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Automated Market Makers (AMMs) are an integral component of the decentralized finance (DeFi) ecosystem, as they allow users to exchange crypto-assets without the need for trusted authorities or external price oracles. Although these protocols are based on relatively simple mechanisms, e.g., to algorithmically determine the exchange rate between crypto-assets, they give rise to complex economic behaviours. This complexity is witnessed by the proliferation of models that study their structural and economic properties. Currently, most of theoretical results obtained on these models are supported by pen-and-paper proofs. This work proposes a formalization of constant-product AMMs in the Lean 4 Theorem Prover. To demonstrate the utility of our model, we provide mechanized proofs of key economic properties like arbitrage, that at the best of our knowledge have only been proved by pen-and-paper before.

We conducted a retrospective/prospective worldwide study on patients with neuroendocrine neoplasms (NENs) and a molecularly proven SARS-CoV-2 positivity. Preliminary results regarding 85 patients of the INTENSIVE study have been published in 2021. Now we are reporting the 2-year analysis. Here, we are reporting data from consecutive patients enrolled between 1 June 2020, and 31 May 2022. Among the 118 contacted centers, 25 were active to enroll and 19 actively recruiting at the time of data cut-off for a total of 280 patients enrolled. SARS-CoV-2 positivity occurred in 47.5% of patients in 2020, 35.1% in 2021, and 17.4% in 2022. The median age for COVID-19 diagnosis was 60 years. Well-differentiated tumors, non-functioning, metastatic stage, and gastroenteropancreatic (GEP) primary sites represented most of the NENs. COVID-19-related pneumonia occurred in 22.8% of the total, with 61.3% of them requiring hospitalization; 11 patients (3.9%) needed sub-intensive or intensive care unit therapies and 14 patients died (5%), in 11 cases (3.9%) directly related to COVID-19. Diabetes mellitus and age at COVID-19 diagnosis > 70 years were significantly associated with COVID-19 mortality, whereas thoracic primary site with COVID-19 morbidity. A significant decrease in both hospitalization and pneumonia occurred in 2022 vs 2020. In our largest series of NEN patients with COVID-19, the NEN population is similar to the general population of patients with NEN regardless of COVID-19. However, older age, non-GEP primary sites and diabetes mellitus should be carefully considered for increased COVID-19 morbidity and mortality. Relevant information could be derived by integrating our results with NENs patients included in other cancer patients with COVID-19 registries.

Belonging to a group is a natural need for human beings. Being left out and rejected represents a negative event, which can cause discomfort and stress to the excluded person and other members. Social robots have been shown to have the potential to be optimal tools for studying influence in group interactions, providing valuable insights into how human group dynamics can be modeled, replicated, and leveraged. In this work, we aim to study the effect of being excluded by a social robot in a teenagers-robot interaction. We propose a conversational turn-taking game, inspired by the Cyberball paradigm and rooted in social exclusion mechanisms, to explore how the humanoid robot iCub can affect group dynamics by excluding one of the group members. Preliminary results show that the included player tries to re-engage with the one excluded by the robot. We interpret this dynamic as an included player's tentative to compensate for the exclusion and reestablish a balance, in line with findings in human-human interaction research. Furthermore, the paradigm we developed seems a suitable tool for researching social influence in different Human-Robot Interaction contexts.

Belonging to a group is a natural need for human beings. Being left out and rejected represents a negative event, which can cause discomfort and stress to the excluded person and other members. Social robots have been shown to have the potential to be optimal tools for studying influence in group interactions, providing valuable insights into how human group dynamics can be modeled, replicated, and leveraged. In this work, we aim to study the effect of being excluded by a social robot in a teenagers-robot interaction. We propose a conversational turn-taking game, inspired by the Cyberball paradigm and rooted in social exclusion mechanisms, to explore how the humanoid robot iCub can affect group dynamics by excluding one of the group members. Preliminary results show that the included player tries to re-engage with the one excluded by the robot. We interpret this dynamic as an included player's tentative to compensate for the exclusion and reestablish a balance, in line with findings in human-human interaction research. Furthermore, the paradigm we developed seems a suitable tool for researching social influence in different Human-Robot Interaction contexts.

RECIST 1.1 criteria are commonly used with computed tomography (CT) to evaluate the efficacy of systemic treatments in patients with neuroendocrine tumors (NETs) and liver metastases (LMs), but their relevance is questioned in this setting. We aimed to explore alternative criteria using different numbers of measured LMs and thresholds of size and density variation. We retrospectively studied patients with advanced pancreatic or small intestine NETs with LMs, treated with systemic treatment in the first-and/or second-line, without early progression, in 14 European expert centers. We compared time to treatment failure (TTF) between responders and non-responders according to various criteria defined by 0%, 10%, 20% or 30% decrease in the sum of LM size, and/or by 10%, 15% or 20% decrease in LM density, measured on two, three or five LMs, on baseline (≤1 month before treatment initiation) and first revaluation (≤6 months) contrast-enhanced CT scans. Multivariable Cox proportional hazard models were performed to adjust the association between response criteria and TTF on prognostic factors. We included 129 systemic treatments (long-acting somatostatin analogs 41.9%, chemotherapy 26.4%, targeted therapies 31.8%), administered as first-line (53.5%) or second-line therapies (46.5%) in 91 patients. A decrease ≥10% in the size of three LMs was the response criterion that best predicted prolonged TTF, with significance at multivariable analysis (HR 1.90; 95% CI: 1.06–3.40; p =.03). Conversely, response defined by RECIST 1.1 did not predict prolonged TTF (p =.91), and neither did criteria based on changes in LM density. A ≥10% decrease in size of three LMs could be a more clinically relevant criterion than the current 30% threshold utilized by RECIST 1.1 for the evaluation of treatment efficacy in patients with advanced NETs. Its implementation in clinical trials is mandatory for prospective validation. Criteria based on changes in LM density were not predictive of treatment

Belonging to a group is a natural need for human beings. Being left out and rejected represents a negative event, which can cause discomfort and stress to the excluded person and other members. Social robots have been shown to have the potential to be optimal tools for studying influence in group interactions, providing valuable insights into how human group dynamics can be modeled, replicated, and leveraged. In this work, we aim to study the effect of being excluded by a social robot in a teenagers-robot interaction. We propose a conversational turn-taking game, inspired by the Cyberball paradigm and rooted in social exclusion mechanisms, to explore how the humanoid robot iCub can affect group dynamics by excluding one of the group members. Preliminary results show that the included player tries to re-engage with the one excluded by the robot. We interpret this dynamic as an included player's tentative to compensate for the exclusion and reestablish a balance, in line with findings in human-human interaction research. Furthermore, the paradigm we developed seems a suitable tool for researching social influence in different Human-Robot Interaction contexts.

Objective(s): Examine the effect of resistance and power training with walking in four directions on the N-terminal peptide of type III procollagen (P3NP), the C-terminal agrin fragment (CAF), the lower body muscle strength and motor function in elderly people. Materials and Methods: Thirty-one elderly men were selected and divided into three groups: control group (C); resistance training (RT) group, and power training (PT) group. RT was performed with 8–10 repetitions during 20–35 seconds of exercise and PT with 8–10 repetitions during 10–13 seconds of exercise. The exercise to which subjects were exposed to, in both resistance and power training groups, consisted in walking in four directions for 12 weeks (two sessions per week). Body mass index (BMI), functional tests, and lower body strength were also measured. The serum levels of P3NP and CAF were evaluated in all groups. Results: Lower body strength (leg press, plantar ankle flexion, knee extension, leg curl) and motor function (chair stand test, timed up and go, 6-minute walking), improved following the exercise, while no effect was found concerning the serum levels of P3NP and CAF. Conclusions: An increase in motor function and lower body strength was observed in both types of exercise programmes discussed in this paper, although the exercise should be done rapidly for a better result.

Background: Previous studies on oxaliplatin and fluoropyrimidines as adjuvant therapy in older patients with stage III colon cancer (CC) produced conflicting results. Patients and methods: We assessed the impact of age on time to tumour recurrence (TTR), disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) in 2360 patients with stage III CC (1667 aged <70 years and 693 ≥ 70 years) randomised to receive 3 or 6 months of FOLFOX or CAPOX within the frame of the phase III, TOSCA study. Results: Older patients compared with younger ones presented more frequently an Eastern Cooperative Oncology Group performance status equal to 1 (10.5% vs 3.3%, p < 0.001), a greater number of right-sided tumours (40.9% vs 26.6%, p < 0.001), and were at higher clinical risk (37.2% vs 33.2%, p = 0.062). The treatments were almost identical in the two cohorts (p = 0.965). We found a greater proportion of dose reductions (46.7% vs 41.4%, p = 0.018), treatment interruptions (26.1% vs 19.3%, p < 0.001) and a higher proportion of recurrences (24.2% vs 20.3%, p = 0.033) in the older patients. The multivariable analysis of the TTR did not indicate a statistically significant effect of age (hazard ratio [HR]: 1.19; 95% confidence interval [CI]: 0.98–1.44; p = 0.082). The HR comparing older with younger patients was 1.34 (95% CI: 1.12–1.59; p = 0.001) for DFS, 1.58 (95% CI: 1.26–1.99; p < 0.001) for OS, and 1.28 (95% CI: 0.96–1.70; p = 0.089) for CSS. Conclusions: Worse prognostic factors and reduced treatment compliance have a negative impact on the efficacy of oxaliplatin-based adjuvant therapy in older patients.

Background: Patients with sporadic neuroendocrine neoplasms may exhibit a higher risk of a second primary tumor than the general population. Aim: This study aimed to analyze the occurrence of second primary malignancies. Methods: A retrospective cohort of 2757 patients with sporadic lung and gastro-entero-pancreatic neuroendocrine neoplasms, managed at eight Italian tertiary referral Centers, was included. Results: Between 2000 and 2019, a second primary malignancy was observed in 271 (9.8%) neuroendocrine neoplasms patients with 32 developing a third tumor. There were 135 (49.8%) females and the median age was 64 years. The most frequent locations of the second tumors were breast (18.8%), prostate (12.5%), colon (9.6%), blood tumors (8.5%), and lung (7.7%). The second primary tumor was synchronous in 19.2% of cases, metachronous in 43.2%, and previous in 37.6%. As concerned the neuroendocrine neoplasms, the 5- and 10-year survival rates were 87.8% and 74.4%, respectively. PFS for patients with a second primary malignancy was shorter than for patients without a second primary malignancy. Death was mainly related to neuroendocrine neoplasms. Conclusion: In NEN patients the prevalence of second primary malignancies was not negligible, suggesting a possible neoplastic susceptibility. Overall survival was not affected by the occurrence of a second primary malignancy.

Marine heat waves (MHWs), prolonged discrete anomalously warm water events, have been increasing significantly in duration, intensity and frequency all over the world, and have been associated with a variety of impacts including alteration of ecosystem structure and function. This study assessed the effects of current and future MHWs on the Mediterranean seagrass Posidonia oceanica performance, also testing the importance of the thermal environment where the plant lives. The effects of current MHWs were studied through a mensurative experiment in a cold and in a warm site (West and North-West Sardinia, Italy, respectively). Future MHWs effects were tested through a manipulative experiment using P. oceanica shoots collected from the cold and warm sites and transplanted in a common garden in front of a power plant (North-West Sardinia): here plants were exposed to heat longer in duration and stronger in intensity than the natural MHWs of the last 20 years, resembling the future scenario. Morphological (total # of leaves, maximum leaf length, and percentage of total necrotic leaf length per shoot) and biochemical variables (leaf proteins, carbohydrates, and lipids) were considered. Plants had similar sublethal responses in both the experiments for most of the variables, revealing that current and future MHWs had similar effect types, but different in magnitude depending on the intensity of the waves: in general, the number of leaves, the maximum leaf length and lipid content decreased, while the leaf necrosis and carbohydrates increased. However, also the origin of the plants affected the results, corroborating the hypothesis that the thermal context the plants live affects their tolerance to the heat. Overall, this study provided evidence about the importance of biochemical variations, such as carbohydrate and lipid levels, as potentially good indicators of seagrass heat stress.

This study presents novel strategies to investigate the mutual influence of trust and group dynamics in children-robot interaction. We implemented a game-like experimental activity with the humanoid robot iCub and designed a questionnaire to assess how the children perceived the interaction. We also aim to verify if the sensors, setups, and tasks are suitable for studying such aspects. The questionnaires' results demonstrate that youths perceive iCub as a friend and, typically, in a positive way. Other preliminary results suggest that, generally, children trusted iCub during the activity and, after its mistakes, they tried to reassure it with sentences such as: "Don't worry iCub, we forgive you". Furthermore, trust towards the robot in group cognitive activity appears to change according to gender: after two consecutive mistakes by the robot, girls tended to trust iCub more than boys. Finally, no significant difference has been evidenced between different age groups across points computed from the game and the self-reported scales. The tool we proposed is suitable for studying trust in human-robot interaction (HRI) across different ages and seems appropriate to understand the mechanism of trust in group interactions., Comment: in SCRITA Workshop Proceedings (arXiv:2208.11090) held in conjunction with 31st IEEE International Conference on Robot & Human Interactive Communication, 29/08 - 02/09 2022, Naples (Italy). Francesca Cocchella and Giulia Pusceddu contributed equally to this work, hence they share the first name

Although considerable research progress on the effects of anthropogenic disturbance in the deep sea has been made in recent years, our understanding of these impacts at community level remains limited. Here, we studied deep-sea assemblages of Sicily (Mediterranean Sea) subject to different intensities of benthic trawling using environmental DNA (eDNA) metabarcoding and taxonomic identification of meiofauna communities. Firstly, eDNA metabarcoding data did not detect trawling impacts using alpha diversity whereas meiofauna data detected a significant effect of trawling. Secondly, both eDNA and meiofauna data detected significantly different communities across distinct levels of trawling intensity when we examined beta diversity. Taxonomic assignment of the eDNA data revealed that Bryozoa was present only at untrawled sites, highlighting their vulnerability to trawling. Our results provide evidence for community-wide impacts of trawling, with different trawling intensities leading to distinct deep-sea communities. Finally, we highlight the need for further studies to unravel understudied deep-sea biodiversity.

Although considerable research progress on the effects of anthropogenic disturbance in the deep sea has been made in recent years, our understanding of these impacts at community level remains limited. Here, we studied deep-sea assemblages of Sicily (Mediterranean Sea) subject to different intensities of benthic trawling using environmental DNA (eDNA) metabarcoding and taxonomic identification of meiofauna communities. Firstly, eDNA metabarcoding data did not detect trawling impacts using alpha diversity whereas meiofauna data detected a significant effect of trawling. Secondly, both eDNA and meiofauna data detected significantly different communities across distinct levels of trawling intensity when we examined beta diversity. Taxonomic assignment of the eDNA data revealed that Bryozoa was present only at untrawled sites, highlighting their vulnerability to trawling. Our results provide evidence for community-wide impacts of trawling, with different trawling intensities leading to distinct deep-sea communities. Finally, we highlight the need for further studies to unravel understudied deep-sea biodiversity.

Although considerable research progress on the effects of anthropogenic disturbance in the deep sea has been made in recent years, our understanding of these impacts at community level remains limited. Here, we studied deep-sea assemblages of Sicily (Mediterranean Sea) subject to different intensities of benthic trawling using environmental DNA (eDNA) metabarcoding and taxonomic identification of meiofauna communities. Firstly, eDNA metabarcoding data did not detect trawling impacts using alpha diversity whereas meiofauna data detected a significant effect of trawling. Secondly, both eDNA and meiofauna data detected significantly different communities across distinct levels of trawling intensity when we examined beta diversity. Taxonomic assignment of the eDNA data revealed that Bryozoa was present only at untrawled sites, highlighting their vulnerability to trawling. Our results provide evidence for community-wide impacts of trawling, with different trawling intensities leading to distinct deep-sea communities. Finally, we highlight the need for further studies to unravel understudied deep-sea biodiversity.

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

KEY POINTS:•Nucleotide binding oligomerization domain (Nod)-like receptors regulate cognition, anxiety and hypothalamic-pituitary-adrenal axis activation. •Nod-like receptors regulate central and peripheral serotonergic biology. •Nod-like receptors are important for maintenance of gastrointestinal physiology. •Intestinal epithelial cell expression of Nod1 receptors regulate behaviour. ABSTRACT:Gut-brain axis signalling is critical for maintaining health and homeostasis. Stressful life events can impact gut-brain signalling, leading to altered mood, cognition and intestinal dysfunction. In the present study, we identified nucleotide binding oligomerization domain (Nod)-like receptors (NLR), Nod1 and Nod2, as novel regulators for gut-brain signalling. NLR are innate immune pattern recognition receptors expressed in the gut and brain, and are important in the regulation of gastrointestinal physiology. We found that mice deficient in both Nod1 and Nod2 (NodDKO) demonstrate signs of stress-induced anxiety, cognitive impairment and depression in the context of a hyperactive hypothalamic-pituitary-adrenal axis. These deficits were coupled with impairments in the serotonergic pathway in the brain, decreased hippocampal cell proliferation and immature neurons, as well as reduced neural activation. In addition, NodDKO mice had increased gastrointestinal permeability and altered serotonin signalling in the gut following exposure to acute stress. Administration of the selective serotonin reuptake inhibitor, fluoxetine, abrogated behavioural impairments and restored serotonin signalling. We also identified that intestinal epithelial cell-specific deletion of Nod1 (VilCre+ Nod1f/f ), but not Nod2, increased susceptibility to stress-induced anxiety-like behaviour and cognitive impairment following exposure to stress. Together, these data suggest that intestinal epithelial NLR are novel modulators of gut-brain communication and may serve as potential novel therapeutic targets for t

The gut microbiome (GM) contributes to host development, metabolism, and disease. Perturbations in GM composition, elicited through chronic administration of oral antibiotics (Abx) or studied using germ-free environments, alter bone mass, and microarchitecture. However, studies primarily involved chronic Abx exposure to adult mice prior to evaluating the skeletal phenotype. Children are more prone to infection with bacterial pathogens than adults and are thus treated more frequently with broad-spectrum Abx; consequently, Abx treatment disproportionately occurs during periods of greatest skeletal plasticity to anabolic cues. Because early-life exposures may exert long-lasting effects on adult health, we hypothesized that acute Abx administration during a developmentally sensitive period would elicit lasting effects on the skeletal phenotype. To test this hypothesis, neonatal mice were treated with Abx (P7-P23; oral gavage) or vehicle (water); GM composition, gut physiology, and bone structural and material properties were assessed in adulthood (8 weeks). We found sexually dimorphic effects of neonatal Abx administration on GM composition, gut barrier permeability, and the skeleton, indicating a negative role for neonatal Abx on bone mass and quality. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2122-2129, 2019.

Myelination in the peripheral and central nervous systems is critical in regulating motor, sensory, and cognitive functions. As myelination occurs rapidly during early life, neonatal gut dysbiosis during early colonization can potentially alter proper myelination by dysregulating immune responses and neuronal differentiation. Despite common usage of antibiotics (Abx) in children, the impact of neonatal Abx-induced dysbiosis on the development of microbiota, gut, brain (MGB) axis, including myelination and behavior, is unknown. We hypothesized that neonatal Abx-induced dysbiosis dysregulates host-microbe interactions, impairing myelination in the brain, and altering the MGB axis. Neonatal C57BL/6 mice were orally gavaged daily with an Abx cocktail (neomycin, vancomycin, ampicillin) or water (vehicle) from postnatal day 7 (P7) until weaning (P23) to induce gut dysbiosis. Behavior (cognition; anxiety-like behavior), microbiota sequencing, and qPCR (ileum, colon, hippocampus and pre-frontal cortex [PFC]) were performed in adult mice (6-8 weeks). Neonatal Abx administration led to intestinal dysbiosis in adulthood, impaired intestinal physiology, coupled with perturbations of bacterial metabolites and behavioral alterations (cognitive deficits and anxiolytic behavior). Expression of myelin-related genes (Mag, Mog, Mbp, Mobp, Plp) and transcription factors (Sox10, Myrf) important for oligodendrocytes were significantly increased in the PFC region of Abx-treated mice. Increased myelination was confirmed by immunofluorescence imaging and western blot analysis, demonstrating increased expression of MBP, SOX10 and MYRF in neonatally Abx-treated mice compared to sham controls in adulthood. Finally, administration of the short chain fatty acid butyrate following completion of the Abx treatment restored intestinal physiology, behavior, and myelination impairments, suggesting a critical role for the gut microbiota in mediating these effects. Taken together, we identified a l

Restoration is considered an effective strategy to accelerate the recovery of biological communities at local scale. However, the effects of restoration actions in the marine ecosystems are still unpredictable. We performed a global analysis of published literature to identify the factors increasing the probability of restoration success in coastal and marine systems. Our results confirm that the majority of active restoration initiatives are still concentrated in the northern hemisphere and that most of information gathered from restoration efforts derives from a relatively small subset of species. The analysis also indicates that many studies are still experimental in nature, covering small spatial and temporal scales. Despite the limits of assessing restoration effectiveness in absence of a standardized definition of success, the context (degree of human impact, ecosystem type, habitat) of where the restoration activity is undertaken is of greater relevance to a successful outcome than how (method) the restoration is carried out. Contrary to expectations, we found that restoration is not necessarily more successful closer to protected areas (PA) and in areas of moderate human impact. This result can be motivated by the limits in assessing the success of interventions and by the tendency of selecting areas in more obvious need of restoration, where the potential of actively restoring a degraded site is more evident. Restoration sites prioritization considering human uses and conservation status present in the region is of vital importance to obtain the intended outcomes and galvanize further actions.

Global change is striking harder and faster in the Mediterranean Sea than elsewhere, where high levels of human pressure and proneness to climate change interact in mod- ifying the structure and disrupting regulative mechanisms of marine ecosystems. Rocky reefs are particularly exposed to such environmental changes with ongoing trends of degradation being impressive. Due to the variety of habitat types and associated marine biodiversity, rocky reefs are critical for the functioning of marine ecosystems, and their decline could profoundly affect the provision of essential goods and services which human populations in coastal areas rely upon. Here, we provide an up-to-date overview of the status of rocky reefs, trends in human-driven changes undermining their integrity, and current and upcoming management and conservation strategies, attempting a pro- jection on what could be the future of this essential component of Mediterranean marine ecosystems.

Energy storage can make key contributions to balancing future low-carbon energy systems by providing a variety of energy system services, with batteries expected to be widely deployed as costs fall with innovation. This paper assesses whether synergies exist between two of the most significant of these services, fast frequency response and energy arbitrage, if a battery energy storage system (BESS) is used to deliver both. A techno-economic model is developed to simulate 600 possible fast frequency response availability windows. Results show that two distinct synergies exist between the two services. The first synergy accounts for the possibility of charging outside the deadband for delivering fast frequency response. We propose an innovative state-of-charge management strategy to exploit this synergy. The second synergy results from energy arbitrage revenues being highly concentrated around peak times, which can enable a battery system to capture most of the arbitrage revenues without an excessive reduction in revenues from capacity provision with enhanced frequency response. The combination of these two synergies means that a battery system could increase its operating profits by 25% by delivering arbitrage and frequency response alternately. This result is shown to be statistically robust using historical data. A battery system able to discharge for 1.5–2 h at its full power rating will most most likely optimise these synergies.

Energy storage can make key contributions to balancing future low-carbon energy systems by providing a variety of energy system services, with batteries expected to be widely deployed as costs fall with innovation. This paper assesses whether synergies exist between two of the most significant of these services, fast frequency response and energy arbitrage, if a battery energy storage system (BESS) is used to deliver both. A techno-economic model is developed to simulate 600 possible fast frequency response availability windows. Results show that two distinct synergies exist between the two services. The first synergy accounts for the possibility of charging outside the deadband for delivering fast frequency response. We propose an innovative state-of-charge management strategy to exploit this synergy. The second synergy results from energy arbitrage revenues being highly concentrated around peak times, which can enable a battery system to capture most of the arbitrage revenues without an excessive reduction in revenues from capacity provision with enhanced frequency response. The combination of these two synergies means that a battery system could increase its operating profits by 25% by delivering arbitrage and frequency response alternately. This result is shown to be statistically robust using historical data. A battery system able to discharge for 1.5–2 h at its full power rating will most most likely optimise these synergies.

Energy storage can make key contributions to balancing future low-carbon energy systems by providing a variety of energy system services, with batteries expected to be widely deployed as costs fall with innovation. This paper assesses whether synergies exist between two of the most significant of these services, fast frequency response and energy arbitrage, if a battery energy storage system (BESS) is used to deliver both. A techno-economic model is developed to simulate 600 possible fast frequency response availability windows. Results show that two distinct synergies exist between the two services. The first synergy accounts for the possibility of charging outside the deadband for delivering fast frequency response. We propose an innovative state-of-charge management strategy to exploit this synergy. The second synergy results from energy arbitrage revenues being highly concentrated around peak times, which can enable a battery system to capture most of the arbitrage revenues without an excessive reduction in revenues from capacity provision with enhanced frequency response. The combination of these two synergies means that a battery system could increase its operating profits by 25% by delivering arbitrage and frequency response alternately. This result is shown to be statistically robust using historical data. A battery system able to discharge for 1.5–2 h at its full power rating will most most likely optimise these synergies.

© 2020 The Authors Background: The human gut microbiota has emerged as a key factor in the development of obesity. Certain probiotic strains have shown anti-obesity effects. The objective of this study was to investigate whether Bifidobacterium longum APC1472 has anti-obesity effects in high-fat diet (HFD)-induced obese mice and whether B. longum APC1472 supplementation reduces body-mass index (BMI) in healthy overweight/obese individuals as the primary outcome. B. longum APC1472 effects on waist-to-hip ratio (W/H ratio) and on obesity-associated plasma biomarkers were analysed as secondary outcomes. Methods: B. longum APC1472 was administered to HFD-fed C57BL/6 mice in drinking water for 16 weeks. In the human intervention trial, participants received B. longum APC1472 or placebo supplementation for 12 weeks, during which primary and secondary outcomes were measured at the beginning and end of the intervention. Findings: B. longum APC1472 supplementation was associated with decreased bodyweight, fat depots accumulation and increased glucose tolerance in HFD-fed mice. While, in healthy overweight/obese adults, the supplementation of B. longum APC1472 strain did not change primary outcomes of BMI (0.03, 95% CI [-0.4, 0.3]) or W/H ratio (0.003, 95% CI [-0.01, 0.01]), a positive effect on the secondary outcome of fasting blood glucose levels was found (-0.299, 95% CI [-0.44, -0.09]). Interpretation: This study shows a positive translational effect of B. longum APC1472 on fasting blood glucose from a preclinical mouse model of obesity to a human intervention study in otherwise healthy overweight and obese individuals. This highlights the promising potential of B. longum APC1472 to be developed as a valuable supplement in reducing specific markers of obesity. Funding: This r

BACKGROUND: Visceral pain is a complex and heterogeneous disorder, which can range from the mild discomfort of indigestion to the agonizing pain of renal colic. Regulation of visceral pain involves the spinal cord as well as higher order brain structures. Recent findings have linked the microbiota to gastrointestinal disorders characterized by abdominal pain suggesting the ability of microbes to modulate visceral hypersensitivity and nociception to pain. MAIN BODY: In this review we describe the neuroanatomical basis of visceral pain signaling and the existing evidence of its manipulation exerted by the gut microbiota. We included an updated overview of the potential therapeutic effects of dietary intervention, specifically probiotics and prebiotics, in alleviating hypersensitivity to visceral pain stimuli. CONCLUSIONS: The gut microbiota dramatically impacts normal visceral pain sensation and affects the mechanisms mediating visceral nociception. Furthermore, manipulation of the gut microbiota using prebiotics and probiotics plays a potential role in the regulation of visceral pain disorders.

BackgroundVisceral pain is a complex and heterogeneous disorder, which can range from the mild discomfort of indigestion to the agonizing pain of renal colic. Regulation of visceral pain involves the spinal cord as well as higher order brain structures. Recent findings have linked the microbiota to gastrointestinal disorders characterized by abdominal pain suggesting the ability of microbes to modulate visceral hypersensitivity and nociception to pain.Main bodyIn this review we describe the neuroanatomical basis of visceral pain signaling and the existing evidence of its manipulation exerted by the gut microbiota. We included an updated overview of the potential therapeutic effects of dietary intervention, specifically probiotics and prebiotics, in alleviating hypersensitivity to visceral pain stimuli.ConclusionsThe gut microbiota dramatically impacts normal visceral pain sensation and affects the mechanisms mediating visceral nociception. Furthermore, manipulation of the gut microbiota using prebiotics and probiotics plays a potential role in the regulation of visceral pain disorders.

BackgroundVisceral pain is a complex and heterogeneous disorder, which can range from the mild discomfort of indigestion to the agonizing pain of renal colic. Regulation of visceral pain involves the spinal cord as well as higher order brain structures. Recent findings have linked the microbiota to gastrointestinal disorders characterized by abdominal pain suggesting the ability of microbes to modulate visceral hypersensitivity and nociception to pain.Main bodyIn this review we describe the neuroanatomical basis of visceral pain signaling and the existing evidence of its manipulation exerted by the gut microbiota. We included an updated overview of the potential therapeutic effects of dietary intervention, specifically probiotics and prebiotics, in alleviating hypersensitivity to visceral pain stimuli.ConclusionsThe gut microbiota dramatically impacts normal visceral pain sensation and affects the mechanisms mediating visceral nociception. Furthermore, manipulation of the gut microbiota using prebiotics and probiotics plays a potential role in the regulation of visceral pain disorders.

BACKGROUND: Visceral pain is a complex and heterogeneous disorder, which can range from the mild discomfort of indigestion to the agonizing pain of renal colic. Regulation of visceral pain involves the spinal cord as well as higher order brain structures. Recent findings have linked the microbiota to gastrointestinal disorders characterized by abdominal pain suggesting the ability of microbes to modulate visceral hypersensitivity and nociception to pain. MAIN BODY: In this review we describe the neuroanatomical basis of visceral pain signaling and the existing evidence of its manipulation exerted by the gut microbiota. We included an updated overview of the potential therapeutic effects of dietary intervention, specifically probiotics and prebiotics, in alleviating hypersensitivity to visceral pain stimuli. CONCLUSIONS: The gut microbiota dramatically impacts normal visceral pain sensation and affects the mechanisms mediating visceral nociception. Furthermore, manipulation of the gut microbiota using prebiotics and probiotics plays a potential role in the regulation of visceral pain disorders.

Purpose of reviewThe crosstalk between the gut and the brain has revealed a complex communication system responsible for maintaining a proper gastrointestinal homeostasis as well as affect emotional mood and cognitive functions. Recent research has revealed that beneficial manipulation of the microbiota by probiotics and prebiotics represent an emerging and novel strategy for the treatment of a large spectrum of diseases ranging from visceral pain to mood disorders. The review critically evaluates current knowledge of the effects exerted by both probiotics and prebiotics in irritable bowel syndrome (IBS) and mood disorders such as anxiety and depression.Recent findingsRelevant literature was identified through a search of MEDLINE via PubMed using the following words, "probiotics", "prebiotics", "microbiota", and "gut-brain axis" in combination with "stress", "depression", "IBS", and "anxiety". A number of trials have shown efficacy of probiotics and prebiotics in ameliorating both IBS related symptoms and emotional states. However, limitations have been found especially due to the small number of clinical studies, studies design, patient sample size, and placebo effect.SummaryNonetheless, current finding supports the view that beneficial manipulation of the microbiota through both probiotics and prebiotics intake represents a novel attractive strategy to treat gut-brain axis disorders such as IBS and depression.

The rapid response of benthic foraminifera to environmental factors (e.g., organic matter quality and quantity, salinity, pH) and their high fossilisation potential make them promising bio-indicators for the intensity and recurrence of brine formation in Arctic seas. Such approach, however, requires a thorough knowledge of their modern ecology in such extreme settings. To this aim, seven stations along a N–S transect across the Storfjorden (Svalbard archipelago) have been sampled using an interface multicorer. This fjord is an area of intense sea ice formation characterised by the production of Brine-enriched Shelf Waters (BSW) as a result of a recurrent latent-heat polynya. Living (Rose Bengal stained) foraminiferal assemblages were analysed together with geochemical and sedimentological parameters in the top five centimetres of the sediment. Three major biozones were distinguished: (i) the inner fjord dominated by typical glacier proximal calcareous species which opportunistically respond to fresh organic matter inputs; (ii) the deep basins and sill characterised by glacier distal agglutinated faunas. These latter are either dominant because of the mostly refractory nature of organic matter and/or the brine persistence that hampers the growth of calcareous species and/or causes their dissolution. (iii) The outer fjord characterised by typical North Atlantic species due to the intrusion of the North Atlantic water in the Storfjordrenna. The stressful conditions present in the deep basins and sill (i.e. acidic waters and low food quality) result in a high agglutinated/calcareous ratio (A / C). This supports the potential use of the A / C ratio as a proxy for brine persistence and overflow in Storfjorden.

The rapid response of benthic foraminifera to environmental factors (e.g., organic matter quality and quantity, salinity, pH) and their high fossilisation potential make them promising bio-indicators for the intensity and recurrence of brine formation in Arctic seas. Such approach, however, requires a thorough knowledge of their modern ecology in such extreme settings. To this aim, seven stations along a N–S transect across the Storfjorden (Svalbard archipelago) have been sampled using an interface multicorer. This fjord is an area of intense sea ice formation characterised by the production of Brine-enriched Shelf Waters (BSW) as a result of a recurrent latent-heat polynya. Living (Rose Bengal stained) foraminiferal assemblages were analysed together with geochemical and sedimentological parameters in the top five centimetres of the sediment. Three major biozones were distinguished: (i) the inner fjord dominated by typical glacier proximal calcareous species which opportunistically respond to fresh organic matter inputs; (ii) the deep basins and sill characterised by glacier distal agglutinated faunas. These latter are either dominant because of the mostly refractory nature of organic matter and/or the brine persistence that hampers the growth of calcareous species and/or causes their dissolution. (iii) The outer fjord characterised by typical North Atlantic species due to the intrusion of the North Atlantic water in the Storfjordrenna. The stressful conditions present in the deep basins and sill (i.e. acidic waters and low food quality) result in a high agglutinated/calcareous ratio (A / C). This supports the potential use of the A / C ratio as a proxy for brine persistence and overflow in Storfjorden.

The rapid response of benthic foraminifera to environmental factors (e.g., organic matter quality and quantity, salinity, pH) and their high fossilisation potential make them promising bio-indicators for the intensity and recurrence of brine formation in Arctic seas. Such approach, however, requires a thorough knowledge of their modern ecology in such extreme settings. To this aim, seven stations along a N–S transect across the Storfjorden (Svalbard archipelago) have been sampled using an interface multicorer. This fjord is an area of intense sea ice formation characterised by the production of Brine-enriched Shelf Waters (BSW) as a result of a recurrent latent-heat polynya. Living (Rose Bengal stained) foraminiferal assemblages were analysed together with geochemical and sedimentological parameters in the top five centimetres of the sediment. Three major biozones were distinguished: (i) the inner fjord dominated by typical glacier proximal calcareous species which opportunistically respond to fresh organic matter inputs; (ii) the deep basins and sill characterised by glacier distal agglutinated faunas. These latter are either dominant because of the mostly refractory nature of organic matter and/or the brine persistence that hampers the growth of calcareous species and/or causes their dissolution. (iii) The outer fjord characterised by typical North Atlantic species due to the intrusion of the North Atlantic water in the Storfjordrenna. The stressful conditions present in the deep basins and sill (i.e. acidic waters and low food quality) result in a high agglutinated/calcareous ratio (A / C). This supports the potential use of the A / C ratio as a proxy for brine persistence and overflow in Storfjorden.

The rapid response of benthic foraminifera to environmental factors (e.g., organic matter quality and quantity, salinity, pH) and their high fossilisation potential make them promising bio-indicators for the intensity and recurrence of brine formation in Arctic seas. Such approach, however, requires a thorough knowledge of their modern ecology in such extreme settings. To this aim, seven stations along a N–S transect across the Storfjorden (Svalbard archipelago) have been sampled using an interface multicorer. This fjord is an area of intense sea ice formation characterised by the production of Brine-enriched Shelf Waters (BSW) as a result of a recurrent latent-heat polynya. Living (Rose Bengal stained) foraminiferal assemblages were analysed together with geochemical and sedimentological parameters in the top five centimetres of the sediment. Three major biozones were distinguished: (i) the inner fjord dominated by typical glacier proximal calcareous species which opportunistically respond to fresh organic matter inputs; (ii) the deep basins and sill characterised by glacier distal agglutinated faunas. These latter are either dominant because of the mostly refractory nature of organic matter and/or the brine persistence that hampers the growth of calcareous species and/or causes their dissolution. (iii) The outer fjord characterised by typical North Atlantic species due to the intrusion of the North Atlantic water in the Storfjordrenna. The stressful conditions present in the deep basins and sill (i.e. acidic waters and low food quality) result in a high agglutinated/calcareous ratio (A / C). This supports the potential use of the A / C ratio as a proxy for brine persistence and overflow in Storfjorden.

The impacts of bottom trawling on the structure of benthic communities can be relatively nonselective, hitting biodiversity as a whole. This holds true also in the deep sea, where the impacts of trawling can be more severe and long-lasting than in shallow-waters, due to the reduced capacity for recovery and greater vulnerability of deep-sea organisms. For years, our knowledge of the impact of trawling on deep-water ecosystems has remained limited and has focused mainly on fish stocks and hard bottom systems. More recently, a number of studies have addressed the impacts of bottom trawling in the deep-sea sedimentary environments, and very few of them have focused on the impacts on meiofauna, though it is a key faunal component of deep-sea ecosystems. We investigated the impact of bottom trawling on the quantity, biochemical composition and nutritional value of sedimentary organic matter and meiofauna along the Sicilian Margin (Gulf of Castellammare, southwestern Mediterranean) at ca. 550 m depth, during the summer of 2016. Amount, biochemical composition and freshness of sedimentary OM, as well as the abundance and community composition of meiofauna were determined in sediment cores taken at both trawled and untrawled grounds. The continuous erosive processes in the trawled site have led, generally, to the depletion of OM contents (20-60% lower than those in the untrawled site), as well as to statistically significant differences from the untrawled site in its biochemical composition. Nevertheless, the upper 2 cm of the trawled site consisted of recently accumulated sediments, enriched in phytopigments, and bulk OM contents similar to those in the untrawled one, interpreted as a very recent input of fresh OM from the upper water column. The abundance of meiofauna in trawled grounds was significantly higher than that in untrawled ones, whereas no differences were observed between trawled and untrawled grounds deeper in the sediment. Differences in the meiofaunal commu

Bottom trawling in the deep sea is one of the main drivers of sediment resuspension, eroding the seafloor and altering the content and composition of sedimentary organic matter (OM). The physical and biogeochemical impacts of bottom trawling were studied on the continental slope of the Gulf of Castellammare, Sicily (southwestern Mediterranean), through the analysis of two triplicate sediment cores collected at trawled and untrawled sites (∼550 m water depth) during the summer of 2016. Geochemical and sedimentological parameters (excess 210Pb, excess 234Th, 137Cs, dry bulk density, and grain size), elemental (organic carbon and nitrogen) and biochemical composition of sedimentary OM (proteins, carbohydrates, lipids), as well as its freshness (phytopigments) and degradation rates were determined in both coring locations. The untrawled site had a sedimentation rate of 0.15 cm yr−1 and presented a 6 cm thick surface mixed layer that contained siltier sediment with low excess 210Pb concentrations, possibly resulting from the resuspension, posterior advection, and eventual deposition of coarser and older sediment from adjacent trawling grounds. In contrast, the trawled site was eroded and presented compacted century-old sediment highly depleted in OM components, which were between 20 % and 60 % lower than those in the untrawled site. However, the upper 2 cm of the trawled site consisted of recently accumulated sediments enriched in excess 234Th, excess 210Pb, and phytopigments, while OM contents were similar to those from the untrawled core. This fresh sediment supported protein turnover rates of 0.025 d−1, which doubled those quantified in surface sediments of the untrawled site. The enhancement of remineralization rates in surface sediment of the trawled site was associated with the arrival of fresh particles on a chronically trawled deep-sea region that is generally deprived of OM. We conclude that the detrimental effects of bottom trawling can be temporarily and parti

Bottom trawling in the deep sea is one of the main drivers of sediment resuspension, eroding the seafloor and altering the content and composition of sedimentary organic matter (OM). The physical and biogeochemical impacts of bottom trawling were studied on the continental slope of the Gulf of Castellammare, Sicily (southwestern Mediterranean), through the analysis of two triplicate sediment cores collected at trawled and untrawled sites (∼550 m water depth) during the summer of 2016. Geochemical and sedimentological parameters (excess 210Pb, excess 234Th, 137Cs, dry bulk density, and grain size), elemental (organic carbon and nitrogen) and biochemical composition of sedimentary OM (proteins, carbohydrates, lipids), as well as its freshness (phytopigments) and degradation rates were determined in both coring locations. The untrawled site had a sedimentation rate of 0.15 cm yr−1 and presented a 6 cm thick surface mixed layer that contained siltier sediment with low excess 210Pb concentrations, possibly resulting from the resuspension, posterior advection, and eventual deposition of coarser and older sediment from adjacent trawling grounds. In contrast, the trawled site was eroded and presented compacted century-old sediment highly depleted in OM components, which were between 20 % and 60 % lower than those in the untrawled site. However, the upper 2 cm of the trawled site consisted of recently accumulated sediments enriched in excess 234Th, excess 210Pb, and phytopigments, while OM contents were similar to those from the untrawled core. This fresh sediment supported protein turnover rates of 0.025 d−1, which doubled those quantified in surface sediments of the untrawled site. The enhancement of remineralization rates in surface sediment of the trawled site was associated with the arrival of fresh particles on a chronically trawled deep-sea region that is generally deprived of OM. We conclude that the detrimental effects of bottom trawling can be temporarily and parti

Bottom trawling in the deep sea is one of the main drivers of sediment resuspension, eroding the seafloor and altering the content and composition of sedimentary organic matter (OM). The physical and biogeochemical impacts of bottom trawling were studied on the continental slope of the Gulf of Castellammare, Sicily (southwestern Mediterranean), through the analysis of two triplicate sediment cores collected at trawled and untrawled sites (∼550 m water depth) during the summer of 2016. Geochemical and sedimentological parameters (excess 210Pb, excess 234Th, 137Cs, dry bulk density, and grain size), elemental (organic carbon and nitrogen) and biochemical composition of sedimentary OM (proteins, carbohydrates, lipids), as well as its freshness (phytopigments) and degradation rates were determined in both coring locations. The untrawled site had a sedimentation rate of 0.15 cm yr−1 and presented a 6 cm thick surface mixed layer that contained siltier sediment with low excess 210Pb concentrations, possibly resulting from the resuspension, posterior advection, and eventual deposition of coarser and older sediment from adjacent trawling grounds. In contrast, the trawled site was eroded and presented compacted century-old sediment highly depleted in OM components, which were between 20 % and 60 % lower than those in the untrawled site. However, the upper 2 cm of the trawled site consisted of recently accumulated sediments enriched in excess 234Th, excess 210Pb, and phytopigments, while OM contents were similar to those from the untrawled core. This fresh sediment supported protein turnover rates of 0.025 d−1, which doubled those quantified in surface sediments of the untrawled site. The enhancement of remineralization rates in surface sediment of the trawled site was associated with the arrival of fresh particles on a chronically trawled deep-sea region that is generally deprived of OM. We conclude that the detrimental effects of bottom trawling can be temporarily and parti

Bottom trawling in the deep sea is one of the main drivers of sediment resuspension, eroding the seafloor and altering the content and composition of sedimentary organic matter (OM). The physical and biogeochemical impacts of bottom trawling were studied on the continental slope of the Gulf of Castellammare, Sicily (southwestern Mediterranean), through the analysis of two triplicate sediment cores collected at trawled and untrawled sites (∼550 m water depth) during the summer of 2016. Geochemical and sedimentological parameters (excess 210Pb, excess 234Th, 137Cs, dry bulk density, and grain size), elemental (organic carbon and nitrogen) and biochemical composition of sedimentary OM (proteins, carbohydrates, lipids), as well as its freshness (phytopigments) and degradation rates were determined in both coring locations. The untrawled site had a sedimentation rate of 0.15 cm yr−1 and presented a 6 cm thick surface mixed layer that contained siltier sediment with low excess 210Pb concentrations, possibly resulting from the resuspension, posterior advection, and eventual deposition of coarser and older sediment from adjacent trawling grounds. In contrast, the trawled site was eroded and presented compacted century-old sediment highly depleted in OM components, which were between 20 % and 60 % lower than those in the untrawled site. However, the upper 2 cm of the trawled site consisted of recently accumulated sediments enriched in excess 234Th, excess 210Pb, and phytopigments, while OM contents were similar to those from the untrawled core. This fresh sediment supported protein turnover rates of 0.025 d−1, which doubled those quantified in surface sediments of the untrawled site. The enhancement of remineralization rates in surface sediment of the trawled site was associated with the arrival of fresh particles on a chronically trawled deep-sea region that is generally deprived of OM. We conclude that the detrimental effects of bottom trawling can be temporarily and parti

Bottom trawling in the deep sea is one of the main drivers of sediment resuspension, eroding the seafloor and altering the content and composition of sedimentary organic matter (OM). The physical and biogeochemical impacts of bottom trawling were studied on the continental slope of the Gulf of Castellammare, Sicily (southwestern Mediterranean), through the analysis of two triplicate sediment cores collected at trawled and untrawled sites (∼550 m water depth) during the summer of 2016. Geochemical and sedimentological parameters (excess 210Pb, excess 234Th, 137Cs, dry bulk density, and grain size), elemental (organic carbon and nitrogen) and biochemical composition of sedimentary OM (proteins, carbohydrates, lipids), as well as its freshness (phytopigments) and degradation rates were determined in both coring locations. The untrawled site had a sedimentation rate of 0.15 cm yr−1 and presented a 6 cm thick surface mixed layer that contained siltier sediment with low excess 210Pb concentrations, possibly resulting from the resuspension, posterior advection, and eventual deposition of coarser and older sediment from adjacent trawling grounds. In contrast, the trawled site was eroded and presented compacted century-old sediment highly depleted in OM components, which were between 20 % and 60 % lower than those in the untrawled site. However, the upper 2 cm of the trawled site consisted of recently accumulated sediments enriched in excess 234Th, excess 210Pb, and phytopigments, while OM contents were similar to those from the untrawled core. This fresh sediment supported protein turnover rates of 0.025 d−1, which doubled those quantified in surface sediments of the untrawled site. The enhancement of remineralization rates in surface sediment of the trawled site was associated with the arrival of fresh particles on a chronically trawled deep-sea region that is generally deprived of OM. We conclude that the detrimental effects of bottom trawling can be temporarily and parti

El objetivo de este estudio es proponer un método adaptable, multidisciplinario y todo incluido, que considere la intervención en el sistema de infraestructura y los nodos como una prioridad estratégica, con el fin de garantizar un nivel de planificación que permita la concatenación de intervenciones posteriores.El desarrollo de un método finaliza con la implementación de las acciones necesarias para completar un plan estratégico dirigido a una transformación radical de la ciudad. El estudio de caso presentó acuerdos con la estación de Termini y la ciudad de Roma, con el objetivo a largo plazo de revertir la tendencia en los patrones de movilidad y mejorar el área dentro de los Muros de Aurelia (patrimonio de la UNESCO). El estado actual de los sistemas y nodos de infraestructura ofrece posibilidades, a veces respaldadas por un debate arraigado en el tiempo, capaces de abordar los intereses de varios actores. Por lo tanto, al establecer la intervención en la infraestructura como el primer paso, necesario para recalibrar el equilibrio entre los sistemas urbanos, es posible obtener una vista previa de los efectos directos en los nodos y en la ciudad que permiten nuevas transformaciones. Entre estos, la recuperación del suelo urbano es un paso fundamental del método, que se puede lograr enterrando parte de la infraestructura o las estaciones. La viabilidad de proyectos de esta escala a menudo está vinculada a la liberalización del sistema ferroviario, que ha dado la propiedad de las áreas a empresas públicas regidas por el derecho privado, convirtiéndolas en promotoras y garantes de las transformaciones, a través de acuerdos con las autoridades públicas.Sobre la base de la transformación del sistema de infraestructura, es posible llevar a cabo intervenciones en movilidad, en el sistema ambiental y en la recalificación urbana, capaces de establecer las principales líneas de desarrollo de la ciudad. Estas intervenciones pueden extenderse en el tiempo, para que la transfo, L’objectiu d’aquest estudi és un promotor d’un mètode adaptable, multidisciplinari i tot inclòs, que considera la intervenció en el sistema de infraestructura i els nodes com una prioritat estratègica, amb l’objectiu de garantir un nivell de planificació que permeti la concatenació d’intervencions posteriors.El desenvolupament d’un mètode finalitzarà amb la implementació de les accions necessàries per completar un pla estratègic dirigit a una transformació radical de la ciutat. L’estudi de cas presentava acords amb l’estació de Termini i la ciutat de Roma, amb l’objectiu d’un llarg pla de revertir la tendència en els patrons de la mobilitat i millorar l’àrea dins dels Murs d’Aurelia (patrimoni de la UNESCO). L’estat actual dels sistemes i nodes de infraestructura ofereix possibilitats, algunes vegades respostes per un debat encarregat en el temps, capacitats d’abordar els interessos de diversos actors. Per tant, s’establirà la intervenció en la infraestructura com el primer pas, necessari per recalibrar l’equilibri entre els sistemes urbans, és possible obtenir una vista prèvia dels efectes directes als nodes i a la ciutat que permeten noves transformacions. Entre aquests, la recuperació del sòl urbà és un pas fonamental del mètode, que es pot aconseguir entrar en una part de la infraestructura o de les estacions. La viabilitat de projectes d’aquesta escala i menús està vinculada a la liberalització del sistema ferroviari, que tenia la propietat de les àrees d’empreses públiques regides pel dret privat, convertint-les en promocions i garanties de les transformacions, a través d’acords amb les autoritats públiques.Sobre la base de la transformació del sistema de infraestructura, és possible portar a terme intervencions en moviment, en el sistema ambiental i en la recalificació urbana, capaços d’establir les principals línies de desenvolupament de la ciutat. Són intervencions que es poden estendre al llarg del temps, per a la transformació d’un mar urbà sostenible i m, The aim of this study is to propose an adaptable, multidisciplinary and all-inclusive method, which considers the intervention on the infrastructure system and nodes as a strategic priority, in order to ensure a level of planning that allows the concatenation of subsequent interventions.The development of a method is finalized to the implementation of the necessary actions to complete a strategic plan aimed at a radical transformation of the city. The case-study presented deals with Termini station and the city of Rome, with the long-term objective of reversing the trend in mobility patterns and enhancing the area within the Aurelian Walls (UNESCO heritage). The current state of infrastructure systems and nodes offers possibilities, sometimes supported by a debate rooted in time, able to address the interests of various actors. Therefore, by establishing the intervention on the infrastructure as the first step, necessary to recalibrate the balance between the urban systems, it is possible to preview direct effects on the nodes and on the city that allow to further transformations. Among these, the recovery of urban land is a fundamental step of the method, achievable through the burying of part of the infrastructure or stations. The feasibility of projects of this scale is often linked to the liberalisation of the railway system, which has given ownership of the areas to public companies governed by private law, making them promoters and guarantors of the transformations, through agreements with public authorities.On the base of the transformation of the infrastructural system, it is possible to carry out interventions on mobility, on the environmental system and of urban requalification, able to establish the main lines of development of the city. These interventions can be extended in time, in order to make urban transformation sustainable and less radical, and must work as catalysts to achieve the strategic objectives preponed. To provide a guideline for future p, Peer Reviewed

Claudio Pusceddu,1 Panagiotis Paliogiannis,2 Giuseppe Nigri,3 Alessandro Fancellu4 1Division of Interventional Radiology, Department of Oncologic Radiology, Businco Hospital, Cagliari, Italy; 2Unit of Experimental Pathology and Oncology, Department of Medical Surgical and Experimental Sciences, University of Sassari, Sassari, Italy; 3Department of Medical and Surgical Sciences and Translational Medicine, Sapienza University of Rome, St. Andrea University Hospital, Rome, Italy; 4Unit of General Surgery 2 - Clinica Chirurgica, Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, ItalyCorrespondence: Alessandro FancelluUniversity of Sassari, Department of Medical, Surgical and Experimental Sciences, Unit of General Surgery 2 - Clinica Chirurgica, V.le San Pietro 43, Sassari 07100, ItalyTel +39 079 228432Fax +39 079 228394Email afancel@uniss.itAbstract: Cryoablation has been successfully used to treat various type of solid tumors, including breast carcinomas. This ablation method has the advantage of being a minimally invasive procedure useful in various clinical situations, including early breast cancer and metastatic breast cancer, when co-morbidities preclude the use of surgical treatment. However, due to the small sample size of the available studies, reliable and definitive conclusions on the usefulness of cryoablation in patients with breast cancer could not be drawn. In fact, many aspects necessitate to be elucidated, regarding technical issues, indications, efficacy, imaging follow-up, and possible advantages over other percutaneous ablative methods. This review article has the aim to clarify the current evidence supporting cryoablation of breast cancer, and discuss the future perspectives, including those arising from the new studies on immunological effects related to cryoablation.Keywords: cryoablation, breast cancer, ablation, treatment, interventional radiology

Gut-brain axis signalling is critical for maintaining health and homeostasis. Stressful life events can impact gut-brain signalling, leading to altered mood, cognition and intestinal dysfunction. In the present study, we identified nucleotide binding oligomerization domain (Nod)-like receptors (NLR), Nod1 and Nod2, as novel regulators for gut-brain signalling. NLR are innate immune pattern recognition receptors expressed in the gut and brain, and are important in the regulation of gastrointestinal physiology. We found that mice deficient in both Nod1 and Nod2 (NodDKO) demonstrate signs of stress-induced anxiety, cognitive impairment and depression in the context of a hyperactive hypothalamic-pituitary-adrenal axis. These deficits were coupled with impairments in the serotonergic pathway in the brain, decreased hippocampal cell proliferation and immature neurons, as well as reduced neural activation. In addition, NodDKO mice had increased gastrointestinal permeability and altered serotonin signalling in the gut following exposure to acute stress. Administration of the selective serotonin reuptake inhibitor, fluoxetine, abrogated behavioural impairments and restored serotonin signalling. We also identified that intestinal epithelial cell-specific deletion of Nod1 (VilCre(+)Nod1(f/f)), but not Nod2, increased susceptibility to stress-induced anxiety-like behaviour and cognitive impairment following exposure to stress. Together, these data suggest that intestinal epithelial NLR are novel modulators of gut-brain communication and may serve as potential novel therapeutic targets for the treatment of gut-brain disorders.

Although propagule pressure is recognized as an important determinant of invasion dynamics, the role of propagule quality (i.e. the physical condition of a propagule) has received little attention. In particular, how the performance of vegetative propagules differing in quality varies across heterogeneous landscapes is yet to be explored. Caulerpa cylindracea is a clonal, invasive seaweed, widely distributed in the Mediterranean. By means of a laboratory experiment, we investigated how variation in the quality of seaweed fragments (intact vs. frond-removal vs. rhizoid-removal) influenced their survival on control versus sediments enriched with detritus from the native seagrass, Posidonia oceanica. The survival of seaweed fragments was low on non-enriched sediments, irrespective of their characteristics. On enriched sediments, survival was high in control and rhizoid-removal fragments, but low in frond-removal fragments. Our study shows that both fragment quality and sediment characteristics influence the survival of C. cylindracea propagules and, hence, long-term spreading dynamics of this seaweed. More generally, it brings novel evidence showing that the effects of propagule quality on invasion success are context-dependent.

Whilst the successful establishment and spread of invasive species can be determined by above-ground processes, results are often equivocal. Emergent research, mostly from terrestrial ecosystems, demonstrates that below-ground processes (nutrient cycling, chemical properties) under microbial control can mediate interactions between native and invasive plants. Because microbes can control similar sediment properties in marine ecosystem that influence plant fitness, we argue that below-ground properties should also exert strong control interactions between native and invasive marine macrophytes. We coupled surveys of microbial communities and chemistry of sediments collected from an invasive alga (Caulerpa cylindracea), a native competitor (the seagrass Posidonia oceanica) and unvegetated sediments with a large field experiment, in which we manipulated the presence/absence of the canopies of both species to determine the effects of above- and below-ground processes on the success of C. cylindracea. Posidonia oceanica and C. cylindracea sediments have microbial communities and predicted metabolic process that reflect aerobic and anaerobic conditions, respectively. Moreover, the nutritional quantity of organic matter was higher, but quality lower in C. cylindracea sediments compared to the two native habitats. The growth of C. cylindracea fragments was equally low in the presence or absence of a P. oceanica canopy, whereas the growth of C. cylindracea was higher in the canopy removed vs. present treatment, possibly because, in the absence of a C. cylindracea canopy, fragments are released from intraspecific competition for resources. Synthesis. Sediment/soil processes are increasingly recognized as important drivers of the success and hence impacts of invasive plants. We extended this theory to marine ecosystems and suggest biotic resistance to invasion may not always be attributable to intact canopies, but may also result from indirect effects of native macrophytes on

A review of 573 studies on active restoration actions in the marine environment, published in the last 25 years, was carried out at global scale. We assessed how, where, at which spatial and temporal scales and under which socio-ecological settings restoration studies have been carried out, from very shallow to deep sea habitats. Results show that restoration efforts across habitats are increasing, especially in seagrasses and coral reefs, but never approached at ecosystem level. Targets, methods, response variables and standards are still very heterogeneous. Of the factors considered in the review, habitat, human impact intensity, realm and methods of restoration were found to be good determinant of restoration success. Short project duration (one-two years), small restoration areas (< 1 ha), lack of controls and knowledge of baselines are still a limit for deriving generalities. Finally, restorations rarely consider future challenges linked to global change this impairing long-term success stories. Restoration science needs more robust approaches leading to the development of best practices (e.g. protocols, monitoring of the effects, reasons for failure) to be applied at spatial and temporal scales so as to answer to present and future disturbance regimes.

A review of 573 studies on active restoration actions in the marine environment, published in the last 25 years, was carried out at global scale. We assessed how, where, at which spatial and temporal scales and under which socio-ecological settings restoration studies have been carried out, from very shallow to deep sea habitats. Results show that restoration efforts across habitats are increasing, especially in seagrasses and coral reefs, but never approached at ecosystem level. Targets, methods, response variables and standards are still very heterogeneous. Of the factors considered in the review, habitat, human impact intensity, realm and methods of restoration were found to be good determinant of restoration success. Short project duration (one-two years), small restoration areas (< 1 ha), lack of controls and knowledge of baselines are still a limit for deriving generalities. Finally, restorations rarely consider future challenges linked to global change this impairing long-term success stories. Restoration science needs more robust approaches leading to the development of best practices (e.g. protocols, monitoring of the effects, reasons for failure) to be applied at spatial and temporal scales so as to answer to present and future disturbance regimes.