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Abstract The running of the top quark mass (m t) is probed at the next-to-next-to-leading order in quantum chromodynamics for the first time. The result is obtained by comparing calculations in the modified minimal subtraction ( $$\overline{{\text{MS}} }$$ ) renormalisation scheme to the CMS result on differential measurement of the top quark-antiquark ( $${\text{t}}\overline{{\text{t}} }$$ ) production cross section at $$\sqrt{s}$$ = 13 TeV. The scale dependence of m t is extracted as a function of the invariant mass of the $${\text{t}}\overline{{\text{t}} }$$ system, up to an energy scale of about 0.5 TeV. The observed running is found to be in good agreement with the three-loop solution of the renormalisation group equations on quantum chromodynamics.

Abstract We conduct a large (N = 6567) online experiment to measure the features of non-pharmaceutical interventions (NPIs) that citizens of six European countries perceive to lower the risk of transmission of SARS-Cov-2 the most. We collected data in Bulgaria (n = 1069), France (n = 1108), Poland (n = 1104), Italy (n = 1087), Spain (n = 1102) and Sweden (n = 1097). Based on the features of the most widely adopted public health guidelines to reduce SARS-Cov-2 transmission (mask wearing vs not, outdoor vs indoor contact, short vs 90 min meetings, few vs many people present, and physical distancing of 1 or 2 m), we conducted a discrete choice experiment (DCE) to estimate the public’s perceived risk of SARS-CoV-2 transmission in scenarios that presented mutually exclusive constellations of these features. Our findings indicate that participants’ perception of transmission risk was most influenced by the NPI attributes of mask-wearing and outdoor meetings and the least by NPI attributes that focus on physical distancing, meeting duration, and meeting size. Differentiating by country, gender, age, cognitive style (reflective or intuitive), and perceived freight of COVID-19 moreover allowed us to identify important differences between subgroups. Our findings highlight the importance of improving health policy communication and citizens’ health literacy about the design of NPIs and the transmission risk of SARS-Cov-2 and potentially future viruses.

IntroductionThe differential expression of emotional reactivity from early to late adulthood may involve maturation of prefrontal cortical responses to negative valence stimuli. In mice, age-related changes in affective behaviors have been reported, but the functional neural circuitry warrants further investigation.MethodsWe assessed age variations in affective behaviors and functional connectivity in male and female C57BL6/J mice. Mice aged 10, 30 and 60 weeks (wo) were tested over 8 weeks for open field activity, sucrose preference, social interactions, fear conditioning, and functional neuroimaging. Prefrontal cortical and hippocampal tissues were excised for metabolomics.ResultsOur results indicate that young and old mice differ significantly in affective behavioral, functional connectome and prefrontal cortical-hippocampal metabolome. Young mice show a greater responsivity to novel environmental and social stimuli compared to older mice. Conversely, late middle-aged mice (60wo group) display variable patterns of fear conditioning and during re-testing in a modified context. Functional connectivity between a temporal cortical/auditory cortex network and subregions of the anterior cingulate cortex and ventral hippocampus, and a greater network modularity and assortative mixing of nodes was stronger in young versus older adult mice. Metabolome analyses identified differences in several essential amino acids between 10wo mice and the other age groups.DiscussionThe results support differential expression of ‘emotionality’ across distinct stages of the mouse lifespan involving greater prefrontal-hippocampal connectivity and neurochemistry.

Abstract Risk tolerance decreases from Monday to Thursday and increases on Friday. Antecedents of this weekly risk cycle are difficult to investigate experimentally as manipulating the seven-day cycle is impractical. Here we used temporal disorientation during the UK COVID-19 lockdown to conduct a natural experiment. In two studies, we measured responses to risk in participants with either a strong or weak sense of weekday, after either a short or long period of disruption to their weekly routine by lockdown. In Study 1 (N = 864), the weekly risk cycle was consistent in risk attitude measures specifically to participants who reported a strong sense of weekday. In Study 2 (N = 829), the weekly risk cycle was abolished, even for participants who retained a strong sense of weekday. We propose that two factors sustain the weekly risk cycle. If the sense of weekday is lacking, then weekday will have little effect because the current day is not salient. If weekday associations decay, then weekday will have little effect because the current day is not meaningful. The weekly risk cycle is strong and consistent when (i) sense of weekday is robust and (ii) weekday associations are maintained.

This research aimed to develop a low-saturated ingredient as substitute of saturated fats by structuring lipids through a simple enzymatic glycerolysis process. To this purpose, peanut oil (10 g) was mixed with glycerol (1:1 molar ratio) and lipase (0.4 g). The glycerolysis reaction was carried out for 16 h at 65°C under constant stirring. The obtained structured lipid was then used as a fat source in a mixture for the production of ice cream. The mixtures obtained with structured and unstructured peanut oil were compared to a classical cream-based mixture in terms of particle size and ?-potential. Afterward, the obtained ice creams were assessed based on their physical properties during melting and textural attributes. Glycerolysis of peanut oil reduced the particle size of the formed mixtures, which later created ice creams with a slower melting rate (0.044 g·min-1) compared to the peanut oil-based formulation (0.77 g·min-1). Similar dripping times were measured for the structured-lipid (60.33 ± 1.2 min) and the cream-based (65.00 ± 1.6 min) ice creams. Moreover, the firmness and consistency of the ice cream made with the structured lipid were not significantly different (p < 0.05) compared to the traditional cream-based product. Overall, the results of the present study clearly indicated that structured lipids could be used as ingredient in ice cream production, paving the way for a partial replacement of saturated fats in food formulations.

Abstract Background Several findings suggest neuroinflammation as a contributing factor for the onset of psychiatric disorders such as Alzheimer’s disease, depression, and anxiety. There is increasing evidence pointing out that the Mediterranean diet influences brain and behavior. Mediterranean herbs and spices have been shown to be within those components of the Mediterranean diet involved in cognitive enhancement. Thus, we investigated the influence of Mediterranean natural extracts (MNE), Rosemary extract (RE) and Glycyrrhiza glabra root extract (GGRE), on cognitive behavior. Results Adult zebrafish were exposed to RE or GGRE (100 and 250 mg/L) treatments. Both MNE improved memory retention during the T-maze test, although no improvements were observed during the novel object preference. Similarly, chronic administration of RE (150 mg/Kg) and GGRE (150 mg/Kg) improved, respectively, spatial and retention memory, as assessed by the Morris Water Maze (MWM), and the Elevated Plus Maze (EPM) in healthy male rats. However, no improvements were observed during the novel object recognition. Finally, male, and female rats were chronically treated with lipopolysaccharide [(LPS) 300 ug/kg] and orally administered with RE. Interestingly, RE reversed LPS-induced cognitive deficit during the MWM and EPM in female rats. Conclusions We found that MNE improved cognition in both zebrafish and rats. Moreover, MNE rescued LPS-induced cognitive impairment in a gender-specific manner. Therefore, our study supports the view that zebrafish represent a valuable preclinical model for drug discovery in neuroscience. These findings contribute to an exciting and growing body of research suggesting that MNE may play an important role in the prevention of cognitive impairment.

ABSTRACT Within epithelial cells, Pseudomonas aeruginosa depends on its type III secretion system (T3SS) to escape vacuoles and replicate rapidly in the cytosol. Previously, it was assumed that intracellular subpopulations remaining T3SS-negative (and therefore in vacuoles) were destined for degradation in lysosomes, supported by data showing vacuole acidification. Here, we report in both corneal and bronchial human epithelial cells that vacuole-associated bacteria can persist, sometimes in the same cells as cytosolic bacteria. Using a combination of phase-contrast, confocal, and correlative light-electron microscopy (CLEM), we also found they can demonstrate biofilm-associated markers: cdrA and cyclic-di-GMP (c-di-GMP). Vacuolar-associated bacteria, but not their cytosolic counterparts, tolerated the cell-permeable antibiotic ofloxacin. Surprisingly, use of mutants showed that both persistence in vacuoles and ofloxacin tolerance were independent of the biofilm-associated protein CdrA or exopolysaccharides (Psl, Pel, alginate). A T3SS mutant (ΔexsA) unable to escape vacuoles phenocopied vacuole-associated subpopulations in wild-type PAO1-infected cells, with results revealing that epithelial cell death depended upon bacterial viability. Intravital confocal imaging of infected mouse corneas confirmed that P. aeruginosa formed similar intracellular subpopulations within epithelial cells in vivo. Together, these results show that P. aeruginosa differs from other pathogens by diversifying intracellularly into vacuolar and cytosolic subpopulations that both contribute to pathogenesis. Their different gene expression and behavior (e.g., rapid replication versus slow replication/persistence) suggest cooperation favoring both short- and long-term interests and another potential pathway to treatment failure. How this intracellular diversification relates to previously described “acute versus chronic” virulence gene-expression phenotypes of P. aeruginosa remains to be determined. IMPORTANCE Pseudomonas aeruginosa can cause sight- and life-threatening opportunistic infections, and its evolving antibiotic resistance is a growing concern. Most P. aeruginosa strains can invade host cells, presenting a challenge to therapies that do not penetrate host cell membranes. Previously, we showed that the P. aeruginosa type III secretion system (T3SS) plays a pivotal role in survival within epithelial cells, allowing escape from vacuoles, rapid replication in the cytoplasm, and suppression of host cell death. Here, we report the discovery of a novel T3SS-negative subpopulation of intracellular P. aeruginosa within epithelial cells that persist in vacuoles rather than the cytoplasm and that tolerate a cell-permeable antibiotic (ofloxacin) that is able to kill cytosolic bacteria. Classical biofilm-associated markers, although demonstrated by this subpopulation, are not required for vacuolar persistence or antibiotic tolerance. These findings advance our understanding of how P. aeruginosa hijacks host cells, showing that it diversifies into multiple populations with T3SS-negative members enabling persistence while rapid replication is accomplished by more vulnerable T3SS-positive siblings. Intracellular P. aeruginosa persisting and tolerating antibiotics independently of the T3SS or biofilm-associated factors could present additional challenges to development of more effective therapeutics.

Osteosarcoma is a high-grade sarcoma characterized by osteoid formation, nearly universal expression of IGF1R and with a subset expressing HER-2. These qualities provide opportunities for the use of the alpha particle-emitting isotopes to provide targeted radiation therapy via alpha particles precisely to bone-forming tumors in addition to IFG1R or Her-2 expressing metastases. This review will detail experience using the alpha emitter radium-223 (223Ra, tradename Xofigo), that targets bone formation, in osteosarcoma, specifically related to patient selection, use of gemcitabine for radio-sensitization, and using denosumab to increasing the osteoblastic phenotype of these cancers. A case of an inoperable left upper lobe vertebral-paraspinal-mediastinal osteoblastic lesion treated successfully with 223Ra combined with gemcitabine is described. Because not all areas of osteosarcoma lesions are osteoblastic, but nearly all osteosarcoma cells overexpress IGF1R, and some subsets expressing Her-2, the anti-IGF1R antibody FPI-1434 linked to actinium-225 (225Ac) or the Her-2 antibody linked to thorium-227 (227Th) may become other means to provide targeted alpha particle therapy against osteosarcoma (NCT03746431 and NCT04147819).

Cognitive alterations are a common feature associated with many neurodegenerative diseases and are considered a major health concern worldwide. Cognitive alterations are triggered by microglia activation and oxidative/inflammatory processes in specific areas of the central nervous system. Consumption of bioactive compounds with antioxidative and anti-inflammatory effects, such as astaxanthin and spirulina, can help in preventing the development of these pathologies. In this study, we have investigated the potential beneficial neuroprotective effects of a low dose of astaxanthin (ASX) microencapsulated within spirulina (ASXSP) in female rats to prevent the cognitive deficits associated with the administration of LPS. Alterations in memory processing were evaluated in the Y-Maze and Morris Water Maze (MWM) paradigms. Changes in microglia activation and in gut microbiota content were also investigated. Our results demonstrate that LPS modified long-term memory in the MWM and increased microglia activation in the hippocampus and prefrontal cortex. Preventive treatment with ASXSP ameliorated LPS-cognitive alterations and microglia activation in both brain regions. Moreover, ASXSP was able to partially revert LPS-induced gut dysbiosis. Our results demonstrate the neuroprotective benefits of ASX when microencapsulated with spirulina acting through different mechanisms, including antioxidant, anti-inflammatory and, probably, prebiotic actions.

The discrimination of tumor-infiltrated tissue from non-tumorous brain tissue during neurosurgical tumor excision is a major challenge in neurosurgery. It is critical to achieve full tumor removal since it directly correlates with the survival rate of the patient. Optical coherence tomography (OCT) might be an additional imaging method in the field of neurosurgery that enables the classification of different levels of tumor infiltration and non-tumorous tissue. This work investigated two OCT systems with different imaging wavelengths (930 nm/1310 nm) and different resolutions (axial (air): 4.9 μm/16 μm, lateral: 5.2 μm/22 μm) in their ability to identify different levels of tumor infiltration based on freshly excised ex vivo brain samples. A convolutional neural network was used for the classification. For both systems, the neural network could achieve classification accuracies above 91% for discriminating between healthy white matter and highly tumor infiltrated white matter (tumor infiltration >60%) .This work shows that both OCT systems with different optical properties achieve similar results regarding the identification of different stages of brain tumor infiltration.

Abstract Background Voluntary medical male circumcision (VMMC) is a key component of combination HIV-prevention programmes. Several high-HIV-prevalence countries in sub-Saharan Africa, including Zimbabwe, are looking to scale up VMMC activities. There is limited evidence on how a combination of social learning from peer education by a role model with different behavioural incentives influences demand for VMMC in such settings. Methods/Design This matched-cluster randomised controlled trial with 1740 participants will compare two behavioural incentives against a control with no intervention. In the intervention clusters, participants will participate in an education session delivered by a circumcised young male (“role model”) on the risks of HIV infection and the benefits from medical male circumcision. All participants will receive contributions towards transport costs to access medical male circumcision at participating clinics. Via blocked randomisation, in the intervention clusters participants will be randomly assigned to receive one of two types of incentives – fixed cash payment or lottery payment – both conditional on undergoing surgical VMMC. In two sites, a community-led intervention will also be implemented to address social obstacles and to increase support from peers, families and social structures. Baseline measures of endpoints will be gathered in surveys. Follow-up assessment at 6 months will include self-reported uptake of VMMC triangulated with clinic data. Discussion This is the first trial to pilot-test social learning to improve risk perception and self-efficacy and to address the fear of pain associated with VMMC and possible present-biased preferences with front-loaded compensations as well as fixed or lottery-based cash payments. This study will generate important knowledge to inform HIV-prevention policies about the effectiveness of behavioural interventions and incentives, which could be easily scaled-up. Trial registration This trial has been registered on ClinicalTrials.gov (identifier: NCT03565588). Registered on 21 June 2018.

In late 2019, COVID-19 emerged in Wuhan, China. Currently, it is an ongoing global health threat stressing the need for therapeutic compounds. Linking the virus life cycle and its interaction with cell receptors and internal cellular machinery is key to developing therapies based on the control of infectivity and inflammation. In this framework, we evaluate the combination of cannabidiol (CBD), as an anti-inflammatory molecule, and terpenes, by their anti-microbiological properties, in reducing SARS-CoV-2 infectivity. Our group settled six formulations combining CBD and terpenes purified from Cannabis sativa L, Origanum vulgare, and Thymus mastichina. The formulations were analyzed by HPLC and GC-MS and evaluated for virucide and antiviral potential by in vitro studies in alveolar basal epithelial, colon, kidney, and keratinocyte human cell lines.Conclusions and ImpactWe demonstrate the virucide effectiveness of CBD and terpene-based formulations. F2TC reduces the infectivity by 17%, 24%, and 99% for CaCo-2, HaCat, and A549, respectively, and F1TC by 43%, 37%, and 29% for Hek293T, HaCaT, and Caco-2, respectively. To the best of our knowledge, this is the first approach that tackles the combination of CBD with a specific group of terpenes against SARS-CoV-2 in different cell lines. The differential effectiveness of formulations according to the cell line can be relevant to understanding the pattern of virus infectivity and the host inflammation response, and lead to new therapeutic strategies.

Abstract Background HIV incidence in adolescent girls and young women remains high in sub-Saharan Africa. Progress towards uptake of HIV prevention methods remains low. Studies of oral pre-exposure prophylaxis (PrEP) have shown that uptake and adherence may be low due to low-risk perception and ambivalence around using antiretrovirals for prevention. No evidence exists on whether an interactive intervention aimed at adjusting risk perception and addressing the uncertainty around PrEP will improve uptake. This pilot research trial aims to provide an initial evaluation of the impact of an interactive digital tablet-based counselling session, correcting risk perception, and addressing ambiguity around availability, usability, and effectiveness of PrEP. Methods/Design This is a matched-cluster randomized controlled trial which will compare an interactive tablet-based education intervention against a control with no intervention. The study will be implemented in eight sites. In each site, two matched clusters of villages will be created. One cluster will be randomly allocated to intervention. In two sites, a community engagement intervention will also be implemented to address social obstacles and to increase support from peers, families, and social structures. A total of 1200 HIV-negative young women aged 18–24 years, not on PrEP at baseline, will be eligible. Baseline measures of endpoints will be gathered in surveys. Follow-up assessment at six months will include biomarkers of PrEP uptake and surveys. Discussion This will be the first randomized controlled trial to determine whether interactive feedback counselling leads to uptake of HIV prevention methods such as PrEP and reduces risky sexual behavior. If successful, policymakers could consider such an intervention in school-based education campaigns or as post-HIV-testing counselling for young people. Trial registration Clinicaltrials.gov, NCT03565575. Registered on 21 June 2018.

Summary: Monoamine neurotransmitters are released by specialized neurons regulating behavioral, motor, and cognitive functions. Although the localization of monoaminergic neurons in the brain is well known, the distribution and kinetics of monoamines remain unclear. Here, we generated a murine brain atlas of serotonin (5-HT), dopamine (DA), and norepinephrine (NE) levels using mass spectrometry imaging (MSI). We found several nuclei rich in both 5-HT and a catecholamine (DA or NE) and identified the paraventricular nucleus of the thalamus (PVT), where 5-HT and NE are co-localized. The analysis of 5-HT fluctuations in response to acute tryptophan depletion and infusion of isotope-labeled tryptophan in vivo revealed a close kinetic association between the raphe nuclei, PVT, and amygdala but not the other nuclei. Our findings imply the existence of a highly dynamic 5-HT-mediated raphe to PVT pathway that likely plays a role in the brain monoamine system. : Spectroscopy; Neuroscience; Systems Neuroscience Subject Areas: Spectroscopy, Neuroscience, Systems Neuroscience

In two pre-registered online studies during the COVID-19 pandemic and the early 2020 lockdown (one of which with a UK representative sample) we elicit risk-tolerance for 1,254 UK residents using four of the most widely applied risk-taking tasks in behavioral economics and psychology. Specifically, participants completed the incentive-compatible Balloon Analog Risk Task (BART) and the Binswanger-Eckel-Grossman (BEG) multiple lotteries task, as well as the Domain-Specific Risk-Taking Task (DOSPERT) and the self-reported questions for risk-taking used in the German Socio-economic Panel (SOEP) study. In addition, participants in the UK representative sample answered a range of questions about COVID-19-related risky behaviors selected from the UCL COVID-19 Social Survey and the ICL-YouGov survey on COVID-19 behaviors. Consistently with pre-COVID-19 times, we find that risk tolerance during the UK lockdown (i) was higher in men than in women and (ii) decreased with age. Undocumented in pre-COVID-19 times, we find some evidence for healthier participants displaying significantly higher risk-tolerance for self-reported risk measures. We find no systematic nor robust patterns of association between the COVID-19 risky behaviors and the four risk-taking tasks in our study. Moreover, we find no evidence in support of the so-called “risk compensation” hypothesis. If anything, it appears that participants who took greater risk in real-life COVID-19-relevant risky behaviors (e.g., isolating or taking precautions) also exhibited higher risk-tolerance in our experimental and self-reported risk-taking measures.

Background: The human gut microbiota has emerged as a key factor in the development of obesity. Certain probiotic strains have shown anti-obesity effects. The objective of this study was to investigate whether Bifidobacterium longum APC1472 has anti-obesity effects in high-fat diet (HFD)-induced obese mice and whether B. longum APC1472 supplementation reduces body-mass index (BMI) in healthy overweight/obese individuals as the primary outcome. B. longum APC1472 effects on waist-to-hip ratio (W/H ratio) and on obesity-associated plasma biomarkers were analysed as secondary outcomes. Methods: B. longum APC1472 was administered to HFD-fed C57BL/6 mice in drinking water for 16 weeks. In the human intervention trial, participants received B. longum APC1472 or placebo supplementation for 12 weeks, during which primary and secondary outcomes were measured at the beginning and end of the intervention. Findings: B. longum APC1472 supplementation was associated with decreased bodyweight, fat depots accumulation and increased glucose tolerance in HFD-fed mice. While, in healthy overweight/obese adults, the supplementation of B. longum APC1472 strain did not change primary outcomes of BMI (0.03, 95% CI [-0.4, 0.3]) or W/H ratio (0.003, 95% CI [-0.01, 0.01]), a positive effect on the secondary outcome of fasting blood glucose levels was found (-0.299, 95% CI [-0.44, -0.09]). Interpretation: This study shows a positive translational effect of B. longum APC1472 on fasting blood glucose from a preclinical mouse model of obesity to a human intervention study in otherwise healthy overweight and obese individuals. This highlights the promising potential of B. longum APC1472 to be developed as a valuable supplement in reducing specific markers of obesity. Funding: This research was funded in part by Science Foundation Ireland in the form of a Research Centre grant (SFI/12/RC/2273) to APC Microbiome Ireland and by a research grant from Cremo S.A.

We propose an implementation of a two-dimensional Z_{2} lattice gauge theory model on a shallow quantum circuit, involving a number of single- and two-qubit gates comparable to what can be achieved with present-day and near-future technologies. The ground-state preparation is numerically analyzed on a small lattice with a variational quantum algorithm, which requires a small number of parameters to reach high fidelities and can be efficiently scaled up on larger systems. Despite the reduced size of the lattice we consider, a transition between confined and deconfined regimes can be detected by measuring expectation values of Wilson loop operators or the topological entropy. Moreover, if periodic boundary conditions are implemented, the same optimal solution is transferable among all four different topological sectors, without any need for further optimization on the variational parameters. Our work shows that variational quantum algorithms provide a useful technique to be added in the growing toolbox for digital simulations of lattice gauge theories.

Nutrition is a crucial component for maintenance of brain function and mental health. Accumulating evidence suggests that certain molecular compounds derived from diet can exert neuroprotective effects against chronic stress, and moreover improve important neuronal processes vulnerable to the stress response, such as plasticity and neurogenesis. Phospholipids are naturally occurring amphipathic molecules with promising potential to promote brain health. However, it is unclear whether phospholipids are able to modulate neuronal function directly under a stress-related context. In this study, we investigate the neuroprotective effects of phosphatidylcholine (PC), lysophosphatidylcholine (LPC), phosphatidylserine (PS), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylglycerol (PG), phosphatidic acid (PA), sphingomyelin (SM) and cardiolipin (CL) against corticosterone (CORT)-induced cytotoxicity in primary cultured rat cortical neurons. In addition, we examine their capacity to modulate proliferation and differentiation of hippocampal neural progenitor cells (NPCs).We show that PS, PG and PE can reverse CORT-induced cytotoxicity and neuronal depletion in cortical cells. On the other hand, phospholipid exposure was unable to prevent the decrease of Bdnf expression produced by CORT. Interestingly, PS was able to increase hippocampal NPCs neurosphere size, and PE elicited a significant increase in astrocytic differentiation in hippocampal NPCs. Together, these results indicate that specific phospholipids protect cortical cells against CORT-induced cytotoxicity and improve proliferation and astrocytic differentiation in hippocampal NPCs, suggesting potential implications on neurodevelopmental and neuroprotective pathways relevant for stress-related disorders.

À l’aube de l’Unité d’Italie le choix d’écrire des poèmes sur le vin répond à de nouvelles motivations par rapport au siècles précedents. Le vin en vers peut aborder le discours politique nationaliste, le discours social sur l’égalité et les droits de l’homme, le discours économique lié à la production vinicole, les polémiques littéraires, l’anticléricalisme. Entre poésie, politique et oenologie cet article présente les différentes facettes de cette innovation thématique. Keywords : vin, oenologie, politique, poésie, Italie post-unitaire

Background: Neurosurgical task shifting and task sharing (TS/S), delegating clinical care to non-neurosurgeons, is ongoing in many hospital systems in which neurosurgeons are scarce. Although TS/S can increase access to treatment, it remains highly controversial. This survey investigated perceptions of neurosurgical TS/S to elucidate whether it is a permissible temporary solution to the global workforce deficit. Methods: The survey was distributed to a convenience sample of individuals providing neurosurgical care. A digital survey link was distributed through electronic mailing lists of continental neurosurgical societies and various collectives, conference announcements, and social media platforms (July 2018–January 2019). Data were analyzed by descriptive statistics and univariate regression of Likert Scale scores. Results: Survey respondents represented 105 of 194 World Health Organization member countries (54.1%; 391 respondents, 162 from high-income countries and 229 from low- and middle-income countries [LMICs]). The most agreed on statement was that task sharing is preferred to task shifting. There was broad consensus that both task shifting and task sharing should require competency-based evaluation, standardized training endorsed by governing organizations, and maintenance of certification. When perspectives were stratified by income class, LMICs were significantly more likely to agree that task shifting is professionally disruptive to traditional training, task sharing should be a priority where human resources are scarce, and to call for additional TS/S regulation, such as certification and formal consultation with a neurosurgeon (in person or electronic/telemedicine). Conclusions: Both LMIC and high-income countries agreed that task sharing should be prioritized over task shifting and that additional recommendations and regulations could enhance care. These data invite future discussions on policy and training programs. Key words: Global health, Global neurosurgery, LMIC, Neurotrauma, Task sharing, Task shifting, Workforce

Using a nationally representative sample of 1052 respondents from the United Kingdom, we systematically tested the associations between the experimental trust game and a range of popular self-reported measures for trust, such as the General Social Survey (GSS) and the Rosenberg scale for self-reported trust. We find that, in our UK representative sample, the experimental trust game significantly and positively predicts generalised self-reported trust in the GSS. This association is robust across a number of alternative empirical specifications, which account for multiple hypotheses corrections and control for other social preferences as measured by the dictator game and the public good game, as well as for a broad range of individual characteristics, such as gender, age, education, and personal income. We discuss how these results generalise to nationally representative samples from six other Organisation for Economic Co-operation and Development (OECD) countries (France, Germany, Italy, Korea, Slovenia, and the US).

Honey is a natural sweetener and its quality labels are associated to its botanical or geographical origin, which is being established by palynological and sensorial analysis. The use of fast and non-invasive techniques such as an electronic nose can become an alternative for honey classification. In this study, the operational parameters of a commercial electronic nose were validated to determine the honey odor profile. A central composite design with five factors, three levels and 28 assays was used, varying sample amounts (1, 2 and 3 g), incubation temperature (30, 40 and 50 °C), incubation time 30 min), gas flow (50, 150 and 250 mL/min) and injection time (100, 200 and 300 s). The commercial nose had ten sensors. Repeatability was evaluated with a coefficient of variation of 10 %. The response surface methodology was used and the optimal operating conditions were: 3 g of sample, incubation at 50 °C for 17 min, gas flow of 100 mL/min and sampling time of 150 s. Finally, these parameters were used to analyze 19 samples of honey, which were classified according to their odor profiles, showing that it can be a useful tool to classify honey.

ABSTRACT Pseudomonas aeruginosa is among bacterial pathogens capable of twitching motility, a form of surface-associated movement dependent on type IV pili (T4P). Previously, we showed that T4P and twitching were required for P. aeruginosa to cause disease in a murine model of corneal infection, to traverse human corneal epithelial multilayers, and to efficiently exit invaded epithelial cells. Here, we used live wide-field fluorescent imaging combined with quantitative image analysis to explore how twitching contributes to epithelial cell egress. Results using time-lapse imaging of cells infected with wild-type PAO1 showed that cytoplasmic bacteria slowly disseminated throughout the cytosol at a median speed of >0.05 μm s−1 while dividing intracellularly. Similar results were obtained with flagellin (fliC) and flagellum assembly (flhA) mutants, thereby excluding swimming, swarming, and sliding as mechanisms. In contrast, pilA mutants (lacking T4P) and pilT mutants (twitching motility defective) appeared stationary and accumulated in expanding aggregates during intracellular division. Transmission electron microscopy confirmed that these mutants were not trapped within membrane-bound cytosolic compartments. For the wild type, dissemination in the cytosol was not prevented by the depolymerization of actin filaments using latrunculin A and/or the disruption of microtubules using nocodazole. Together, these findings illustrate a novel form of intracellular bacterial motility differing from previously described mechanisms in being directly driven by bacterial motility appendages (T4P) and not depending on polymerized host actin or microtubules. IMPORTANCE Host cell invasion can contribute to disease pathogenesis by the opportunistic pathogen Pseudomonas aeruginosa. Previously, we showed that the type III secretion system (T3SS) of invasive P. aeruginosa strains modulates cell entry and subsequent escape from vacuolar trafficking to host lysosomes. However, we also showed that mutants lacking either type IV pili (T4P) or T4P-dependent twitching motility (i) were defective in traversing cell multilayers, (ii) caused less pathology in vivo, and (iii) had a reduced capacity to exit invaded cells. Here, we report that after vacuolar escape, intracellular P. aeruginosa can use T4P-dependent twitching motility to disseminate throughout the host cell cytoplasm. We further show that this strategy for intracellular dissemination does not depend on flagellin and resists both host actin and host microtubule disruption. This differs from mechanisms used by previously studied pathogens that utilize either host actin or microtubules for intracellular dissemination independently of microbe motility appendages.

Behavioral spillovers refer to the influence that a given intervention targeting behavior 1 exerts on a subsequent, non-targeted, behavior 2, which may or may not be in the same domain (health, finance, etc.) as one another. So, a nudge to exercise more, for example, could lead people to eat more or less, or possibly even to give more or less to charity depending on the nature of the spillover. But what if spillovers also operate backward; that is, if the expectation of behavior 1 influences behavior 0 that precedes it? For example, a person may form an intention to exercise prompted by a policy intervention but overeat at present as a result. We define such a possibility as a “spillunder.” In the proposed article, we critically review the few papers that we have identified through a narrative literature review which have demonstrated spillunder effects to date, and we propose a conceptual framework. Based on evidence about the human mind and behavior from psychology and economics, we argue that spillunder effects may be more common than the limited empirical findings suggest. We propose six representative mechanisms through which the prospect of behavior 1 may impact behavior 0: executive functions, moral licensing and moral cleansing, emotion regulation, energization, construal level, and savoring and dread. We further discuss the policy and practical implications of spillunder effects and examine methodological issues that need to be considered when empirically testing these effects. As with our earlier paper on spillovers, we aim to motivate other behavioral scientists to research behavioral spillunders more systematically and extensively, and to prompt decision makers to consider these effects when designing behavioral interventions.

A growing stream of literature at the interface between economics and psychology is currently investigating ‘behavioral spillovers’ in (and across) different domains, including health, environmental, and pro-social behaviors. A variety of empirical methods have been used to measure behavioral spillovers to date, from qualitative self-reports to statistical/econometric analyses, from online and lab experiments to field experiments. The aim of this paper is to critically review the main experimental and non-experimental methods to measure behavioral spillovers to date, and to discuss their methodological strengths and weaknesses. A consensus mixed-method approach is then discussed which uses between-subjects randomization and behavioral observations together with qualitative self-reports in a longitudinal design in order to follow up subjects over time. In particular, participants to an experiment are randomly assigned to a treatment group where a behavioral intervention takes place to target behavior 1, or to a control group where behavior 1 takes place absent any behavioral intervention. A behavioral spillover is empirically identified as the effect of the behavioral intervention in the treatment group on a subsequent, not targeted, behavior 2, compared to the corresponding change in behavior 2 in the control group. Unexpected spillovers and additional insights (e.g., drivers, barriers, mechanisms) are elicited through analysis of qualitative data. In the spirit of the pre-analysis plan, a systematic checklist is finally proposed to guide researchers and policy-makers through the main stages and features of the study design in order to rigorously test and identify behavioral spillovers, and to favor transparency, replicability, and meta-analysis of studies.

The essay offers a new understanding of Henry Charles Carey’s (1793–1879) social science. As one of the major intellectuals of the antebellum period that actively participated in the Republican Party, Carey’s works marked a reinterpretation of US nationalism in which the State became the guarantee of the exceptional American social order against social conflict and economic crisis following the capitalistic transition. Protectionism was conceived as a political measure to defend the harmony of the nation’s interests. His social science should be understood as an attempt to scientifically re-legitimize the order: as a social science of the American nation.

We propose a reinforcement learning (RL) scheme for feedback quantum control within the quantum approximate optimization algorithm (QAOA). We reformulate the QAOA variational minimization as a learning task, where an RL agent chooses the control parameters for the unitaries, given partial information on the system. Such an RL scheme finds a policy converging to the optimal adiabatic solution of the quantum Ising chain that can also be successfully transferred between systems with different sizes, even in the presence of disorder. This allows for immediate experimental verification of our proposal on more complicated models: the RL agent is trained on a small control system, simulated on classical hardware, and then tested on a larger physical sample.

Qua e là, nell’imponente opera letteraria e saggistica, Carducci ci parla della sua infanzia tra Versilia e Maremma toscana, attribuendo a brevi ricordi, a volte ricorrenti, funzioni che vanno ben al di là della mera cronaca autobiografica. Essi concorrono infatti alla costruzione del personaggio pubblico, del poeta come dell’intellettuale, e alla creazione di un mito identitario maremmano. Il presente articolo analizza alcuni di questi ricordi d’infanzia, iniziando da quelli in prosa e passando poi a quelli in versi.

Microbial communities are important for the health of mucosal tissues. Traditional culture and gene sequencing have demonstrated bacterial populations on the conjunctiva. However, it remains unclear if the cornea, a transparent tissue critical for vision, also hosts a microbiome. Corneas of wild-type, IL-1R (-/-) and MyD88 (-/-) C57BL/6 mice were imaged after labeling with alkyne-functionalized D-alanine (alkDala), a probe that only incorporates into the peptidoglycan of metabolically active bacteria. Fluorescence in situ hybridization (FISH) was also used to detect viable bacteria. AlkDala labeling was rarely observed on healthy corneas. In contrast, adjacent conjunctivae harbored filamentous alkDala-positive forms, that also labeled with DMN-Tre, a Corynebacterineae-specific probe. FISH confirmed the absence of viable bacteria on healthy corneas, which also cleared deliberately inoculated bacteria within 24 h. Differing from wild-type, both IL-1R (-/-) and MyD88 (-/-) corneas harbored numerous alkDala-labeled bacteria, a result abrogated by topical antibiotics. IL-1R (-/-) corneas were impermeable to fluorescein suggesting that bacterial colonization did not reflect decreased epithelial integrity. Thus, in contrast to the conjunctiva and other mucosal surfaces, healthy murine corneas host very few viable bacteria, and this constitutive state requires the IL-1R and MyD88. While this study cannot exclude the presence of fungi, viruses, or non-viable or dormant bacteria, the data suggest that healthy murine corneas do not host a resident viable bacterial community, or microbiome, the absence of which could have important implications for understanding the homeostasis of this tissue.

Abstract

We address the second-harmonic generation process in a quantum frame. Starting with a perturbative approach, we show that it is possible to achieve a number of analytic results, ranging from the up-conversion probability to the statistical properties of the generated light. In particular, the moments and the correlations of the photon-number distribution of the second-harmonic light generated by any initial state are retrieved. When possible, a comparison with the results achieved with the classical regime is successfully provided. The nonclassicality of some benchmark states is investigated by inspecting the corresponding autocorrelation function.

A new heteroarylene-vinylene donor-acceptor low bandgap polymer, the poly(DEHT-V-BTD), containing vinylene-spaced efficient donor (dialkoxythiophene) and acceptor (benzothiadiazole) moieties, is presented. Electropolymerization has been carried out by several electrochemical techniques and the results are compared. In particular, the pulsed potentiostatic method was able to provide layers with sufficient amounts of material. Cyclic voltammetries showed reversible behavior towards both p- and n-doping. The HOMO, LUMO, and bandgap energies were estimated to be −5.3, −3.6 and 1.8 eV, respectively. In situ UV-Vis measurements have established that the presence of the vinylene group stabilizes the formation of polaronic charge carriers even at high doping levels.

A series of compounds, featuring an ethenylic bridge and quinoline and isoquinoline end capping units possessing systematically varied substitution patterns, were prepared as molecular materials for electrochromic applications. The different structures were optimized in order to maximize the electrochromic contrast in the visible region, mostly by achieving a completely UV-absorbing oxidized state. Density functional theory (DFT) calculations are exploited in order to rationalize the correlation between the molecular structure, the functional groups’ electronic properties, and the electrochemical behavior. It is shown that the molecular planarity (i.e. ring/ring π conjugation) plays a major role in defining the mechanism of the electrochemical charge transfer reaction, while the substituent’s nature has an influence on the LUMO energy. Among the compounds here studied, the (E)-10-methyl-9-(2-(2-methylisoquinolinium-1-yl)-vinyl)-1,2,3,4-tetrahydroacri-dinium trifluoromethanesulfonate derivative shows the most interesting properties as an electrochromophore.

ABSTRACT Group B Streptococcus (GBS), in the transition from commensal organisms to pathogens, will encounter diverse host environments and, thus, require coordinated control of the transcriptional responses to these changes. This work was aimed at better understanding the role of two-component signal transduction systems (TCS) in GBS pathophysiology through a systematic screening procedure. We first performed a complete inventory and sensory mechanism classification of all putative GBS TCS by genomic analysis. Five TCS were further investigated by the generation of knockout strains, and in vitro transcriptome analysis identified genes regulated by these systems, ranging from 0.1% to 3% of the genome. Interestingly, two sugar phosphotransferase systems appeared to be differentially regulated in the TCS-16 knockout strain (TCS loci were numbered in order of their appearance on the chromosome), suggesting an involvement in monitoring carbon source availability. High-throughput analysis of bacterial growth on different carbon sources showed that TCS-16 was necessary for the growth of GBS on fructose-6-phosphate. Additional transcriptional analysis provided further evidence for a stimulus-response circuit where extracellular fructose-6-phosphate leads to autoinduction of TCS-16, with concomitant dramatic upregulation of the adjacent operon, which encodes a phosphotransferase system. The TCS-16-deficient strain exhibited decreased persistence in a model of vaginal colonization. All mutant strains were also characterized in a murine model of systemic infection, and inactivation of TCS-17 (also known as RgfAC) resulted in hypervirulence. Our data suggest a role for the previously unknown TCS-16, here named FspSR, in bacterial fitness and carbon metabolism during host colonization, and the data also provide experimental evidence for TCS-17/RgfAC involvement in virulence. IMPORTANCE Two-component systems have been evolved by bacteria to detect environmental changes, and they play key roles in pathogenicity. A comprehensive analysis of TCS in GBS has not been performed previously. In this work, we classify 21 TCS and present evidence for the involvement of two specific TCS in GBS virulence and colonization in vivo. Although pinpointing specific TCS stimuli is notoriously difficult, we used a combination of techniques to identify two systems with different effects on GBS pathogenesis. For one of the systems, we propose that fructose-6-phosphate, a metabolite in glycolysis, is sufficient to induce a regulatory response involving a sugar transport system. Our catalogue and classification of TCS may guide further studies into the role of TCS in GBS pathogenicity and biology.