathering in Barcelona regarding the concentration of nitrogen dioxide, a pollutant related to the motorized vehicles. This concentration was measured during a 1-month period between February and March 2018 thanks to the families with children aged between 7 and 18, from 18 public primary schools in the different districts of the city.

The results provide unprecedented information on the pollution of the air in the city with a notable precision. The location of the measuring spots was decided autonomously among the students and their families following the same scientific process. "xAire has not only shown the problems surrounding the schools and the neighbourhoods but it has also provided arguments to the families and schools to ask for improvements in their environment according to the data they gathered", notes Professor Josep Perelló, leader of the study and member of the Institute of Complex Systems of the UB (UBICS).

Air pollution in Barcelona, a serious and underestimated problem

The results of the research show a wide and representative distribution of nitrogen dioxide concentration levels of the city regarding population density. The study analysed very high levels, with an annual average of 49 μg/m3, above the thresholds of the European directive and the WHO, which are 40 μg/m3. More than 5% of the samples double the threshold value of 40 μg/m3, thus confirming that air quality is a serious problem in Barcelona. The measured levels also show large differences between districts and within the same district, depending on the street. The average values obtained in Ciutat Vella, Sants / Montjuïc, Les Corts and Horta / Guinardó by xAire are particularly worrying, as they are higher than those of the nearest official stations.

Improvements in a model of the pollution impact on health

The obtained data have also made it possible to obtain a more up-to-date and accurate estimation of the models for estimating the impact of NO2 on health used by the scientific community. Specifically, the study has estimated that 1,084 new cases of childhood asthma are attributable to NO2 each year in Barcelona, an equal figure to 48% of the total annual cases. According to Mark Nieuwenhuijsen, head of Urban Planning, Environment and Health Initiative of ISGlobal, "if we reduce NO2 levels, especially around schools, we could significantly reduce cases of childhood asthma".

A coordinated effort to measure pollution in 725 areas of the city

xAire was born with the aim to expand the detail and representativeness of the city's levels of pollution, provided by the city's seven official stations. The effort with more than 1,600 involved people has resulted in measurements of nitrogen dioxide in 725 locations. The number of obtained samples exceeds previous campaigns conducted by professional scientists, who gathered the concentration of nitrogen dioxide in a maximum of 200 locations simultaneously.

The xAire project returned the data to each school group and these are available publicly on an interactive map. The results were discussed in the schools mainly considering the WHO and EU limit values. The discussions showed a clear understanding of the follow-up data and the scientific research process.

Boys and girls aged between seven and eight were able to perfectly explain the scientific protocol and the meaning of the data in the InfoK of the Super 3 Channel, during the Science Congress, organized by the Barcelona Education Consortium and in front of the city mayor Ada Colau (Escola El Sagrer). The same schools provided the data to City Council officials along with a set of proposals based on scientific evidence, at an event held in Saló de Cent. The proposed measures range from the promotion of public transport in the neighbourhood and pedestrian routes to the need to cover part of the ronda de Dalt (Dolors Monserdà, Sarrià) or to accelerate the reform of Avinguda Meridiana (El Sagrer).

Large-scale citizen science campaigns on air quality should not be seen simply as a public awareness activity and an education program. "In this intense participatory component, citizens can be actors in research and not just recipients of a message. This approach to citizen science adds sophistication and diversity to the scientific research process, as it requires multidisciplinary professional scientists and the participation of non-academic organizations", says Isabelle Bonhoure, researcher at the OpenSystems Group of the UB.

Although hypomorph mammals (or equids) are currently represented by only one genus ('Equus') and just a handful of species of horses, donkeys and zebras, they were more diverse during the Eocene epoch (between 56 and 33.9 million years ago). One of the most widespread groups in Europe, which was an archipelago at that time, were the palaeotheriidae, named after the genus 'Palaeotherium', described in 1804 from fossils originating in the quarries of Montmartre (Paris) by the famous French naturalist George Cuvier.

The international Journal of Vertebrate Paleontology has recently published a paper on a study led by Leire Perales-Gogenola describing two new species of palaeotheriidae mammals that inhabited the subtropical landscape of Zambrana (Álava) 37 million years ago. Together with their collaborators from the UPV/EHU's Vertebrate Palaeontology research group, they described the new species 'Leptolophus cuestai' and 'Leptolophus franzeni', naming them in memory of the palaeontologists Miguel Ángel Cuesta from Palencia, and Jens Lorenz Franzen from Bremen, specialists in mammal fauna of the Eocene epoch in Europe.

Palaeotheriidae (or pseudo-horses) were represented across the European archipelago by more than half a dozen genera, more than half of which were endemic to the Iberian island, and became extinct during the climatic-biological crisis of the Eocene-Oligocene transition, also known as Stehlin's 'Grande Coupure'. Palaeotheriidae were mammals similar in terms of body shape to today's horses, but smaller in size. "Can one imagine animals similar to horses with three toes, the size of a fox terrier, a Great Dane and a donkey living in a subtropical landscape in Alava? Many of these pseudo-horses have been described at the Zambrana site," said one of the team members Dr Ainara Badiola. "Examples of them are the 'Pachynolophus zambranensis' and 'Iberolophus arabensis' species, which were first specified in this palaeontological enclave".

The two new species not only expand the fossil record and the biodiversity of palaeotheriidae fauna, but also display dental features atypical for equids of the Eocene. "Their molars have a very high crown and are covered with a thick layer of cementum. This type of dentition, also present in other endemic Iberian palaeotheriidae, could be indicative of a difference in environmental conditions between the Iberian and Central European areas, with more arid conditions or less dense or closed forests and the presence of more open areas in Iberia," explained Perales-Gogenola.

At the end of the Eocene in Europe, forests of an intertropical type gradually disappeared, giving way to plant communities of a more temperate type with more open areas. Modern horses or equids appeared in Europe later on during the Miocene (23-5.3 Ma). Their dentition, with very high crowns, is adapted for eating vegetation with a high grit content (grasses). The new species 'Leptolophus cuestai' from the Upper Eocene site at Zambrana (Álava) also displays molars with atypically high crowns, similar to those of some of the earliest equids in Europe.

In addition to its palaeobiological interest, the diverse fossil association of mammals from Zambrana, which comprises primates, rodents, marsupials, carnivores, artiodactyla and perissodactyla, provides new information on the climatic and environmental changes that occurred in Europe and in our environment over geological time.

The UPV/EHU's Vertebrate Palaeontology group is currently immersed in the description of more palaeotheriidae material, which could facilitate the description of new genera and species with unusual dental features among the equoid perissodactyla.

Big hydropower plants are an important source of clean and cheap electricity for many countries in Southeast Asia. However, dams harm the environment and have dire consequences on local communities. Building more dams would therefore pose major trade-offs between electricity supply and environmental protection.

A team of scientists based in Singapore showed that these two challenges can be decoupled. Their study, titled "Solar energy and regional coordination as a feasible alternative to large hydropower in Southeast Asia", recently published in Nature Communications, showed that there are more sustainable pathways to a clean energy future (refer to image).

Building on high resolution mathematical models of the Thai, Laotian, and Cambodian power systems, the team of scientists led by Dr Stefano Galelli from the Singapore University of Technology and Design (SUTD) demonstrated that future electricity demands and CO2 emission targets could be met with much less hydropower dams than currently planned.

In particular, the scientists found that only 82% of the planned dams in the Mekong River basin, a major biodiversity hotspot, are actually needed. In fact, it would be possible to halt the construction of all planned dams without major implications on the cost of electricity.

"The explanation behind these results lie in the cost and flexibility of other renewable technologies," said Dr Kais Siala, fromTUMCREATE Ltd. "The decreasing cost of solar energy is an essential factor of sustainable energy plans. Moreover, solar photovoltaic modules have the advantage of being scalable and deployable in any province of the Mekong countries".

"We have tangible opportunities for rethinking our regional energy plans," explained Dr Galelli. "So far, we have often prioritised the construction of big dams over the protection of our ecosystems. New technologies and their dropping costs provide us with concrete options for resolving this long-standing issue".

These findings are beneficial for many other countries striving to meet their energy demands without further imposing costly effects on their natural environments. From Southeast Asia to South America, many free-flowing rivers are being dammed to produce electricity. New developments in the power market could help us change the tide.

TAMPA, Fla. (July 6, 2021) - All it takes is three consecutive nights of sleep loss to cause your mental and physical well-being to greatly deteriorate. A new study published in Annals of Behavioral Medicine looked at the consequences of sleeping fewer than six hours for eight consecutive nights - the minimum duration of sleep that experts say is necessary to support optimal health in average adults.

Lead author Soomi Lee, assistant professor in the School of Aging Studies at the University of South Florida, found the biggest jump in symptoms appeared after just one night of sleep loss. The number of mental and physical problems steadily got worse, peaking on day three. At that point, research shows the human body got relatively used to repeated sleep loss. But that all changed on day six, when participants reported that the severity of physical symptoms was at its worst.

"Many of us think that we can pay our sleep debt on weekends and be more productive on weekdays," Lee said. "However, results from this study show that having just one night of sleep loss can significantly impair your daily functioning."

Data provided by the Midlife in the United States study included nearly 2,000 middle-aged adults who were relatively healthy and well-educated. Among them, 42% had at least one night of sleep loss, sleeping 1 ½ fewer hours than their typical routines. They recorded their mental and physical behaviors in a diary for eight consecutive days, allowing researchers to review how sleep loss causes wear and tear on the body.

Participants reported a pile-up of angry, nervous, lonely, irritable and frustrated feelings as a result of sleep loss. They also experienced more physical symptoms, such as upper respiratory issues, aches, gastrointestinal problems and other health concerns. These negative feelings and symptoms were continuously elevated throughout consecutive sleep loss days and didn't return to baseline levels unless they had a night sleep of more than six hours.

About one-third of U.S. adults sleep less than six hours per night. Lee says once that becomes a habit, it's increasingly difficult for your body to fully recover from lack of sleep, continuing the vicious cycle of worsening daily well-being, which could impact one professionally. A previous study led by Lee found losing just 16 minutes of sleep could impact job performance. Her previous findings also show that minor sleep loss can decrease daily mindfulness, which is a critical recourse for managing stress and maintaining healthy routines.

Lee says the best way to maintain a strong daily performance is to set aside more than six hours to sleep every night.

Announcing a new article publication for BIO Integration journal. In this article the authors Daowei Lin, Zhixiao Han, Yanni Fu, Xiaoqiu Zhu, Jin Li, Hui Xu, Jing Wen, Fei Wang and Mingyan Guo from Sun Yat-sen University, Guangdong, China, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China and University of Virginia, Charlottesville, VA, USA discuss how interscalene brachial plexus block combined with general anesthesia attenuates stress and inflammatory response in arthroscopic shoulder surgery.

In arthroscopic shoulder surgery, general anesthesia (GA) is the common method of anesthesia. Recently, the combined usage of interscalene brachial plexus block with general anesthesia (ISB/GA) was reported to have a lower incidence of adverse side effects than GA alone. However, to date, no study has compared stress and inflammatory responses between these two methods. Since stress and inflammatory responses are critical on intraoperative management and postoperative recovery, the authors of this study integrated the laboratory and clinical methods and compared the stress and inflammatory factors, such as epinephrine, norepinephrine, glucose, lactate, inflammatory factors tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), as well as the clinical outcomes to determine whether ISB/GA provides an advantage on stress and inflammatory inhibition.

Data showed that ISB/GA resulted in significantly lower epinephrine, norepinephrine, and glucose levels perioperatively. Six hours after operation, the TNF-α and IL-6 levels were also significantly lower in the ISB/GA group. ISB/GA patients had lower blood pressure, a more stable heart rate, lower visual analog scale score, and less opioid consumption during and after surgery. The results indicate that ISB/GA is a better choice for arthroscopic shoulder surgery, owing to less stress and inflammatory responses during and after operation, which provides better clinical outcomes.