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We study a class of static spherically symmetric vacuum solutions in modified teleparallel gravity solving the field equations for a specific model Ansatz, requiring the torsion scalar T to be constant. We discuss the models falling in this class. After some general considerations, we provide and investigate local solutions in the form of black holes and traversable wormholes as well as configurations that can match the anomalous rotation curves of galaxies. [ABSTRACT FROM AUTHOR]

The development of lipid nanoparticle (LNP) based therapeutics for delivery of RNA has triggered the advance of new strategies for formulation, such as high throughput microfluidics for precise mixing of components into well-defined particles. In this study, we have characterised the structure of LNPs throughout the formulation process using in situ small angle x-ray scattering in the microfluidic chip, then by sampling in the subsequent dialysis process. The final formulation was investigated with small angle x-ray (SAXS) and neutron (SANS) scattering, dynamic light scattering (DLS) and cryo-TEM. The effect on structure was investigated for LNPs with a benchmark lipid composition and containing different cargos: calf thymus DNA (DNA) and two model mRNAs, polyadenylic acid (polyA) and polyuridylic acid (polyU). The LNP structure evolved during mixing in the microfluidic channel, however was only fully developed during the dialysis. The colloidal stability of the final formulation was affected by the type of incorporated nucleic acids (NAs) and decreased with the degree of base-pairing, as polyU induced extensive particle aggregation. The main NA LNP peak in the SAXS data for the final formulation were similar, with the repeat distance increasing from polyU

Background: There is growing recognition of the importance of sex and gender differences within falls literature, but the characterization of such literature is uncertain. The aim of this scoping review was to (1) map the nature and extent of falls literature examining sex or gender differences among older adults, and (2) identify gaps and opportunities for further research and practice. Methods: We used a scoping review methodology. Eligible studies included participants with a mean age of ≥60 years and study aims specifying falls and either sex or gender concepts. MEDLINE, Embase, CINAHL, Ageline, and Psychinfo databases were searched from inception to March 2, 2022. Records were screened and charted by six independent reviewers. Descriptive and narrative reports were generated. Results: A total of 15,266 records were screened and 74 studies were included. Most studies reported on sex and gender differences in fall risk factors (n = 52, 70%), incidence/prevalence (n = 26, 35%), fall consequences (n = 22, 30%), and fall characteristics (n = 15, 20%). The majority of studies (n = 70, 95%) found significant sex or gender differences in relation to falls, with 39 (53%) identifying significant sex differences and 31 (42%) identifying significant gender differences. However, only three (4%) studies defined sex or gender concepts and only nine (12%) studies used sex or gender terms appropriately. Fifty‐six (76%) studies had more female participants than males. Four (5%) were intervention studies. Studies did not report falls in line with guidelines nor use common fall definitions. Conclusion: Sex and gender differences are commonly reported in falls literature. It is critical for future research to use sex and gender terms appropriately and include similar sample sizes across all genders and sexes. In addition, there is a need to examine more gender‐diverse populations and to develop interventions to prevent falls that address sex and gender differences among older adults. [ABSTRACT FROM AUTHOR]

Racism is hardly discussed in Spanish public debates: however, when approached through policy, it is generally understood either as violent acts committed by extremists, or as a matter of stereotypes/prejudices/lack of information about cultural Others. This article focuses on the latter understanding, as performed by Spanish "anti-rumour" strategies, a varied ensemble of initiatives aimed at dismantling stereotypes of migrants and racial minorities, mainly by encouraging better knowledge and empathy. By approaching these initiatives as a representative case of mainstream, psychology-based perspectives on anti-racism and drawing on fieldwork conducted in relevant Spanish locations, I focus on their main assumptions and theoretical/political implications. Despite the heterogeneity of such initiatives, the fieldwork analysis points to common flaws; particularly in the ways their "positive" narratives and allegedly inclusive approaches might foster narrow definitions of racism, silencing its institutional/structural/governmental dimensions and potentially normalizing racist power relations. [ABSTRACT FROM AUTHOR]

Background: The INBUILD study demonstrated the efficacy of nintedanib in the treatment of progressive fibrosing interstitial lung disease different to idiopathic pulmonary fibrosis, including rheumatoid arthritis (RA)-related ILD. Nevertheless, the prevalence of RA-ILD patients that may potentially benefit from nintedanib remains unknown. Objectives and methods: The aim of the present multicentre study was to investigate the prevalence and possible associated factors of fibrosing progressive patterns in a cross-sectional cohort of RA-ILD patients. Results: One hundred and thirty-four RA-ILD patients with a diagnosis of RA-ILD, who were confirmed at high-resolution computed tomography and with a follow-up of at least 24 months, were enrolled. The patients were defined as having a progressive fibrosing ILD in case of a relative decline in forced vital capacity > 10% predicted and/or an increased extent of fibrotic changes on chest imaging in a 24-month period. Respiratory symptoms were excluded to reduce possible bias due to the retrospective interpretation of cough and dyspnea. According to radiologic features, ILD was classified as usual interstitial pneumonia (UIP) in 50.7% of patients, nonspecific interstitial pneumonia in 19.4%, and other patterns in 29.8%. Globally, a fibrosing progressive pattern was recorded in 36.6% of patients (48.5% of patients with a fibrosing pattern) with a significant association to the UIP pattern. Conclusion: We observed that more than a third of RA-ILD patients showed a fibrosing progressive pattern and might benefit from antifibrotic treatment. This study shows some limitations, such as the retrospective design. The exclusion of respiratory symptoms' evaluation might underestimate the prevalence of progressive lung disease but increases the value of results. [ABSTRACT FROM AUTHOR]

We present an extension of our previously developed all-atom force field BILFF (Bio-polymers in Ionic Liquids Force Field) to three different ionic liquids: 1-ethyl-3-methyl-1,2,3-triazolium acetate ([EMTr][OAc]), 1-ethyl-3-methyl-1,2,3-triazolium benzoate ([EMTr][OBz]), and 1-ethyl-3-methylimidazolium benzoate ([EMIm][OBz]). These ionic liquids are of practical importance as they have the ability to dissolve significant amounts of cellulose even at room temperature. Our force field is optimized to accurately reproduce the strong hydrogen bonding in the system with nearly quantum chemical accuracy. A very good agreement between the microstructure of the quantum chemical simulations over a wide temperature range and experimental density data with the results of BILFF were observed. Non-trivial effects, such as the solvation shell structure and π – π stacking of the cations, are also accurately reproduced. Our force field enables accurate simulations of larger systems, such as solvated cellulose in different (aqueous) ionic liquids, and is the first to present the optimized parameters for mixtures of these solvents and water. [ABSTRACT FROM AUTHOR]

Summary: Mentation reports were collected after spontaneous awakenings from morning naps in 18 healthy participants, and associations between sleep stages duration and complexity of recalled mentation were investigated. Participants were continuously recorded with polysomnography and allowed to sleep for a maximum of 2 hr. Mentation reports were classified according to both their complexity (1–6 scale) and their perceived timing of occurrence (Recent or Previous Mentation with respect to the final awakening). The results showed a good level of mentation recall, including different types of mentation with lab‐related stimuli. N1 + N2 duration was positively related to the complexity of Previous Mentation recall, while rapid eye movement sleep duration was negatively related. This suggests that the recall of complex mentation, such as dreaming with a plot, occurring far from awakening may depend on the length of N1 + N2. However, the duration of sleep stages did not predict the complexity of Recent Mentation recall. Nevertheless, 80% of participants who recalled Recent Mentation had a rapid eye movement sleep episode. Half of the participants reported incorporating lab‐related stimuli in their mentation, which positively correlated with both N1 + N2 and rapid eye movement duration. In conclusion, nap sleep architecture is informative about the complexity of dreams perceived as having occurred early during the sleep episode, but not about those perceived as recent. [ABSTRACT FROM AUTHOR]

Background: Recently, the role of nutraceutical compounds in the prevention of human diseases has been rapidly increasing. Here, we aim to evaluate the beneficial effect of dietary supplementation with seven active principles, i.e., lycopene, sulforaphane, silymarin, glutathione, escin, tryptophan, and green tea catechins, on human health. Methods: An extensive search of PubMed and Medline database was performed with the following keywords: "silymarin", "sulforaphane", "lycopene", "green tea catechins", "tryptophan", "glutathione" and "escin" accompanied by the keywords "supplement", "supplementation", and "nutraceutics". All preclinical and clinical trials were considered for this review. Results: One hundred and eighteen full-text articles were eligible for inclusion in this review. The papers examined presented considerable variability due to the wide heterogeneity of dosages administered, population involved, and outcomes pursued. Conclusion: Nutritional supplementation with lycopene, sulforaphane, silymarin, glutathione, escin, tryptophan, and green tea catechins appears to exert a wide range of benefits on human health, ranging from mood and cognition to cardiovascular health, fertility, metabolism, antioxidant, and anti-inflammatory capabilities, as well as potential anticancer effects. Further studies are required to better define the potential synergic effect, optimal dosage, mechanism of action, and tolerability profiles of these substances. [ABSTRACT FROM AUTHOR]

We introduce a nonlinear, nonhierarchical generalization of Derrida's GREM and establish through a Sanov-type large deviation analysis both a Boltzmann–Gibbs principle as well as a Parisi formula for the limiting free energy. In line with the predictions of the Parisi theory, the free energy is given by the minimal value over all Parisi functionals/hierarchical structures in which the original model can be coarse grained. [ABSTRACT FROM AUTHOR]

Background Nonalcoholic fatty liver disease (NAFLD) is frequent in people with human immunodeficiency virus (PWH). The Fibroscan–aspartate aminotransferase (FAST) score was developed to identify patients with nonalcoholic steatohepatitis (NASH) and significant fibrosis. We investigated prevalence of NASH with fibrosis and the value of FAST score in predicting clinical outcomes in PWH. Methods Transient elastography (Fibroscan) was performed in PWH without viral hepatitis coinfection from 4 prospective cohorts. We used FAST >0.35 to diagnose NASH with fibrosis. Incidence and predictors of liver-related outcomes (hepatic decompensation, hepatocellular carcinoma) and extrahepatic events (cancer, cardiovascular disease) were evaluated through survival analysis. Results Of the 1472 PWH included, 8% had FAST >0.35. Higher body mass index (adjusted odds ratio [aOR], 1.21 [95% confidence interval {CI}, 1.14–1.29]), hypertension (aOR, 2.24 [95% CI, 1.16–4.34]), longer time since HIV diagnosis (aOR, 1.82 [95% CI, 1.20–2.76]), and detectable HIV RNA (aOR, 2.22 [95% CI, 1.02–4.85]) were associated with FAST >0.35. A total of 882 patients were followed for a median of 3.8 years (interquartile range, 2.5–4.2 years). Overall, 2.9% and 11.1% developed liver-related and extrahepatic outcomes, respectively. Incidence of liver-related outcomes was higher in patients with FAST >0.35 versus FAST ≤0.35 (45.1 [95% CI, 26.2–77.7] vs 5.0 [95% CI, 2.9–8.6] per 1000 person-years). FAST >0.35 remained an independent predictor of liver-related outcomes (adjusted hazard ratio, 4.97 [95% CI, 1.97–12.51]). Conversely, FAST did not predict extrahepatic events. Conclusions A significant proportion of PWH may have NASH with significant liver fibrosis. FAST score predicts liver-related outcomes and can help management of this high-risk population. [ABSTRACT FROM AUTHOR]

Roman stamped bricks are considered one of the best indicators of the provenance of Roman building materials, contractors and owners, due to the names included in the stamps. They are also a good proxy for understanding part of the supply chain directed towards Rome and the city's peripheral territories; however, hypotheses based on stamps are nevertheless often insufficient for pinpointing production centers, which limits the extent to which the movement of these materials and their makers can be reconstructed. This paper analyses some well-preserved brick assemblages from the Ager Rusellanus in southern Tuscany and reviews previous provenance hypotheses based on the stamps. The results from ceramic petrography and a systematic review of published analyses highlight how combining contextual information with a wellstructured, analytical approach is fundamental for understanding the movement of goods, the nature of the workforce and even the relationship between state-commissioned building works and its agents. [ABSTRACT FROM AUTHOR]

Probiotics have shown a benefit in reducing necrotising enterocolitis in the premature infant, however the study of their effect on premature neonates' neurodevelopment is limited. The aim of our study was to elucidate whether the effect of Bifidobacterium bifidum NCDO 2203 combined with Lactobacillus acidophilus NCDO 1748 could positively impact the neurodevelopment of the preterm neonates. Quasi-experimental comparative study with a combined treatment of probiotics in premature infants < 32 weeks and < 1500 g birth weight, cared for at a level III neonatal unit. The probiotic combination was administered orally to neonates surviving beyond 7 days of life, until 34 weeks postmenstrual age or discharge. Globally, neurodevelopment was evaluated at 24 months corrected age. A total of 233 neonates were recruited, 109 in the probiotic group and 124 in the non-probiotic group. In those neonates receiving probiotics, there was a significant reduction in neurodevelopment impairment at 2 years of age RR 0.30 [0.16–0.58], and a reduction in the degree of impairment (normal-mild vs moderate-severe, RR 0.22 [0.07–0.73]). Additionally, there was a significant reduction in late-onset sepsis (RR 0.45 [0.21–0.99]). The prophylactic use of this probiotic combination contributed to improving neurodevelopmental outcome and reduced sepsis in neonates born at < 32 weeks and < 1500 g.Per style, a structured abstract is not allowed so we have changed the structured abstract to an unstructured abstract. Please check and confirm.Accepted [ABSTRACT FROM AUTHOR]

Many fundamental chemical reactions are triggered by electronic excitations. Here, we propose and benchmark a novel approximate first-principles molecular dynamics simulation idea for increasing the computational efficiency of density functional theory-based calculations of the excited states. We focus on obtaining proton transfer energy at the S1 excited state through actual density functional theory calculations at the T1 state with additional optimized effective potentials. The potentials are optimized as such to reproduce the excited-state energy surface obtained using time-dependent density functional theory, but can be generalized to other more accurate quantum chemical methods. We believe that the presented method is not only suitable for studies on excited-state proton transfer and ion mobility in general systems but can also be extended to investigate more involved processes, such as photo-induced isomerization. [ABSTRACT FROM AUTHOR]

We analyze a class of topological static spherically symmetric vacuum solutions in f(Q)-gravity. We considered an Ansatz ensuring that those solutions trivially satisfy the field equations of the theory when the non-metricity scalar is constant. In the specific, we provide and discuss local solutions in the form of black holes and traversable wormholes. [ABSTRACT FROM AUTHOR]

Monoderm bacteria accumulate heme b via the coproporphyrin-dependent biosynthesis pathway. In the final step, in the presence of two molecules of H2O2, the propionate groups of coproheme at positions 2 and 4 are decarboxylated to form vinyl groups by coproheme decarboxylase (ChdC), in a stepwise process. Decarboxylation of propionate 2 produces an intermediate that rotates by 90° inside the protein pocket, bringing propionate 4 near the catalytic tyrosine, to allow the second decarboxylation step. The active site of ChdCs is stabilized by an extensive H-bond network involving water molecules, specific amino acid residues, and the propionate groups of the porphyrin. To evaluate the role of these H-bonds in the pocket stability and enzyme functionality, we characterized, via resonance Raman and electronic absorption spectroscopies, single and double mutants of the actinobacterial pathogen Corynebacterium diphtheriae ChdC complexed with coproheme and heme b. The selective elimination of the H-bond interactions between propionates 2, 4, 6, and 7 and the polar residues of the pocket allowed us to establish the role of each H-bond in the catalytic reaction and to follow the changes in the interactions from the substrate to the product. [ABSTRACT FROM AUTHOR]

The diversity of monosaccharides and glycosidic linkages of extracellular polysaccharide (EPS) of high molecular weight were studied in strains morphologically assigned to the genus Ankistrodesmus. EPSs of seven strains were similar in both monosaccharides and glycosidic linkages, but showed exclusive characteristics or enough differences in proportions to distinguish strains. Fucose, glucose, rhamnose, mannose and galactose occurred in relatively high percentages in all strains. The strain CCMA-UFSCar 423, excluded from the genus Ankistrodesmus by the molecular marker tufA, was the only one containing galacturonic acid. Arabinose was found only in one A. densus strain (CCMA-UFSCar 239). The species A. densus and A. stipitatus, which are known to have, respectively, stable mucilaginous capsules and pads in aqueous media, presented high percentages of the hydrophobic fucose and rhamnose on their polysaccharides. However, the strain CCMA-UFSCar 83, the only non-colonial A. densus, had low proportions of rhamnose. We also found variations in glycosidic linkages, and some of them were specific to one strain (e.g. 1-3 glucose in A. stipitatus). Conversely, the absence of common linkages was noteworthy for the strain outside the Ankistrodesmus clade, the CCMA-UFSCar 423. The data revealed important diversity in monosaccharides and linkages of the EPS within a single microalgae genus, and an important intraspecific diversity using a single growing condition. These differences could be useful as potential chemotaxonomic tools to help discriminating the Ankistrodesmus genus or species, but also for future studies on intraspecific diversity within the genus. Moreover, the results show the relevance of studying and conserving closely related strains to preserve biodiversity. The diverse composition of high molecular weight EPSs shows a great potential for prospecting EPSs of economic interest. [ABSTRACT FROM AUTHOR]

The IEC standards describe how to measure the power performance of an isolated wake-free wind turbine. However, most wind turbines operate under waked conditions for a substantial amount of time, calling for the need of a new methodology for power performance evaluation. We define multivariate power curves in the form of multivariate polynomial regressions, whose input variables are several wind speed and turbulence measurements retrieved with nacelle lidars. We use a dataset of synthetic power performance tests including both waked and wake-free conditions. The dataset is generated through aeroelastic simulations combined with both virtual nacelle lidars and the dynamic wake meandering model. A feature-selection algorithm is used to select the input variables among the available measurements, showing that the optimal model includes four input variables: three correspondent to wind speed and one to turbulence measures. Additionally, we give insights on the optimal nacelle-lidar scanning geometry needed to implement the multivariate power curve. Results show that the multivariate power curves predict the power output with accuracy of the same order under both waked and wake-free operation. For the in-wake cases, the accuracy is much higher than that of the IEC standard power curve, with an error reduction of up to 88%. • Aeroelastic simulations combined with a wake model and virtual nacelle lidars. • Modelling wind turbine power curves as multivariable polynomial regressions. • Several nacelle lidar configurations are tested. • The multivariate power curves are more accurate than the IEC standard power curve. • The multivariate power curves are as accurate in wake as in wake-free conditions. [ABSTRACT FROM AUTHOR]

Background: Fat alterations are frequent in people with HIV (PWH) and predict worse cardiometabolic outcomes. Visceral adipose tissue (VAT) is associated with ectopic fat accumulation in the liver. We aimed to investigate nonalcoholic fatty liver disease (NAFLD) diagnosed by controlled attenuation parameter (CAP) as a potential marker of visceral adiposity in PWH. Methods: We conducted a prospective pilot study of HIV mono-infected patients undergoing metabolic characterization and paired CAP measured by transient elastography with dual-energy X-ray absorptiometry (DEXA) scan. NAFLD was defined as CAP ≥ 285 dB/m, in absence of alcohol abuse. Excess visceral adiposity was defined as VAT > 1.32 Kg. Pairwise correlation, area under the curve (AUC) and logistic regression analysis were employed to study the association between VAT and CAP. Results: Thirty patients were included, of whom 50% had NAFLD. CAP was correlated with VAT (r = 0.650, p < 0.001) measured by DEXA scan. After adjusting for duration of HIV infection, body mass index and waist circumference, CAP remained the only independent predictor of excess VAT (adjusted odds ratio 1.05, 95% confidence interval [CI] 1.01–1.10). The AUC analysis determined CAP had excellent performance to diagnose excess VAT (AUC 0.92, 95% CI 0.81–1.00), higher than BMI and waist circumference. The optimized CAP cut-off to diagnose excess VAT was 266 dB/m, with a sensitivity of 88.3% and a specificity of 84.6%. Conclusions: NAFLD diagnosed by CAP is associated with VAT in PWH independently of anthropometric measures of obesity. CAP may be a potential diagnostic marker of visceral adiposity in the practice of HIV medicine. [ABSTRACT FROM AUTHOR]

Solid phases of water, such as ice (Ih) and clathrate hydrates, form characteristic hydrogen bond network motifs, such as hexagonal ice, pentagons, and dodecahedrons. The same motifs might be present in supercooled water and in the hydration structure around hydrophobes. Here, we present the characteristic low frequency fingerprints of ice (Ih), tetrahydrofuran (THF) clathrate hydrates, and tetrabutyl-ammonium bromide (TBAB) semiclathrate close to their melting point, as well as supercooled water at 266.6 K and aqueous alcohol solutions. Interestingly, we find in all these cases two characteristic resonances in the THz frequency range: at least, one intensive band in the frequency range between 190 cm−1 and 220 cm−1 which is a characteristic of a tetrahedral hydrogen bond network configuration and a second band in the frequency range between 140 cm−1 and 170 cm−1, indicating a component with weaker hydrogen bonds. For solvated alcohols, we find spectroscopic fingerprints of a clathratelike structure at 164 cm−1 as well as a tetrahedral network structure at 194 cm−1, which is close to one of ice (Ih) at 192 cm−1. We propose that in the hydration shell of hydrophobes, both structural motifs are present. In the case of supercooled water—unlike ice—only one peak was found in the frequency range between 190 cm−1 and 220 cm−1. Interestingly, the latter peak center-frequency (204 cm−1) corresponds to the average of those of the two peaks observed for ice Ih (191 cm−1 and 215 cm−1). This indicates a homogeneous intermediate hydrogen bonding, providing no evidence for any heterogeneity in two high-density and low-density phases. [ABSTRACT FROM AUTHOR]

In this paper, we problematise the relationship between racism and immigrant integration policies. First, we approach racism from its geopolitical/institutional/governmental logic and contextualise the emergence of integration policies across the European Union. Then, we put into dialogue the fieldwork materials of our research projects, analysing intersections between the EU and Spanish integration policy frameworks. Despite the inclusive and proactive rhetoric often expressed by integration policies, we illustrate the existence of an 'elective affinity' between racism and integration by focusing on: (1) the construction of migrants as a problematic 'object' of governmental intervention; (2) the reduction of racism to an individual pathology and the underestimation of its institutional/structural dimensions; (3) the reproduction of epistemic racism through the discourse on European (and national) values. [ABSTRACT FROM AUTHOR]

Sentiment quantification is the task of training, by means of supervised learning, estimators of the relative frequency (also called "prevalence") of sentiment-related classes (such as Positive, Neutral, Negative) in a sample of unlabelled texts. This task is especially important when these texts are tweets, since the final goal of most sentiment classification efforts carried out on Twitter data is actually quantification (and not the classification of individual tweets). It is well-known that solving quantification by means of "classify and count" (i.e., by classifying all unlabelled items by means of a standard classifier and counting the items that have been assigned to a given class) is less than optimal in terms of accuracy, and that more accurate quantification methods exist. Gao and Sebastiani 2016 carried out a systematic comparison of quantification methods on the task of tweet sentiment quantification. In hindsight, we observe that the experimentation carried out in that work was weak, and that the reliability of the conclusions that were drawn from the results is thus questionable. We here re-evaluate those quantification methods (plus a few more modern ones) on exactly the same datasets, this time following a now consolidated and robust experimental protocol (which also involves simulating the presence, in the test data, of class prevalence values very different from those of the training set). This experimental protocol (even without counting the newly added methods) involves a number of experiments 5,775 times larger than that of the original study. Due to the above-mentioned presence, in the test data, of samples characterised by class prevalence values very different from those of the training set, the results of our experiments are dramatically different from those obtained by Gao and Sebastiani, and provide a different, much more solid understanding of the relative strengths and weaknesses of different sentiment quantification methods. [ABSTRACT FROM AUTHOR]

Objectives: Non‐alcoholic fatty liver disease (NAFLD) is strongly associated with cardiovascular disease in the general population. We aimed to assess the impact of NAFLD and liver fibrosis on intermediate‐high cardiovascular risk in people living with HIV. Methods: We included people living with HIV from three cohorts. NAFLD and significant liver fibrosis were defined using transient elastography: controlled attenuation parameter ≥288 dB/m and liver stiffness measurement ≥7.1 kPa, respectively. Cardiovascular risk was assessed with the atherosclerotic cardiovascular disease (ASCVD) risk estimator in patients aged between 40 and 75 years and categorised as low if <5%, borderline if 5%–7.4%, intermediate if 7.5%–19.9% and high if ≥20% or with the presence of a previous cardiovascular event. Patients with hepatitis B and/or hepatitis C virus co‐infection, alcohol abuse and unreliable transient elastography measurements were excluded. Predictors of intermediate‐high cardiovascular risk were investigated in multivariable analysis by logistic regression and also by stratifying according to body mass index (BMI; cut‐offs of 25 and 30 kg/m2) and age (cut‐off of 60 years). Results: Of 941 patients with HIV alone included, 423 (45%), 128 (13.6%), 260 (27.6%) and 130 (13.8%) were categorised as at low, borderline, intermediate and high ASCVD risk, respectively. Predictors of intermediate‐high ASCVD risk were NAFLD (adjusted odds ratio [aOR] 2.11; 95% confidence interval [CI] 1.40–3.18; p < 0.001), liver fibrosis (aOR 1.64; 95% CI 1.03–2.59; p = 0.034), duration of HIV (aOR 1.04; 95% CI 1.02–1.06; p < 0.001), and previous exposure to thymidine analogues and/or didanosine (aOR 1.54; 95% CI 1.09–2.18; p = 0.014). NAFLD was also associated with higher cardiovascular risk in normoweight patients (aOR 2.97; 95% CI 1.43–6.16; p = 0.003), in those with BMI <30 kg/m2 (aOR 2.30; 95% CI 1.46–3.61; p < 0.001) and in those aged <60 years (aOR 2.19; 95% CI 1.36–3.54; p = 0.001). Conclusion: Assessment of cardiovascular disease should be targeted in people living with HIV with NAFLD and/or significant liver fibrosis, even if they are normoweight and young. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD), alcohol-induced liver disease (ALD), and viral hepatitis are the main causes of morbidity and mortality related to chronic liver diseases (CLDs) worldwide. New therapeutic approaches to prevent or reverse these liver disorders are thus emerging. Although their etiologies differ, these CLDs all have in common a significant dysregulation of liver metabolism that is closely linked to the perturbation of the hepatic endocannabinoid system (eCBS) and inflammatory pathways. Therefore, targeting the hepatic eCBS might have promising therapeutic potential to overcome CLDs. Experimental models of CLDs and observational studies in humans suggest that cannabis and its derivatives may exert hepatoprotective effects against CLDs through diverse pathways. However, these promising therapeutic benefits are not yet fully validated, as the few completed clinical trials on phytocannabinoids, which are thought to hold the most promising therapeutic potential (cannabidiol or tetrahydrocannabivarin), remained inconclusive. Therefore, expanding research on less studied phytocannabinoids and their derivatives, with a focus on their mode of action on liver metabolism, might provide promising advances in the development of new and original therapeutics for the management of CLDs, such as NAFLD, ALD, or even hepatitis C-induced liver disorders. [ABSTRACT FROM AUTHOR]

Most wind turbines are installed inside wind farms, where they often operate under wake-affected inflow conditions. New methods are required to evaluate the power performance of a wind turbine in wake, as the International Electrotechnical Commission (IEC) standard procedure is applicable only to wake-free turbines. In this work, we investigate the accuracy of a multivariate power curve acquired through a polynomial regression, whose input variables are wind speed and turbulence measurements retrieved upstream of the turbine's rotor. For this purpose, we use measurements from the SpinnerLidar, a continuous-wave, scanning Doppler lidar measuring the turbine inflow. The SpinnerLidar was mounted in the spinner of a Neg Micon 80 wind turbine located within an onshore wind farm in western Denmark. The input variables are selected among the available lidar measurements with a feature-selection algorithm, resulting in seven input variables, distributed in different locations along the rotor area: six wind speed and one turbulence measurements. The multivariate power curve is tested and compared with IEC-similar power curves under both wake-affected and wake-free conditions. Results show that the multivariate power curve estimates the turbine's power output more accurately than the IEC-similar power curves, with error reductions up to 66.5% and 34.2% under wake-affected and wake-free conditions, respectively. Furthermore, the multivariate power curve estimates have an accuracy of the same order under both wake-affected and wake-free conditions. Finally, we show that the multivariate model accurately predicts the power even when a simple measuring geometry is used, such as circular scanning pattern with a diameter equal to 90% of the rotor. • Measurements from a spinner-mounted lidar under wake conditions. • Wind speed and turbulence retrieved from lidar Doppler radial velocity spectra. • Wind turbine power curves modelled as multivariable polynomial regressions. • The multivariate power curves are more accurate than the IEC binning method. • The multivariate power curves are as accurate in wake as in wake-free conditions. [ABSTRACT FROM AUTHOR]

[Display omitted] • Ferrochelatases insert ferrous iron in porphyrins in the heme biosynthesis pathway. • The porphyrin proximal ligand is not conserved in the active site of ferrochelatases. • Proximal mutations alter the H-bonds between the porphyrin and the protein. • Effects on the activity are induced by the polarity of the mutated proximal ligand. • The weak coordination by the proximal ligand is essential for substrate and product. Ferrochelatases catalyze the insertion of ferrous iron into the porphyrin during the heme b biosynthesis pathway, which is fundamental for both prokaryotes and eukaryotes. Interestingly, in the active site of ferrochelatases, the proximal ligand coordinating the porphyrin iron of the product is not conserved, and its catalytic role is still unclear. Here we compare the L. monocytogenes bacterial coproporphyrin ferrochelatase native enzyme together with selected variants, where the proximal Tyr residue was replaced by a His (i.e. the most common ligand in heme proteins), a Met or a Phe (as in human and actinobacterial ferrochelatases, respectively), in their Fe(III), Fe(II) and Fe(II)–CO adduct forms. The study of the active site structure and the activity of the proteins in solution has been performed by UV–vis electronic absorption and resonance Raman spectroscopies, biochemical characterization, and classical MD simulations. All the mutations alter the H-bond interactions between the iron porphyrin propionate groups and the protein, and induce effects on the activity, depending on the polarity of the proximal ligand. The overall results confirm that the weak or non-existing coordination of the porphyrin iron by the proximal residue is essential for the binding of the substrate and the release of the final product. [ABSTRACT FROM AUTHOR]

Plastic-fluidized bed interaction has been investigated by non-invasive X-ray imaging techniques in the temperature range of 500–650 °C and under pyrolysis conditions. Experiments were conducted by feeding a single polypropylene particle using either overbed or underbed feeding methods. The fluidized bed was operated from minimum fluidization conditions to bubbling regime, up to 2U mf. Interestingly, experimental observations show that the understanding of the mixing/segregation behaviour of polypropylene in a hot fluidized bed does not appear to be as straightforward as in the case of more conventional feedstocks, such as biomass. Further analysis and an alternative point of view to investigate the complex behaviour observed for plastic feedstock have been provided. The interaction between the fluidized bed and a single polypropylene particle was modelled by means of an axial segregation model, and a physics-assisted stochastic approach. In the second case, it was possible to simulate the formation of the sand-plastic agglomerate (incipient agglomeration stage) and the evolution of its density over time. The models were then validated by means of axial segregation data obtained via X-ray imaging techniques and by measuring the physical properties of real sand-polypropylene agglomerates produced within the bed operating at high temperatures. Results obtained in this study show that the unpredictable sinking-floating behaviour of the plastic particles is not related to the change in density associated to the formation of the sand-polypropylene agglomerates over time. [Display omitted] • The plastic-sand incipient agglomeration in a BFBR is investigated. • X-ray observations reveal the segregation behaviour of polypropylene particles. • Polypropylene particles settle at the bottom of the bed after under bed feeding. • A Monte Carlo-based agglomeration model is developed to predict agglomeration. • Surface tension forces may dominate over gravitational forces for molten plastics. [ABSTRACT FROM AUTHOR]

To investigate the structure and dynamics of small ionic liquid droplets in gas phase, we performed a DFT-based ab initio molecular dynamics study of several 1-ethyl-3-methylimidazolium acetate clusters in vacuum as well as a bulk phase simulation. We introduce an unbiased criterion for average droplet diameter and density. By extrapolation of the droplet densities, we predict the experimental bulk phase density with a deviation of only a few percent. The hydrogen bond geometry between cations and anions is very similar in droplets and bulk, but the hydrogen bond dynamics is significantly slower in the droplets, becoming slower with increasing system size, with hydrogen bond lifetimes up to 2000 ps. From a normal mode analysis of the trajectories, we identify the modes of the ring proton C–H stretching, which are strongly affected by hydrogen bonding. From analyzing these, we find that the hydrogen bond becomes weaker with increasing system size. The cations possess an increased concentration inside the clusters, whereas the anions show an excess concentration on the outside. Almost all anions point towards the droplet center with their carboxylic groups. Ring stacking is found to be a very important structural motif in the droplets (as in the bulk), but side chain interactions are only of minor importance. By using Voronoi tessellation, we define the exposed droplet surface and find that it consists mainly of hydrogen atoms from the cation’s and anion’s methyl and ethyl groups. Polar atoms are rarely found on the surface, such that the droplets appear completely hydrophobic on the outside. [ABSTRACT FROM AUTHOR]

Hydration free energies are dictated by a subtle balance of hydrophobic and hydrophilic interactions. We present here a spectroscopic approach, which gives direct access to the two main contributions: Using THz‐spectroscopy to probe the frequency range of the intermolecular stretch (150–200 cm−1) and the hindered rotations (450–600 cm−1), the local contributions due to cavity formation and hydrophilic interactions can be traced back. We show that via THz calorimetry these fingerprints can be correlated 1 : 1 with the group specific solvation entropy and enthalpy. This allows to deduce separately the hydrophobic (i.e. cavity formation) and hydrophilic contributions to thermodynamics, as shown for hydrated alcohols as a case study. Accompanying molecular dynamics simulations quantitatively support our experimental results. In the future our approach will allow to dissect hydration contributions in inhomogeneous mixtures and under non‐equilibrium conditions. [ABSTRACT FROM AUTHOR]

Hydration free energies are dictated by a subtle balance of hydrophobic and hydrophilic interactions. We present here a spectroscopic approach, which gives direct access to the two main contributions: Using THz‐spectroscopy to probe the frequency range of the intermolecular stretch (150–200 cm−1) and the hindered rotations (450–600 cm−1), the local contributions due to cavity formation and hydrophilic interactions can be traced back. We show that via THz calorimetry these fingerprints can be correlated 1 : 1 with the group specific solvation entropy and enthalpy. This allows to deduce separately the hydrophobic (i.e. cavity formation) and hydrophilic contributions to thermodynamics, as shown for hydrated alcohols as a case study. Accompanying molecular dynamics simulations quantitatively support our experimental results. In the future our approach will allow to dissect hydration contributions in inhomogeneous mixtures and under non‐equilibrium conditions. [ABSTRACT FROM AUTHOR]

In this regard, since about half of RA patients show low or absent CD20+ B cells in affected synovia, it has been postulated that the level of synovial B cells/B cell-related pathways would influence the treatment response to anti-CD20 monoclonal antibodies, namely rituximab. In the last ten years, many advances have been made in the treatment and diagnosis of immune-mediated diseases. The methodology involved patient stratification to ameliorate the diagnosis and treatment outcomes by stratifying patients within a single disease. However, the majority of RA patients do not respond to methotrexate and about 40% even to the first biological or targeted synthetic DMARD; finally, 5-20% of RA patients are resistant to all current medications, and recently, many authors have defined these groups of patients as "difficult to treat RA" [[9]]. [Extracted from the article]

The actinobacterial coproheme decarboxylase from Corynebacterium diphtheriae catalyzes the final reaction to generate heme b via the "coproporphyrin‐dependent" heme biosynthesis pathway in the presence of hydrogen peroxide. The enzyme has a high reactivity toward H2O2 used for the catalytic reaction and in the presence of an excess of H2O2 new species are generated. Resonance Raman data, together with electronic absorption spectroscopy and mass spectrometry, indicate that an excess of hydrogen peroxide for both the substrate (coproheme) and product (heme b) complexes of this enzyme causes a porphyrin hydroxylation of ring C or D, which is compatible with the formation of an iron chlorin‐type heme d species. A similar effect has been previously observed for other heme‐containing proteins, but this is the first time that a similar mechanism is reported for a coproheme enzyme. The hydroxylation determines a symmetry lowering of the porphyrin macrocycle, which causes the activation of A2g modes upon Soret excitation with a significant change in their polarization ratios, the enhancement and splitting into two components of many Eu bands, and an intensity decrease of the non‐totally symmetric modes B1g, which become polarized. This latter effect is clearly observed for the isolated ν10 mode upon either Soret or Q‐band excitations. The distal His118 is shown to be an absolute requirement for the conversion to heme d. This residue also plays an important role in the oxidative decarboxylation, because it acts as a base for deprotonation and subsequent heterolytic cleavage of hydrogen peroxide. [ABSTRACT FROM AUTHOR]

We study the influence of rotational coupling between a pair of methyl rotators on the tunneling spectrum in condensed phase. Two interacting adjacent methyl groups are simulated within a coupled-pair model composed of static rotational potential created by the chemical environment and the interaction potential between two methyl groups. We solve the two-dimensional time-independent Schrödinger equation analytically by expanding the wave functions on the basis set of two independent free-rotor functions. We investigate three scenarios which differ with respect to the relative strength of single-rotor and coupling potential. For each scenario, we illustrate the dependence of the energy level scheme on the coupling strength. It is found that the main determinant of splitting energy levels tends to be a function of the ratio of strengths of coupling and single-rotor potential. The tunnel splitting caused by coupling is maximized for the coupled rotors in which their total hindering potential is relatively shallow. Such a weakly hindered methyl rotational potential is predicted for 4-methylpyridine at low temperature. The experimental observation of multiple tunneling peaks arising from a single type of methyl group in 4-methylpyridine in the inelastic neutron scattering spectrum is widely attributed to the rotor-rotor coupling. In this regard, using a set of first-principles calculations combined with the nudged elastic band method, we investigate the rotational potential energy surface (PES) of the coaxial pairs of rotors in 4-methylpyridine. A Numerov-type method is used to numerically solve the two-dimensional time-independent Schrödinger equation for the calculated 2D-density functional theory profile. Our computed energy levels reproduce the observed tunneling transitions well. Moreover, the calculated density distribution of the three methyl protons resembles the experimental nuclear densities obtained from the Fourier difference method. By mapping the calculated first-principles PES on the model, it is confirmed that the hindering potential in 4-methylpyridine consists of proportionally shallow single-rotor potential to coupling interaction. [ABSTRACT FROM AUTHOR]

Many studies highlighted potential associations of β-casein A1 with specific human diseases and a minor digestibility of milk, due to the bioactive peptide β-casomorphin 7 (BCM-7) release during digestion. Conversely, the ancestral β-casein A2 variant seems to be a favorable trait because it is not associated with BMC-7 release. The aim of this work was to evaluate frequencies of β-casein variants in offspring of previously genotyped cows inseminated with A2 homozygous semen. The frequency of the A2/A2 animals has almost doubled from 37 to 69%. These are encouraging results with the perspective of reaching the goal of producing A2 milk. [ABSTRACT FROM AUTHOR]

[Display omitted] • Time and cost-effective method for screening of serum protein binding to lipid nanoparticles based on Quartz Crystal Microbalance with Dissipation. • Sensor coating for detection of specific protein on a lipid-protein assembly. • Sensor coating for immobilisation of pegylated lipid assembly. • Lipid nanoparticle formulation affects serum protein binding affinity. Lipid nanoparticles (LNPs) are promising drug and gene carriers. Upon intravenous administration, LNPs' experience different degree of cellular uptake depending on their formulation. Currently, in vitro and in vivo studies are the gold standard for assessing the fate of nano carriers once administered, but they are time consuming and expensive. In this work, we propose a time and cost-effective method to screen a wide range of LNP formulations and select the most promising candidates for in vitro and in vivo studies. Two different approaches were explored to investigate the binding affinity between LNPs and serum proteins using sensor functionalisation with either protein specific antibody or PEG specific antibody. The first approach allowed to identify the presence of a specific protein in the protein corona of lipid particles (reconstituted and native high-density lipoproteins (rHDL and HDL), and low-density lipoproteins LDL); while the second one provided a versatile platform for the immobilisation of pegylated-particles in order to follow the interaction with serum proteins and hence predict the composition of LNP protein corona. Sensing was done using Quartz Crystal Microbalance with Dissipation (QCM-D) but the approach is extendable to other surface sensing techniques such as Surface Plasmon Resonance (SPR) or ellipsometry. [ABSTRACT FROM AUTHOR]

Coproporpyhrin III is the substrate of coproporphyrin ferrochelatases (CpfCs). These enzymes catalyse the insertion of ferrous iron into the porphyrin ring. This is the penultimate step within the coproporphyrin‐dependent haeme biosynthesis pathway. This pathway was discovered in 2015 and is mainly utilised by monoderm bacteria. Prior to this discovery, monoderm bacteria were believed to utilise the protoporphyrin‐dependent pathway, analogously to diderm bacteria, where the substrate for the respective ferrochelatase is protoporphyrin IX, which has two propionate groups at positions 6 and 7 and two vinyl groups at positions 2 and 4. In this work, we describe for the first time the interactions of the four‐propionate substrate, coproporphyrin III, and the four‐propionate product, iron coproporphyrin III (coproheme), with the CpfC from Listeria monocytogenes and pin down differences with respect to the protoporphyrin IX and haeme b complexes in the wild‐type (WT) enzyme. We further created seven LmCpfC variants aiming at altering substrate and product coordination. The WT enzyme and all the variants were comparatively studied by spectroscopic, thermodynamic and kinetic means to investigate in detail the H‐bonding interactions, which govern complex stability and substrate specificity. We identified a tyrosine residue (Y124 in LmCpfC), coordinating the propionate at position 2, which is conserved in monoderm CpfCs, to be highly important for binding and stabilisation. Importantly, we also describe a tyrosine‐serine‐threonine triad, which coordinates the propionate at position 4. The study of the triad variants indicates structural differences between the coproporphyrin III and the coproheme complexes. Enzyme: EC 4.99.1.9 [ABSTRACT FROM AUTHOR]

Background: The benzodiazepine midazolam is a γ-aminobutyric acid (GABA)-A receptor agonist frequently used for sedation or stress control in patients suffering from traumatic brain injury (TBI). However, experimental studies on benzodiazepines have reported divergent results, raising concerns about its widespread use in patients. Some studies indicate that benzodiazepine-mediated potentiation of GABAergic neurotransmission is detrimental in brain-injured animals. However, other experimental investigations demonstrate neuroprotective effects, especially in pretreatment paradigms. This study investigated whether single-bolus midazolam administration influences secondary brain damage post-TBI. Methods: Two different midazolam dosages (0.5 and 5 mg/kg BW), a combination of midazolam and its competitive antagonist flumazenil, or vehicle solution (NaCl 0.9%) was injected intravenously to mice 24 h after experimental TBI induced by controlled cortical impact. Mice were evaluated for neurological and motor deficits using a 15-point neuroscore and the rotarod test. Histopathological brain damage and mRNA expression of inflammatory marker genes were analyzed using quantitative polymerase chain reaction three days after insult. Results: Histological brain damage was not affected by posttraumatic midazolam administration. Midazolam impaired functional recovery, and this effect could not be counteracted by administering the midazolam antagonist flumazenil. An increase in IL-1β mRNA levels due to postinjury application of midazolam was reversible by flumazenil administration. However, other inflammatory parameters were not affected. Conclusions: This study merely reports minor effects of a postinjury midazolam application. Further studies focusing on a time-dependent analysis of posttraumatic benzodiazepine administration are required. [ABSTRACT FROM AUTHOR]

Interstitial lung disease (ILD) is a cause of morbidity and mortality in patients with rheumatic diseases, such as connective-tissue diseases, rheumatoid arthritis and systemic vasculitis. Some patients with ILD secondary to rheumatic disease (RD-ILD) experience acute exacerbations, with sudden ILD progression and high mortality during or immediately after the exacerbation, and a very low 1-year survival rate. In the ILD subtype idiopathic pulmonary fibrosis (IPF), an acute exacerbation is defined as acute worsening or development of dyspnoea associated with new bilateral ground-glass opacities and/or consolidations at high-resolution CT, superimposed on a background pattern consistent with fibrosing ILD. However, acute exacerbation in RD-ILD (AE-RD-ILD) currently has no specific definition. The aetiology and pathogenesis of AE-RD-ILD remain unclear, but distinct triggers might include infection, mechanical stress, microaspiration and DMARD treatment. At this time, no effective evidence-based therapeutic strategies for AE-RD-ILD are available. In clinical practice, AE-RD-ILD is often empirically treated with high-dose systemic steroids and antibiotics, with or without immunosuppressive drugs. In this Review, we summarize the clinical features, diagnosis, management and prognosis of AE-RD-ILD, enabling the similarities and differences with acute exacerbation in IPF to be critically assessed. [ABSTRACT FROM AUTHOR]

• ES provision improves outside the urban cores and along the urban–rural gradients. • ES coldspots are consistently found inside capital municipalities. • In four MCs all four ESs form synergies and are provided as a bundle. • Greening should target protected areas inside coldspots. • Interventions should be aimed at increasing connectivity between hotspots. Over the last decades, the environmental burden borne by natural ecosystems to sustain life in urban areas has considerably increased. For this reason, the network of interconnected green areas and features, referred to as Urban Green Infrastructure, is increasingly being promoted as a valuable means to enhance the life quality of city dwellers by providing Ecosystem Services. We present a spatial analysis of Ecosystem Services provision and synergies/trade-offs along the urban–rural gradient for the following Italian coastal Metropolitan cities: Genoa, Rome, Bari, Naples, Cagliari, Reggio Calabria and Palermo. We focused our attention on three macro classes of human-induced environmental pressures that are particularly critical to the quality of life in urban contexts, namely air pollution, Urban Heat Island effect, and alteration of the water cycle. We found that all of the selected Ecosystem Services, besides a few exceptions, are provided as a bundle, which means they appear together repeatedly, forming an association. On average, the Ecosystem Services provision grows at comparable paces moving from the inner urban core towards the peri-urban and rural areas. As a consequence, most densely urbanized areas were found to be Ecosystem Services coldspots compared to peri-urban and rural areas. [ABSTRACT FROM AUTHOR]

Using a set of first-principles calculations, we have studied the methyl tunnel splitting for molecular crystals of -picoline and toluene. The effective rotational potential energy surface of the probe methyl rotor along the tunneling path is evaluated using first-principles electronic structure calculations combined with the nudged elastic band method. The tunnel splitting is calculated by an explicit diagonalization of the one-dimensional time-independent Hamiltonian matrix. The effects of chemical environment and rotor-rotor coupling on the rotational energy barriers were investigated. It is found that more dense packing of the molecules in toluene compared to that in -picoline gives rise to a larger rotational barrier which in turn yields a considerably smaller tunnel splitting. Moreover, it turned out that coupled motion of the face-to-face methyl groups in -picoline has a significant effect on the reduction of the rotational barrier. Our results are in good agreement with the experimentally observed tunnel splitting. [ABSTRACT FROM AUTHOR]

This study has analysed and optimised a 5-column sorption enhanced water gas shift (SEWGS) pilot unit, set to operate for the first time in a waste gasification facility for the production of transport-grade hydrogen and CO 2 streams. Full process simulation was undertaken by developing a one-dimensional model of each reactor, with boundary conditions directly informed by real plant operation. From the sensitivity analysis performed, syngas flowrate variations were seen to have a minor but temporary, impact on hydrogen product specifications, while changes to syngas composition were shown to have a longer-lasting effect on system performance. Based on full cycle operation results, the current 5-column SEWGS unit design was concluded to be inadequate for fuel-cell-grade H 2 production, despite obtaining a high H 2 purity of 99.5%, mainly due to its excessive steam consumption. However, the process achieved an exceptionally high CO 2 purity of 99.9%, and 88.6% hydrogen recovery rate, suggesting its potential use in carbon capture and heat-grade hydrogen production applications. • Simulation of sorption enhanced water gas shift pilot fed by waste-derived syngas. • Boundary conditions directly informed from real waste gasification plant. • Low-pressure operation as promising way for process intensification. • Sensitivity analysis by varying syngas feed and composition as real disturbances. • 99.9% and 99.5% purities of CO 2 and H 2 products, respectively. [ABSTRACT FROM AUTHOR]

In Spain, (anti-)racism is of scarce relevance to public debates and, when the topic is broached, it has mainly been discussed in relation to non-EU migration. Besides, its historical link with colonialism generally remains unacknowledged. This article analyses the problematisation of 'race' and 'racism' in this context, as performed by hegemonic stakeholders (i.e. public servants, NGOs, experts) in the fields of anti-discrimination, Roma inclusion and immigrant integration policies. As the fieldwork materials illustrate, this understanding rejects 'race' not only from a scientific-biological perspective but also as a social-political category. Accordingly, racism is depoliticised and theorised in a twofold manner: (1) as a matter of stereotypes, prejudices and lack of information about the 'Other'; (2) as the aggressive acts of explicitly racist individuals/organisations. The structural, historical and institutional dimensions of racism are addressed either as background context, or they are negated by public policies. By not confronting the uneven power relations (re)produced by racism, this approach reaffirms 'institutional whiteness' as the underlying perspective of mainstream Spanish anti-racism. [ABSTRACT FROM AUTHOR]

The erudite James Burnet, Lord Monboddo (1714–1799), member of the Select Society and judge of the Court of Session in Edinburgh, wrote many pages about the existence of 'men with tails' and orang-utans' humanity. For this reason, he has been labelled as 'credulous', 'bizarre' and 'eccentric' both by his contemporaries and by modern scholars. In this paper, I shall try to take his argument seriously and to show that throughout his work Monboddo searched for evidence. If his belief in mermaids, giants, blemmyes, daemons and oracles was far from reflecting the general attitude of the age of Enlightenment and empiricism, Monboddo contributed to place the 'science of man' at the centre of the map of knowledge, where Nicholas Phillipson had also located it. He did this by emphasising the variety and historicity of humankind and stressing how mind and body changed over time and space. This article is also an attempt to connect Monboddo's erudite production with his position as a lawyer and a judge. I shall argue that Monboddo founded his 'science of man' on an epistemology of legal evidence, employing the same inquisitive approach that he practiced at the bar and in the court. [ABSTRACT FROM AUTHOR]

In heme proteins, the canonical and reversed conformations result from the rotation of the heme group by 180° about the α,γ‐meso axis in the protein pocket. The coexistence of the two different heme orientations has been observed both in proteins reconstituted with hemin and in some native proteins. The reversal of the heme orientation can also change certain functional properties of heme proteins. Complementing the results from other experimental techniques, like circular dichroism and nuclear magnetic resonance, resonance Raman spectroscopy provides detailed information on the structure of the reversed heme. This allows one to elucidate the effects of the heme rotation on the vibrational spectra of the peripheral substituents, especially the vinyl groups. Furthermore, the combination of resonance Raman spectroscopy on single crystals and solution samples of heme proteins is proposed to be a sensitive tool to detect heme orientational disorder, even in the absence of structural data. [ABSTRACT FROM AUTHOR]

We consider a three-layer restricted Boltzmann machine, where the two visible layers (encoding for input and output, respectively) are made of binary neurons while the hidden layer is made of Gaussian neurons, and we show a formal equivalence with a Hopfield model. The machine architecture allows for different learning and operational modes: when all neurons are free to evolve we recover a standard Hopfield model whose size corresponds to the overall size of visible neurons; when input neurons are clamped we recover a Hopfield model, whose size corresponds to the size of the output layer, endowed with an external field as well as additional slow noise. The former stems from the signal provided by the input layer and tends to favour retrieval, the latter can be related to the statistical properties of the training set and tends to impair the retrieval performance of the network. We address this model by rigorous techniques, finding an explicit expression for its free-energy, whence a phase-diagram showing the performance of the system as parameters are tuned. [ABSTRACT FROM AUTHOR]

Providing public transportation with quality service is critical to attracting more passengers to the system. However, high-demand routes are prone to the so-called bus bunching--a tendency of buses to group as a consequence of variations in travel times and demands. Bus holding is applied to overcome this effect. In this study, we present a novel method for bus holding in which the control law is based only on the buses' position using a computationally efficient rolling horizon approach. The method uses similar inputs as linear control approaches while not increasing significantly the computational time. On the other hand, the method overcomes a key weakness of the linear control approach thanks to the explicit constraint handling that always ensures the control action effectiveness. Simulation experiments in a validation case and a model-specific for a bus rapid transit line in Curitiba, Brazil, showed a reduced holding time and improved resilience, delivering more than 20% reduction in delay time accounting for the on-board and station delays. [ABSTRACT FROM AUTHOR]

Objectives: EULAR recommendations do not suggest which biologic disease-modifying anti-rheumatic drug (bDMARD) should be preferred after failure of a first bDMARD in the treatment of rheumatoid arthritis (RA). In particular, few data are available regarding the effectiveness of a second-line bDMARD after failure of abatacept (ABA), tocilizumab (TCZ), and rituximab (RTX). The aim of this study was to analyze the retention rate of a second line with tumor necrosis factor inhibitors (TNFi) or other mechanisms of action (MoAs), after the failure of either RTX, TCZ, or ABA. Methods: Two hundred and seventy-eight RA patients from the Italian GISEA registry were included in the study. RTX was the first bDMARD in 18% of patients, ABA in 45.7%, and TCZ in 36.3%, while the second bDMARD was a TNFi (group 1) in 129 patients and an agent with a different MoA (group 2) in 149. Results: During a median follow-up of 22 months (IQR 68), 129 patients discontinued their treatment; patients of group 1 discontinued the treatment more frequently than patients of group 2 (p<0.001) with retention rates of 33.6±5.7% and 63.6±4.6% after 104 weeks for group 1 and group 2, respectively (p<0.001). At multivariate analysis, the mechanism of action was the only predictor for the maintenance in therapy. Conclusions: According to our data, ABA, RTX, and TCZ seem to maintain a good retention rate also when used as a second-line therapy, suggesting their use after the failure of a non-TNFi as first-line therapy. However, specifically designed studies are needed to evaluate the more appropriate therapeutic strategies in RA, according to the first-line drug, including new targeted synthetic DMARDs. Key Points • A large proportion of rheumatoid arthritis patients fail the first biologic DMARD. • Few data are available about the efficacy of biologic DMARD after the failure of a non-TNF inhibitor. • Abatacept, rituximab, or tocilizumab seem to maintain a good retention rate after the failure of a first-course therapy with a non-TNF inhibitor. [ABSTRACT FROM AUTHOR]

Objective: Most of the bodily functions are regulated by multiple interactions between the parasympathetic (PNS) and sympathetic (SNS) nervous system. In this study, we propose a novel framework to quantify the causal flow of information between PNS and SNS through the analysis of heart rate variability (HRV) and electrodermal activity (EDA) signals. Methods: Our method is based on a time-varying (TV) multivariate autoregressive model of EDA and HRV time-series and incorporates physiologically inspired assumptions by estimating the Directed Coherence in a specific frequency range. The statistical significance of the observed interactions is assessed by a bootstrap procedure purposely developed to infer causalities in the presence of both TV model coefficients and TV model residuals (i.e., heteroskedasticity). We tested our method on two different experiments designed to trigger a sympathetic response, i.e., a hand-grip task (HG) and a mental-computation task (MC). Results: Our results show a parasympathetic driven interaction in the resting state, which is consistent across different studies. The onset of the stressful stimulation triggers a cascade of events characterized by the presence or absence of the PNS-SNS interaction and changes in the directionality. Despite similarities between the results related to the two tasks, we reveal differences in the dynamics of the PNS-SNS interaction, which might reflect different regulatory mechanisms associated with different stressors. Conclusion: We estimate causal coupling between PNS and SNS through MVAR modeling of EDA and HRV time-series. Significance: Our results suggest promising future applicability to investigate more complex contexts such as affective and pathological scenarios. [ABSTRACT FROM AUTHOR]