Midfrontal theta transcranial alternating current stimulation modulates behavioural adjustment after error execution

Cognitive control during conflict monitoring, error processing, and post-error adjustment appear to be associated with the occurrence of midfrontal theta (MFϴ). While this association is supported by correlational EEG studies, much less is known about the possible causal link between MFϴ and error and conflict processing. In the present study, we aimed to explore the role of band-specific effects in modulating the error system during a conflict resolution. In turn, we delivered transcranial alternating current stimulation (tACS) at different frequency bands (delta δ, theta θ, alpha α, beta β, gamma γ) and sham stimulation over the medial frontal cortex (MFC) in 36 healthy participants performing a modified version of the Flanker task. Task performance and reports about the sensations (e.g. visual flickering, cutaneous burning) induced by the different frequency bands, were also recorded. We found that online θ-tACS increased the response speed to congruent stimuli after error execution with respect to sham stimulation. Importantly, the accuracy following the errors did not decrease because of speed-accuracy trade off. Moreover, tACS evoked visual and somatosensory sensations were significantly stronger at α-tACS and β-tACS compared to other frequencies. Our findings suggest that theta activity plays a causative role in modulating behavioural adjustments during perceptual choices in a stimulus-response conflict task. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Lt

Function Allocation between Automation and Human Pilot for Airborne Separation Assurance

Maintaining safe separation between aircraft is a key determinant of the airspace capacity to handle air transportation. With the advent of satellite-based surveillance, aircraft equipped with the needed technologies are now capable of maintaining awareness of their location in the airspace and sharing it with their surrounding traffic. As a result, concepts and cockpit automation are emerging to enable delegating the responsibility of maintaining safe separation from traffic to the pilot; thus increasing the airspace capacity by alleviating the limitation of the current non-scalable centralized ground-based system. In this paper, an analysis of allocating separation assurance functions to the human pilot and cockpit automation is presented to support the design of these concepts and technologies. A task analysis was conducted with the help of Petri nets to identify the main separation assurance functions and their interactions. Each function was characterized by three behavior levels that may be needed to perform the task: skill, rule and knowledge based levels. Then recommendations are made for allocating each function to an automation scale based on their behavior level characterization and with the help of Subject matter experts

Definition and Demonstration of a Methodology for Validating Aircraft Trajectory Predictors

This paper presents a new methodology for validating an aircraft trajectory predictor, inspired by the lessons learned from a number of field trials, flight tests and simulation experiments for the development of trajectory-predictor-based automation. The methodology introduces new techniques and a new multi-staged approach to reduce the effort in identifying and resolving validation failures, avoiding the potentially large costs associated with failures during a single-stage, pass/fail approach. As a case study, the validation effort performed by the Federal Aviation Administration for its En Route Automation Modernization (ERAM) system is analyzed to illustrate the real-world applicability of this methodology. During this validation effort, ERAM initially failed to achieve six of its eight requirements associated with trajectory prediction and conflict probe. The ERAM validation issues have since been addressed, but to illustrate how the methodology could have benefited the FAA effort, additional techniques are presented that could have been used to resolve some of these issues. Using data from the ERAM validation effort, it is demonstrated that these new techniques could have identified trajectory prediction error sources that contributed to several of the unmet ERAM requirements

The Economic Benefit of Data-Communication Technology on the New York Metroplex Area

The aim of this paper is to estimate the economic benefit for the New York Metroplex area of the controller-to-pilot communication standard known as Data-Communication. RAMS simulation software was first used to evaluate the potential impact of the new technology on airport operations in the three airports of LaGuardia, Newark and John F. Kennedy. The new technology would allow for a greater number of operations and reduce the average hourly workload for air traffic controllers. We employ a two steps procedure. First, we estimate a benefit function per number of hourly operations. Second, using the empirical distribution of hourly operations and the benefit function found in step one, we compute the average daily benefit from the technology as the reduced cost from delays plus the net effect on controllers workload due to its implementation. The procedure is applied at each airport individually and to the metroplex area as a whole. Our estimates show that the introduction of Data-Comm would yield significant savings in the New York Metroplex area

Global transcriptome analysis of the heat shock response of Bifidobacterium longum

Bifidobacteria are natural inhabitants of the human gastrointestinal tract and have been widely used as functional foods in different products. During industrial processing, bacterial cells undergo several stresses that can limit large-scale production and stability of the final product. To better understand the stress-response mechanisms of bifidobacteria, microarrays were used to obtain a global transcriptome profile of Bifidobacterium longum NCC2705 exposed to a heat shock treatment at 50°C for 3, 7 and 12 min. Gene expression data highlighted a profound modification of gene expression, with 46% of the genes being altered. This analysis revealed a slow-down of Bi. longum general metabolic activity during stress with a simultaneous activation of the classical heat shock stimulon. Moreover, the expression of several genes with unknown function was highly induced under stress conditions. Three of these were conserved in other bacteria species where they were also previously shown to be induced by high temperature, suggesting their widespread role in the heat stress response. Finally, the implication of the trans-translation machinery in the response of Bi. longum cells to heat shock was suggested by the induction of the gene encoding the tmRNA-associated small protein B (SmpB) with concomitant high constitutive expression of the tmRNA gen

Assessment of Air Traffic Controller Acceptability of Aircrew Route Change Requests

NASA developed the traffic aware strategic aircrew requests concept for a cockpit automation that identifies route improvements and advises the aircrew to request the change from the air traffic controller. In order to increase the chance of air traffic control approval, the automation ensures that the route is clear of known traffic, weather, and airspace restrictions. Hence the technology is anticipated to provide benefits in areas such as flight efficiency, flight schedule compliance, passenger comfort, and pilot and controller workload. In support of a field trial of a prototype of the technology, observations were conducted at the Atlanta and Jacksonville air traffic control centers to identify the main factors that affect the acceptability of aircrew requests by air traffic controllers. Observers shadowed air traffic controllers as the test flight pilot made pre-scripted requests to invoke acceptability issues and then they interviewed voluntarily fifty controllers with experience ranging from one to thirty-five years. The most common reason for rejecting requests is conflicting with traffic followed by violating air traffic procedures, increasing sector workload, and conflicting with major arrival and departure flows and flow restrictions. Quantitative parameters such as the distance that a route should maintain from sector boundaries and special use airspace were identified and recommended for inclusion in the automation

Extracellular Vesicles and Epidermal Growth Factor Receptor Activation: Interplay of Drivers in Cancer Progression

Extracellular vesicles (EVs) are of great interest to study the cellular mechanisms of cancer development and to diagnose and monitor cancer progression. EVs are a highly heterogeneous population of cell derived particles, which include microvesicles (MVs) and exosomes (EXOs). EVs deliver intercellular messages transferring proteins, lipids, nucleic acids, and metabolites with implications for tumour progression, invasiveness, and metastasis. Epidermal Growth Factor Receptor (EGFR) is a major driver of cancer. Tumour cells with activated EGFR could produce EVs disseminating EGFR itself or its ligands. This review provides an overview of EVs (mainly EXOs and MVs) and their cargo, with a subsequent focus on their production and effects related to EGFR activation. In particular, in vitro studies performed in EGFR-dependent solid tumours and/or cell cultures will be explored, thus shedding light on the interplay between EGFR and EVs production in promoting cancer progression, metastases, and resistance to therapies. Finally, an overview of liquid biopsy approaches involving EGFR and EVs in the blood/plasma of EGFR-dependent tumour patients will also be discussed to evaluate their possible application as candidate biomarkers

Balancing efficacy and tolerability of first-line systemic therapies for advanced hepatocellular carcinoma: a network metanalysis

Background: Atezolizumab+Bevacizumab represents the current standard of care for first-line treatment of advanced HCC. However, direct comparison with other combination treatments including immune-checkpoint inhibitors(ICI)+tyrosine-kinase inhibitors(TKIs) are lacking. Objectives: This network meta-analysis(NMA) aims to indirectly compare the efficacy and the safety of first-line systemic therapies for unresectable-advanced HCC. Method:A literature search of MEDLINE, EMBASE and SCOPUS databases was conducted up to 31st October, 2022. Phase III randomized controlled trials(RCTs) testing TKIs, including Sorafenib and Lenvatinib, or ICIs reporting overall survival(OS) and progression-free survival(PFS) were included. Individual survival data were extracted from OS and PFS curves to calculate restricted mean survival time (RMST). A Bayesian NMA was performed to compare treatments in terms of efficacy(15- and 30-month OS, 6-month PFS) and safety, represented by grade≥3(severe)adverse events(SAEs). The incremental safety-effectiveness ratio(ISER) as measure of net health benefit was calculated as the difference in SAEs probability divided by survival difference between the 2 most effective treatments. Results:Nine RCTs enrolling 6600 patients were included. Atezolizumab plus bevacizumab showed the highest probability(88%)of achieving the 30-month OS landmark. Lenvatinib showed a probability of 86% of achieving best PFS outcomes. ICI monotherapies ranked as most tolerable. Atezolizumab plus Bevacizumab showed the best net health benefit for OS, compared to Durvalumab plus Tremelimumab. When evaluating the net health benefit for PFS, at a willingness-to-risk threshold of 10% of SAEs for life-month gained, Atezolizumab plus Bevacizumab was favored in 78% of cases, while at threshold of 30% of SAEs for life-month gained, Lenvatinib was favored in 76% of cases. Conclusions: Atezolizumab plus Bevacizumab is the best treatment in terms of net benefit and therefore it should be recommended as standard of care. Compared to Atezolizumab plus Bevacizumab, Lenvatinib monotherapy had the best net benefit for PFS when physicians and patients are available to accept a higher risk of toxicity

Respiratory symptoms in children living near busy roads and their relationship to vehicular traffic: results of an Italian multicenter study (SIDRIA 2)

BACKGROUND: Epidemiological studies have provided evidence that exposure to vehicular traffic increases the prevalence of respiratory symptoms and may exacerbate pre-existing asthma in children. Self-reported exposure to road traffic has been questioned as a reliable measurement of exposure to air pollutants. The aim of this study was to investigate whether there were specific effects of cars and trucks traffic on current asthma symptoms (i.e. wheezing) and cough or phlegm, and to examine the validity of self-reported traffic exposure. METHODS: The survey was conducted in 2002 in 12 centers in Northern, Center and Southern Italy, different in size, climate, latitude and level of urbanization. Standardized questionnaires filled in by parents were used to collect information on health outcomes and exposure to traffic among 33,632 6-7 and 13-14 years old children and adolescents. Three questions on traffic exposure were asked: the traffic in the zone of residence, the frequency of truck and of car traffic in the street of residence. The presence of a possible response bias for the self-reported traffic was evaluated using external validation (comparison with measurements of traffic flow in the city of Turin) and internal validations (matching by census block, in the cities of Turin, Milan and Rome). RESULTS: Overall traffic density was weakly associated with asthma symptoms but there was a stronger association with cough or phlegm (high traffic density OR = 1.24; 95% CI: 1.04, 1.49). Car and truck traffic were independently associated with cough or phlegm. The results of the external validation did not support the existence of a reporting bias for the observed associations, for all the self-reported traffic indicators examined. The internal validations showed that the observed association between traffic density in the zone of residence and respiratory symptoms did not appear to be explained by an over reporting of traffic by parents of symptomatic subjects. CONCLUSION: Children living in zones with intense traffic are at higher risk for respiratory effects. Since population characteristics are specific, the results of validation of studies on self-reported traffic exposure can not be generalized

Isozyme-Specific Ligands for O-acetylserine sulfhydrylase, a Novel Antibiotic Target

Conceived and designed the experiments: FS PC BC ES AM. Performed the experiments: FS RS ES PF SR. Analyzed the data: FS BC ES PF GEK PFC AM. Contributed reagents/materials/analysis tools: PC PB GC. Wrote the paper: FS GEK BC AM.The last step of cysteine biosynthesis in bacteria and plants is catalyzed by O-acetylserine sulfhydrylase. In bacteria, two isozymes, O-acetylserine sulfhydrylase-A and O-acetylserine sulfhydrylase-B, have been identified that share similar binding sites, although the respective specific functions are still debated. O-acetylserine sulfhydrylase plays a key role in the adaptation of bacteria to the host environment, in the defense mechanisms to oxidative stress and in antibiotic resistance. Because mammals synthesize cysteine from methionine and lack O-acetylserine sulfhydrylase, the enzyme is a potential target for antimicrobials. With this aim, we first identified potential inhibitors of the two isozymes via a ligand- and structure-based in silico screening of a subset of the ZINC library using FLAP. The binding affinities of the most promising candidates were measured in vitro on purified O-acetylserine sulfhydrylase-A and O-acetylserine sulfhydrylase-B from Salmonella typhimurium by a direct method that exploits the change in the cofactor fluorescence. Two molecules were identified with dissociation constants of 3.7 and 33 µM for O-acetylserine sulfhydrylase-A and O-acetylserine sulfhydrylase-B, respectively. Because GRID analysis of the two isoenzymes indicates the presence of a few common pharmacophoric features, cross binding titrations were carried out. It was found that the best binder for O-acetylserine sulfhydrylase-B exhibits a dissociation constant of 29 µM for O-acetylserine sulfhydrylase-A, thus displaying a limited selectivity, whereas the best binder for O-acetylserine sulfhydrylase-A exhibits a dissociation constant of 50 µM for O-acetylserine sulfhydrylase-B and is thus 8-fold selective towards the former isozyme. Therefore, isoform-specific and isoform-independent ligands allow to either selectively target the isozyme that predominantly supports bacteria during infection and long-term survival or to completely block bacterial cysteine biosynthesis.Yeshttp://www.plosone.org/static/editorial#pee