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Abstract This article introduces and formalizes a novel stochastic method that combines inverse simulation with the theory of generalized Polynomial Chaos (gPC) to solve and study inverse problems under uncertainty in energy system design applications. The method is particularly relevant to design tasks where only a deterministic forward model of a physical system is available, in which a target design quantity is an input to the model that cannot be obtained directly, but can be quantified reversely via the outputs of the model. In this scenario, the proposed method offers an analytical and direct approach to invert such system models. The method puts emphasis on user-friendliness, as it enables its users to conduct the inverse simulation under uncertainty directly in the gPC domain by redefining basic algebra operations for computations. Moreover, the method incorporates an optimization-based approach to integrate supplementary constraints on stochastic quantities. This feature enables the solution of inverse problems bounding the statistical moments of stochastic system variables. The authors exemplify the application of the proposed method with proof-of-concept tests in energy system design, specifically performing uncertainty quantification and sensitivity analysis for a Multi-Energy System (MES). The findings demonstrate the high accuracy of the method as well as clear advantages over conventional sampling-based methods when dealing with a small number of stochastic variables in a system or model. However, the case studies also highlight the current limitations of the proposed method such as slow execution speed due to the optimization-based approach and the challenges associated with, for example, the curse of dimensionality in gPC.

Wood fuel from the agroforestry sector is one of the main strategies cited by the EU for reducing energetic dependance on foreign markets. Its sustainability, both economic and environmental, can be improved through the optimization of harvesting and chipping operations. This study was focused on the dynamic and energetic balance of the chipping phase carried out by a chipper operated by the power-take-off (PTO) of a medium-power tractor. Both machines were equipped with sensors for real-time monitoring of fuel consumption, PTO torque and speed, trunk diameter and working time during the comminution of 61 poplar trees grown in a medium rotation coppice system. The data analysis was carried out on the entire dataset (about 29,000 records) without considering their belonging to different trees. By means of proper data ordinations, it has been possible to define all the intervals in which the chipping stopped (e.g., between two trees) and to exclude them from the intervals of actual chipping. This has allowed forcomputation of operative and actual working time, as well as of the basic power required to operate the chipper and the power for actual chipping. Subsequently, the parameter values observed during actual chipping were related to the cutting diameters measured at the same instant. Subsequently, the dataset was divided according to seven diameter classes, and, for each class, the descriptive statistical indices of working time, work productivity, CO2 emissions, energy requirement and fuel consumption were calculated. Eventually, the correlation between the variations in trunk diameter and other parameters was verified both on the whole dataset and based on the class average values. The analysis made it possible to identify the conditions of greatest efficiency for the chipper. More generally, the method could help to increase the accuracy of measurements aimed at characterizing the performance of chippers from the point of view of dynamic energy requirements as well as in relation to different wood species.

Quantifying the effects of external climatic and anthropogenic stressors on aquatic ecosystems is an important task for scientific purposes and management progress in the field of water resources. In this study, we propose an innovative use of biotic communities as real-time indicators, which offers a promising solution to directly quantify the impact of these external stressors on the aquatic ecosystem health. Specifically, we investigated the influence of natural river floods on riverine biotic communities using freshwater mussels (FMs) as reliable biosensors. Using the valvometry technique, we monitored the valve gaping of FMs and analysed both the amplitude and frequency. The valve movement of the FMs was tracked by installing a magnet on one valve and a Hall effect sensor on the other valve. The magnetic field between the magnet and the sensor was recorded using an Arduino board, and its changes over time were normalised to give the opening percentage of the FMs (how open the mussels were). The recorded data were then analysed using continuous wavelet transform (CWT) analysis to study the time-dependent frequency of the signals. The experiments were carried out both in a laboratory flume and in the Paglia River (Italy). The laboratory experiments were conducted with FMs in two configurations: freely moving on the bed and immobilised on vertical rods. Testing of the immobilised configuration was necessary because the same configuration was used in the field in order to prevent FMs from packing against the downstream wall of the protection cage during floods or from breaking their connection wires. These experiments allowed us to verify that immobilised mussels show similar responses to abrupt changes in flow conditions as free mussels. Moreover, immobilised mussels produced more neat and interpretable signals than free-moving mussels due to the reduced number of features resulting from movement constraints. We then analysed the response of 13 immobilised mussels under real river conditions during a flood on 31 March 2022. The FMs in the field showed a rapid and significant change in valve gap frequency as the flood escalated, confirming the general behaviour observed in the laboratory in the presence of an abrupt increase in the flow. These results highlight the effectiveness of using FMs as biosensors for the timely detection of environmental stressors related to natural floods and emphasise the utility of CWT as a powerful signal-processing tool for the analysis of valvometry data. The study proposes the integration of FM valvometry and CWT for the development of operational real-time biological early-warning systems (BEWSs) with the aim of monitoring and protecting aquatic ecosystems. Future research should focus on extending the investigation of the responsiveness of FMs to specific stressors (e.g. turbidity, temperature, and chemicals) and on testing the applications of the proposed BEWSs to quantify the impact of both natural stressors (e.g. heat waves and droughts) and anthropogenic stressors (e.g. hydropeaking, reservoir flushing, and chemical contamination).

Abstract The EFSA Panel on Food Additives and Flavourings was requested to evaluate 14 flavouring substances assigned to the Flavouring Group Evaluation 80 (FGE.80), using the Procedure as outlined in the Commission Regulation (EC) No 1565/2000. Thirteen substances have already been considered in FGE.80 and its revision and in FGE.96 [FL‐no: 10.005, 10.024, 10.025, 10.050, 10.061, 10.069, 10.070, 10.072, 10.169, 13.009, 13.012, 13.161 and 16.055]. The remaining flavouring substance 3a,4,5,7a‐tetrahydro‐3,6‐dimethylbenzofuran‐2(3H)‐one [FL‐no: 10.057] has been cleared with respect to genotoxicity in FGE.217Rev3 and it is considered in this revision 2 of FGE.80. The substance [FL‐no: 10.057] was evaluated through a stepwise approach that integrates information on the structure–activity relationships, intake from current uses, threshold of toxicological concern (TTC) and available data on metabolism and toxicity. The Panel concluded that [FL‐no: 10.057] does not give rise to safety concerns at its levels of dietary intake, when estimated on the basis of the ‘Maximised Survey‐derived Daily Intake’ (MSDI) approach. Besides the safety assessment of the flavouring substance, the specifications for the material of commerce have also been considered and the information provided was complete for [FL‐no: 10.057]. However, for the flavouring substance [FL‐no: 10.057] in the present revision and for eight substances evaluated in previous revisions, the ‘modified Theoretical Added Maximum Daily Intakes’ (mTAMDIs) values are above the TTC for their structural class (III). For four substances previously evaluated in FGE.80Rev1 and in FGE.96, use levels are still needed to calculate the mTAMDI estimates. Therefore, in total for 13 flavouring substances, data on uses and use levels should be provided to finalise their safety evaluations. For [FL‐no: 10.050, 10.069 and 13.161], information on the composition of stereoisomeric mixtures is needed.

In this paper we present a scalable approach based on the latency-based linear multistep compound method to use graphic processing unit (GPU) to accelerate the power system simulations with electromagnetic transients.To balance between the computational load and accuracy, we modeled the power system using shifted frequency analysis. Then, to efficiently exploit the hardware, our computational approach is designed to utilize both data-parallel and task-parallel execution. In addition, a graph-based thread safety design is introduced to achieve high scalability in the paralleled component computations. Furthermore, our implementation introduces a translation layer for different heterogeneous computing frameworks during compile time, so that a wide range of GPU devices can be supported without losing performance. Finally, benchmark results show that our approach achieves faster-than-real-time capability for systems with hundreds to thousands of nodes.

Abstract The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of naringenin [FL‐no: 16.132] as a new flavouring substance, in accordance with Regulation (EC) No 1331/2008. No other substances with sufficient structural similarity have been identified in existing FGEs that could be used to support a read‐across approach. The information provided on the manufacturing process, the composition and the stability of [FL‐no: 16.132] was considered sufficient. From studies carried out with naringenin, the Panel concluded that there is no concern with respect to genotoxicity. The use of naringenin as a flavouring substance at added portions exposure technique (APET) exposure levels is unlikely to pose a risk for drug interaction. For the toxicological evaluation of naringenin, the Panel requested an extended one‐generation toxicity study on naringenin, in line with the requirements of the Procedure and to investigate the consequence of a possible endocrine‐disrupting activity. The Panel considered that changes in thymus weight, litter size, post‐implantation loss and a consistent reduced pup weight in the high‐dose F2 generation could not be dismissed and selected therefore, the mid‐dose of 1320 mg/kg body weight (bw) per day for the parental males as the no observed adverse effect level (NOAEL) of the study. The exposure estimates for [FL‐no: 16.132] (31,500 and 50,000 μg/person per day for children and adults, respectively) were above the threshold of toxicological of concern (TTC) for its structural class (III). Using the NOAEL of 1320 mg/kg bw per day at step A4 of the procedure, margins of exposure (MoE) of 1590 and 630 could be calculated for adults and children, respectively. Based on the calculated MoEs, the Panel concluded that the use of naringenin as a flavouring substance does not raise a safety concern.

Abstract The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of 2‐methyl‐1‐(2‐(5‐(p‐tolyl)‐1H‐imidazol‐2‐yl)piperidin‐1‐yl)butan‐1‐one [FL‐no: 16.134] as a new flavouring substance, in accordance with Regulation (EC) No 1331/2008. The substance has not been reported to occur naturally and is chemically synthesised. In food, it is intended to be used as a flavouring substance only in chewing gum. The chronic dietary exposure to [FL‐no: 16.134] was estimated to be 45 μg/person per day for a 60‐kg adult and 28.4 μg/person per day for a 15‐kg 3‐year‐old child. [FL‐no: 16.134] did not show genotoxicity in a bacterial reverse mutation test and an in vitro mammalian cell micronucleus assay. Based on the submitted toxicokinetic and metabolism data, it can be predicted that the flavouring substance is metabolised to innocuous products only. The Panel derived a lower confidence limit of the benchmark dose (BMDL) of 0.71 mg/kg bw per day for a 20% increase in the relative thyroid (including parathyroid) weight observed in a 90‐day toxicity study in rats. Based on this BMDL, adequate margins of exposure of 887 and 374 could be calculated for adults and children, respectively. The Panel concluded that there is no safety concern for [FL‐no: 16.134], when used as a flavouring substance at the estimated level of dietary exposure, based on the intended use and use levels as specified in Appendix B. The Panel further concluded that the combined exposure to [FL‐no: 16.134] from its use as a food flavouring substance and from its presence in toothpaste and mouthwash is also not of safety concern.

This article proposes the application of correlated Gaussian processes (Corr-GPs) for the recovery of missing intervals in power systems signals. Based on only local power system topology, the presented algorithm combines cross-channel information of the considered signals with a universal, nonparametric probabilistic machine learning regression to recover missing data. Starting from the theoretical background, the proposed approach is presented and contextualized in the framework of signal recovery for power systems. Then, by making use of real data collected from the Living Lab Energy Campus—a real-life laboratory established at Forschungszentrum Jülich—we demonstrate the use of the proposed approach for recovering distribution grid signals. We evaluate the performances of Corr-GP compared with those of other state-of-the-art techniques. In addition to outperformance in terms of recovery accuracy, it is explained when and how the accuracy of the reconstructed signal is independent of the missing interval length. Finally, detailed insights about key characteristics of the proposed approach that generate practical benefits for system operators are provided. A self-aware failing indication allowing system operators a direct evaluation of the recovered data and enabling further improvement of the proposed approach is presented, as well as recommendations for field implementation.

IntroductionIn autoimmune diseases, autoreactive B cells comprise only the 0.1-0.5% of total circulating B cells. However, current first-line treatments rely on non-specific and general suppression of the immune system, exposing patients to severe side effects. For this reason, identification of targeted therapies for autoimmune diseases is an unmet clinical need.MethodsHere, we designed a novel class of immunotherapeutic molecules, Bi-specific AutoAntigen-T cell Engagers (BiAATEs), as a potential approach for targeting the small subset of autoreactive B cells. To test this approach, we focused on a prototype autoimmune disease of the kidney, membranous nephropathy (MN), in which phospholipase A2 receptor (PLA2R) serves as primary nephritogenic antigen. Specifically, we developed a BiAATE consisting of the immunodominant Cysteine-Rich (CysR) domain of PLA2R and the single-chain variable fragment (scFv) of an antibody against the T cell antigen CD3, connected by a small flexible linker.ResultsBiAATE creates an immunological synapse between autoreactive B cells bearing an CysR-specific surface Ig+ and T cells. Ex vivo, the BiAATE successfully induced T cell-dependent depletion of PLA2R-specific B cells isolated form MN patients, sparing normal B cells. Systemic administration of BiAATE to mice transgenic for human CD3 reduced anti-PLA2R antibody levels following active immunization with PLA2R.DiscussionShould this approach be confirmed for other autoimmune diseases, BiAATEs could represent a promising off-the-shelf therapy for precision medicine in virtually all antibody-mediated autoimmune diseases for which the pathogenic autoantigen is known, leading to a paradigm shift in the treatment of these diseases.

Hirai et al. have developed a tool to assess the in vitro pressures of different compression devices. This tool has the advantage of being easy to use and finally inexpensive. The study of 7 bandages (Biflex 16, Urgo K2, Urgo K1, Coban 2, Biflex kit, Rosidal K and Rosidal Sys) on a Hirai leg allowed a precise analysis of the evolution of pressures and stiffnesses. Interface pressures were measured using the Picopress system and a 5 cm diameter probe. The difference between pre-stretch and stretch pressures in mmHg characterized stiffness. If the difference is greater than 10 mmHg, the bandage is considered stiff. These bandages were applied with a pressure of 45±2 mmHg at point B1. One hundred extension maneuvers were then performed. A decrease in mean pre-stretch pressures was noted more frequently for Rosidal K, Urgo K1 and Coban 2 than for the other bandages. Biflex 16 has a stiffness of less than 10 mmHg (p

Background Ultrasound-guided supra-inguinal fascia iliaca block (FIB) provides effective analgesia after total hip arthroplasty (THA) but is complicated by high rates of motor block. The erector spinae plane block (ESPB) is a promising motor-sparing technique. In this study, we tested the analgesic superiority of the FIB over ESPB and associated motor impairment. Methods In this randomized, observer-blinded clinical trial, patients scheduled for THA under spinal anesthesia were randomly assigned to preoperatively receive either the ultrasound-guided FIB or ESPB. The primary outcome was morphine consumption 24 h after surgery. The secondary outcomes were pain scores, assessment of sensory and motor block, incidence of postoperative nausea and vomiting and other complications, and development of chronic post-surgical pain. Results A total of 60 patients completed the study. No statistically significant differences in morphine consumption at 24 h (P = 0.676) or pain scores were seen at any time point. The FIB produced more reliable sensory block in the femoral nerve (P = 0.001) and lateral femoral cutaneous nerve (P = 0.018) distributions. However, quadriceps motor strength was better preserved in the ESPB group than in the FIB group (P = 0.002). No differences in hip adduction motor strength (P = 0.253), side effects, or incidence of chronic pain were seen between the groups. Conclusions ESPBs may be a promising alternative to FIBs for postoperative analgesia after THA. The ESPB and FIB offer similar opioid-sparing benefits in the first 24 h after surgery; however, ESPBs result in less quadriceps motor impairment.

An ideal therapeutic anti-SARS-CoV-2 antibody would resist viral escape1-3, have activity against diverse sarbecoviruses4-7, and be highly protective through viral neutralization8-11 and effector functions12,13. Understanding how these properties relate to each other and vary across epitopes would aid the development of therapeutic antibodies and guide vaccine design. Here we comprehensively characterize escape, breadth and potency across a panel of SARS-CoV-2 antibodies targeting the receptor-binding domain (RBD). Despite a trade-off between in vitro neutralization potency and breadth of sarbecovirus binding, we identify neutralizing antibodies with exceptional sarbecovirus breadth and a corresponding resistance to SARS-CoV-2 escape. One of these antibodies, S2H97, binds with high affinity across all sarbecovirus clades to a cryptic epitope and prophylactically protects hamsters from viral challenge. Antibodies that target the angiotensin-converting enzyme 2 (ACE2) receptor-binding motif (RBM) typically have poor breadth and are readily escaped by mutations despite high neutralization potency. Nevertheless, we also characterize a potent RBM antibody (S2E128) with breadth across sarbecoviruses related to SARS-CoV-2 and a high barrier to viral escape. These data highlight principles underlying variation in escape, breadth and potency among antibodies that target the RBD, and identify epitopes and features to prioritize for therapeutic development against the current and potential future pandemics.

Abstract The spike protein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can interact with endothelial cells. However, no studies demonstrated the direct effect of the spike protein subunit 1 (S1) in inducing lung vascular damage and the potential mechanisms contributing to lung injury. Here, we found that S1 injection in mice transgenic for human angiotensin converting enzyme 2 (ACE2) induced early loss of lung endothelial thromboresistance at 3 days, as revealed by thrombomodulin loss and von Willebrand factor (vWF) increase. In parallel, vascular and epithelial C3 deposits and enhanced C3a receptor (C3aR) expression were observed. These changes preceded diffuse alveolar damage and lung vascular fibrin(ogen)/platelets aggregates at 7 days, as well as inflammatory cell recruitment and fibrosis. Treatment with C3aR antagonist (C3aRa) inhibited lung C3 accumulation and C3a/C3aR activation, limiting vascular thrombo-inflammation and fibrosis. Our study demonstrates that S1 triggers vascular dysfunction and activates complement system, instrumental to lung thrombo-inflammatory injury. By extension, our data indicate C3aRa as a valuable therapeutic strategy to limit S1-dependent lung pathology.

In questo contributo si indagano alcuni tipi di costruzioni dell’italiano in cui i deittici prossimali e distali, a partire dalle funzioni originarie, hanno sviluppato delle ulteriori funzionalità pragmatico-discorsive. In particolare, i dimostrativi questo e quello all’interno di alcune specifiche configurazioni sintattico-discorsive possono assumere funzione valutativa e intensificare o mitigare gli attributi qualitativi del referente, facendo leva su conoscenze realmente condivise dai parlanti o presupposte come tali. Tramite l’analisi di dati autentici estratti dal webcorpus itTenTen20 e adottando un approccio misto (corpus-driven e corpus-based), ci proponiamo di descrivere i processi inferenziali che permettono all’interlocutore di attivare la lettura valutativa dei deittici in due particolari costruzioni: [quel N lì] e [(N1) non è (che sia) questo N2]. “We are not these experts”. Evaluative uses of proximal and distal deictics In this contribution, we intend to investigate two Italian constructions in which proximal and distal deictics, starting from their original functions, have developed additional discursive-pragmatic functions. In particular, the demonstratives questo ‘this’ and quello ‘that’ within some specific syntactic and discursive configurations can take on evaluative functions. They can intensify or mitigate the qualitative attributes of the referent, drawing on the knowledge shared by the speakers or presupposed as such. Through the analysis of authentic data from the itTenTen20 webcorpus and adopting a mixed approach (both corpus-driven and corpus-based), we aim to describe the inferential processes that enable the interlocutor to activate the evaluative reading of deictics in two specific constructions: [quel N lì] and [(N1) non è (che sia) questo N2].

Abstract The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of the smoke flavouring Primary Product SmokEz Enviro‐23 (SF‐006), for which a renewal application was submitted in accordance with Article 12(1) of Regulation (EC) No 2065/2003. This opinion refers to the assessment of data submitted on chemical characterisation, dietary exposure and genotoxicity of the Primary Product. SmokEz Enviro‐23 is obtained by pyrolysis of oak, maple, hickory, ash, birch, beech and cherry woods. Given the limitations of the quantification approach employed by the applicant, the Panel could not judge whether the applied methods meet the legal quality criterion that at least 80% of the volatile fraction shall be identified and quantified. At the maximum proposed use levels, dietary exposure estimates calculated with DietEx ranged from 0.01 to 3.2 mg/kg body weight (bw) per day at the mean and from no dietary exposure to 9.5 mg/kg bw per day at the 95th percentile. The Panel concluded that four components in the Primary Product raise a potential concern for genotoxicity. In addition, a potential concern for genotoxicity was identified for the unidentified part of the mixture. The Primary Product contains furan‐2(5H)‐one and benzene‐1,2‐diol, for which a concern for genotoxicity was identified in vivo upon oral administration. Considering that the exposure estimates for these two components are above the threshold of toxicological concern (TTC) of 0.0025 μg/kg bw per day for DNA‐reactive mutagens and/or carcinogens, the Panel concluded that the Primary Product raises concern with respect to genotoxicity.

Abstract The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of the smoke flavouring Primary Product SmoKEz C‐10 (SF‐005), for which a renewal application was submitted in accordance with Article 12(1) of Regulation (EC) No 2065/2003. This opinion refers to the assessment of data submitted on chemical characterisation, dietary exposure and genotoxicity of the Primary Product. SmoKEz C‐10 is obtained by pyrolysis of maple, oak, hickory, ash, birch, beech and cherry woods. Given the limitations of the quantification approach employed by the applicant, the Panel could not judge whether the applied methods meet the legal quality criterion that at least 80% of the volatile fraction shall be identified and quantified. At the maximum proposed use levels, dietary exposure estimates calculated with DietEx ranged from 0.01 to 5.1 mg/kg body weight (bw) per day at the mean and from no dietary exposure to 18.1 mg/kg bw per day at the 95th percentile. The Panel concluded that five components in the Primary Product raise a potential concern for genotoxicity. In addition, a potential concern for genotoxicity was identified for the unidentified part of the mixture. The Primary Product contains furan‐2(5H)‐one and benzene‐1,2‐diol, for which a concern for genotoxicity was identified in vivo upon oral administration. Considering that the exposure estimates for these two components are above the threshold of toxicological concern (TTC) of 0.0025 μg/kg bw per day for DNA‐reactive mutagens and/or carcinogens, the Panel concluded that the Primary Product raises concern with respect to genotoxicity.

Abstract The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of the smoke flavouring Primary Product Smoke Concentrate 809045 (SF‐003), for which a renewal application was submitted in accordance with Article 12(1) of Regulation (EC) No 2065/2003. This opinion refers to the assessment of data submitted on chemical characterisation, dietary exposure and genotoxicity of the Primary Product. Product Smoke Concentrate 809045 is obtained by pyrolysis of beech wood. The Panel concluded that the compositional data provided on the Primary Product are adequate. At the maximum proposed use levels, dietary exposure estimates calculated with DietEx ranged from 0.1 to 1.5 mg/kg body weight (bw) per day at the mean and from 0.2 to 5.2 mg/kg bw per day at the 95th percentile. The Panel concluded that eleven components in the Primary Product raise a potential concern for genotoxicity. In addition, a potential concern for genotoxicity was identified for the unidentified part of the mixture. The Primary Product contains furan‐2(5H)‐one and benzene‐1,2‐diol, for which a concern for genotoxicity was identified in vivo upon oral administration. Considering that the exposure estimates for these two components are above the threshold of toxicological concern (TTC) of 0.0025 μg/kg bw per day for DNA‐reactive mutagens and/or carcinogens, the Panel concluded that the Primary Product raises concern with respect to genotoxicity.

Abstract The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of the smoke flavouring Primary Product proFagus Smoke R714 (SF‐001), for which a renewal application was submitted in accordance with Article 12(1) of Regulation (EC) No 2065/2003. This opinion refers to the assessment of data submitted on chemical characterisation, dietary exposure and genotoxicity of the Primary Product. ProFagus Smoke R714 is obtained by pyrolysis of beech and oak woods as main source materials. Based on the compositional data, the Panel noted that the identified and quantified proportion of the solvent‐free fraction amounts to 39 weight (wt)%, thus the applied method does not meet the legal quality criterion that at least 50% of the solvent‐free fraction shall be identified and quantified. At the maximum proposed use levels, dietary exposure estimates calculated with DietEx ranged from 0.7 to 10.9 mg/kg body weight (bw) per day at the mean and from 2.2 to 42.5 mg/kg bw per day at the 95th percentile. The Panel concluded that three components in the Primary Product raise a potential concern for genotoxicity. In addition, a potential concern for genotoxicity was identified for the unidentified part of the mixture. The Primary Product contains furan‐2(5H)‐one, for which a concern for genotoxicity was identified in vivo upon oral administration. Considering that the exposure estimates for this component are above the threshold of toxicological concern (TTC) of 0.0025 μg/kg bw per day for DNA‐reactive mutagens and/or carcinogens, the Panel concluded that the Primary Product raises concern with respect to genotoxicity.

Abstract The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of the smoke flavouring Primary Product Fumokomp (SF‐009), for which a renewal application was submitted in accordance with Article 12(1) of Regulation (EC) No 2065/2003 (in the renewal application the Primary Product is reported as ‘Fumokomp Conc.’). This opinion refers to an assessment of data submitted on chemical characterisation, dietary exposure and genotoxicity of the Primary Product. Fumokomp Conc. is produced by pyrolysis of beech and hornbeam woods. Gas chromatography–mass spectrometry (GC–MS) was applied for both identification and quantification of the volatile constituents of the Primary Product. Given the limitations of the method, the Panel cannot judge with confidence whether the applied method meets the legal quality criterion that at least 80% of the volatile fraction shall be identified and quantified. Moreover, the Panel concluded that the absence of furan‐2(5H)‐one from the Primary Product was not convincingly demonstrated. At the maximum proposed use levels, dietary exposure estimates calculated with FAIM ranged from 0.04 to 0.9 mg/kg body weight (bw) per day at the mean and from 0.1 to 1.5 mg/kg bw per day at the 95th percentile. The information available on the 32 identified components of the Primary Product, although limited, did not indicate a concern for genotoxicity for any of these substances. However, whole mixture testing in an in vitro mouse lymphoma assay gave positive results which would require an adequate in vivo follow‐up study. In addition, the potential for aneugenicity of the Primary Product has not been adequately investigated. Accordingly, the potential safety concern for genotoxicity of the Primary Product cannot be ruled out.

Abstract The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of the smoke flavouring Primary Product Zesti Smoke Code 10 (SF‐002), for which a renewal application was submitted in accordance with Article 12(1) of Regulation (EC) No 2065/2003. This opinion refers to the assessment of data submitted on chemical characterisation, dietary exposure and genotoxicity of the Primary Product. Zesti Smoke Code 10 is obtained by pyrolysis of hickory and oak woods. Given the limitations of the quantification approach employed by the applicant, the Panel could not judge whether the applied methods meet the legal quality criterion that at least 80% of the volatile fraction shall be identified and quantified. At the maximum proposed use levels, dietary exposure estimates calculated with DietEx ranged from 0.02 to 4.6 mg/kg body weight (bw) per day at the mean and from no dietary exposure to 13.0 mg/kg bw per day at the 95th percentile. The Panel concluded that four components in the Primary Product raise a potential concern for genotoxicity. In addition, a potential concern for genotoxicity was identified for the unidentified part of the mixture. The Primary Product contains furan‐2(5H)‐one and benzene‐1,2‐diol, for which a concern for genotoxicity was identified in vivo upon oral administration. Considering that the exposure estimates for these two components are above the threshold of toxicological concern (TTC) of 0.0025 μg/kg bw per day for DNA‐reactive mutagens and/or carcinogens, the Panel concluded that the Primary Product raises concern with respect to genotoxicity.

Abstract The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of the smoke flavouring Primary Product Scansmoke SEF7525 (SF‐004), for which a renewal application was submitted in accordance with Article 12(1) of Regulation (EC) No 2065/2003. This opinion refers to the assessment of data submitted on chemical characterisation, dietary exposure and genotoxicity of the Primary Product. Scansmoke SEF7525 is obtained from a tar produced from a mixture of red oak, white oak, maple, beech and hickory. Based on the compositional data, the Panel noted that the identified and quantified proportion of the solvent‐free fraction amounts to 32.6 weight (wt)%, thus the applied method does not meet the legal quality criterion that at least 50% of the solvent‐free fraction shall be identified and quantified. At the maximum proposed use levels, dietary exposure estimates calculated with Food Additive Intake Model (FAIM) ranged from 0.6 to 3.8 mg/kg body weight (bw) per day at the mean and from 1.1 to 10.1 mg/kg bw per day at the 95th percentile. Based on the available information on genotoxicity on 44 identified components, the Panel concluded that two substances in the Primary Product, styrene and benzofuran, raise a potential concern for genotoxicity. In addition, a potential concern for genotoxicity was identified for the unidentified part of the mixture. Considering that the exposure estimates for styrene and benzofuran are above the threshold of toxicological concern (TTC) value of 0.0025 kg/kg bw per day for DNA‐reactive mutagens and/or carcinogens and since further data are needed to clarify their potential genotoxicity, the Panel concluded that the potential safety concern for genotoxicity of the Primary Product cannot be ruled out.

During the second half of the 20th century, despite the flourishing of Spinoza scholarship (particularly in the French-speaking world) references to Spinoza seem to be rather infrequent in the famous Catholic journal Revue philosophique de Louvain. On closer inspection, however, it is possible to trace a precise attitude of the editors of the Belgian journal, according to which the historiographic representation of the Dutch philosopher constitutes the test-bed of a more general cultural strategy. In contact with phenomenology, anti-Cartesianism, the biological sciences, psychoanalysis and Marxism, the Spinoza of the Catholic journal becomes an entirely new and unusual figure, with respect to the image still prevalent in Spinoza studies today.

Summary: Large GWAS indicated that genetic factors influence the response to SARS-CoV-2. However, sex, age, concomitant diseases, differences in ancestry, and uneven exposure to the virus impacted the interpretation of data. We aimed to perform a GWAS of COVID-19 outcome in a homogeneous population who experienced a high exposure to the virus and with a known infection status. We recruited inhabitants of Bergamo province—that in spring 2020 was the epicenter of the SARS-Cov-2 pandemic in Europe—via an online questionnaire followed by personal interviews. Cases and controls were matched by age, sex and risk factors. We genotyped 1195 individuals and replicated the association at the 3p21.31 locus with severity, but with a stronger effect size that further increased in gravely ill patients. Transcriptome-wide association study highlighted eQTLs for LZTFL1 and CCR9. We also identified 17 loci not previously reported, suggestive for an association with either COVID-19 severity or susceptibility.

All’inizio del Settecento, fra i temi sui quali si concentrano i dibattiti sul nuovo modello di ragione proposto dall’autore dell’Ethica vi è quello della nuova determinazione e collocazione teorica e morale di due categorie che rappresentavano un dittico consueto nelle controversie religiose, filosofico-morali e politiche: ‘ateismo’ e ‘superstizione’. L’articolo ricostruisce l’evoluzione dell’immagine del filosofo olandese in alcuni dibattiti accademici di inizio Settecento analizzando in particolare le nozioni di ‘ateismo’ e ‘superstizione’ individuate e messe in campo dai critici, e l’equilibrio fra religio e ratio che queste definiscono rispetto allo ‘spinozismo’, polemicamente assunto come emblema ed esito della moderna ragione filosofica e dei suoi eccessi.

Abstract Background Insecticide resistance is a key barrier to long-term malaria control, and it may be exacerbated by poor agricultural pesticide use. Current practices, however, do not link public health and agricultural pesticide use. This study investigated the perspectives of farmers and other stakeholders regarding the integration of agricultural and public health measures to address resistance. Additionally, the feasibility of participatory workshops to increase the farmers’ understanding and participation in pesticide stewardship was assessed. Methods Four themes were investigated: pesticide awareness, practices, and opinions of; insecticide resistance in malaria vectors; the effectiveness of current malaria prevention tools; and the links between agricultural and public health pesticide usage. Participatory workshops and field training were held with entomologists, farmers, and agricultural specialists, focusing on agro-ecosystem practices related to pest control; and local farmers were involved in live-testing for insecticides resistance of local Anopheles mosquitoes. Results Most farmers (94%) considered pesticides effective, and nearly half of them (n = 198, 46.4%) could identify and name crop pests and diseases, mostly using local names. Three quarters were unaware of mosquito larvae in their fields, and only 7% considered their fields as potential sources of mosquitoes. Two thirds were uninformed of any effects that agricultural pesticides may have on mosquitoes, and three quarters had never heard of resistance in malaria mosquitoes. Experts from various sectors acknowledged that agricultural pesticides might impact malaria control through increasing resistance. They did, however, emphasize the importance of crop protection and advocated for the use of pesticides sparingly and non-chemical approaches. Farmers learnt how to discriminate between malaria vectors and non-vectors, identify agricultural pests and diseases, choose and use pesticides effectively, and conduct resistance tests during the participatory workshops. Conclusion This study emphasizes the significance of enhancing subsistence farmers’ awareness of mosquito ecology as well as merging public health and agricultural pest management measures. Participatory techniques have the potential to raise stakeholder awareness and engagement, resulting in more effective resistance management.

Beyond total kidney and cyst volume, non-cystic tissue plays an important role in autosomal dominant polycystic kidney disease (ADPKD) progression. Recent advancements in magnetic resonance imaging (MRI) offer the possibility to study kidney microstructure and function, besides anatomy. In particular, Diffusion Weighted Imaging (DWI), an MRI technique sensitive to water molecule motion (diffusion) in biological tissues, allows to investigate microstructure. This study, recently published in the European Radiology scientific journal, proposes and preliminary validates a novel method to segment cystic and non-cystic volume on DWI scans from ADPKD patients. The study also provides evidence of DWI potential in characterising non-cystic kidney tissue, denoted by higher diffusion and lower perfusion than healthy tissue, in line with its fibrotic nature and the likely presence of microcysts. Overall, this study provides evidence in support of DWI potential in ADPKD. DWI could complement existing biomarkers for noninvasively staging, monitoring, and predicting ADPKD progression and evaluating the impact of novel therapies, possibly targeting damaged non-cystic tissue besides cyst expansion.

The Middle and Upper Jurassic sequence near Foza (Asiago plateau; Venetian Alps) is characterized by important hiatuses. The relevant deposits are furthermore often found as sedimentary dikes, filling up fractures in the underlying carbonatic platform of the Calcari Grigi, Middle Liassic in age in the uppermost levels. The normal Middle and Upper Jurassic sequence includes, aver the Calcari Grigi the following formations: Lower Rosso Ammonitico Veronese and "Lumachella a Posidonia alpina", both Middle Ju­rassic in age; "Scisti ad Aptici", Upper Rosso Ammonitico Veronese and the basal part of the "Biancone", Upper Jurassic in age. In the Foza area the stratigraphic sequence changes quite rapidly in very short distances, with hiatuses involving one or more of the above mentioned formations. The presence of these hiatuses and of sedimentary dikes is in agreement with the location of the studied area near the edge of the "Trento plateau" during the Jurassic. A fossil assemblage was collected from a sedimentary dike near Lazzaretti of Foza. It consists of Brachiopods, Belemnites, Bivalves and Crinoid remains. Brachiopods are prevailing both in specimens and species number; among them 6 species, even if generally poorly preserved have been determined and described.