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Piton de la Fournaise, situated on La Réunion island (France), is one of the most active hot spot basaltic shield volcanoes worldwide, experiencing at least two eruptions per year since the establishment of the volcanological observatory in 1979. Eruptions are typically fissure-fed and form extensive lava flow fields. About 95 % of some ∼ 250 historical events (since the first confidently dated eruption in 1708) have occurred inside an uninhabited horseshoe-shaped caldera (hereafter referred to as the Enclos), which is open to the ocean on its eastern side. Rarely (12 times since the 18th century), fissures have opened outside of the Enclos, where housing units, population centers, and infrastructure are at risk. In such a situation, lava flow hazard maps are a useful way of visualizing lava flow inundation probabilities over large areas. Here, we present the up-to-date lava flow hazard map for Piton de la Fournaise based on (i) vent distribution, (ii) lava flow recurrence times, (iii) statistics of lava flow lengths, and (iv) simulations of lava flow paths using the DOWNFLOW stochastic numerical model. The map of the entire volcano highlights the spatial distribution probability of future lava flow invasion for the medium to long term (years to decades). It shows that the most probable location for future lava flow is within the Enclos (where there are areas with up to 12 % probability), a location visited by more than 100 000 visitors every year. Outside of the Enclos, probabilities reach 0.5 % along the active rift zones. Although lava flow hazard occurrence in inhabited areas is deemed to be very low (< 0.1 %), it may be underestimated as our study is only based on post-18th century records and neglects older events. We also provide a series of lava flow hazard maps inside the Enclos, computed on a multi-temporal (i.e., regularly updated) topography. Although hazard distribution remains broadly the same over time, some changes are noticed throughout the analyzed periods due to improved digital elevation model (DEM) resolution, the high frequency of eruptions that constantly modifies the topography, and the lava flow dimensional characteristics and paths. The lava flow hazard map for Piton de la Fournaise presented here is reliable and trustworthy for long-term hazard assessment and land use planning and management. Specific hazard maps for short-term hazard assessment (e.g., for responding to volcanic crises) or considering the cycles of activity at the volcano and different event scenarios (i.e., events fed by different combinations of temporally evolving superficial and deep sources) are required for further assessment of affected areas in the future – especially by atypical but potentially extremely hazardous large-volume eruptions. At such an active site, our method supports the need for regular updates of DEMs and associated lava flow hazard maps if we are to be effective in keeping up to date with mitigation of the associated risks.

Volcanic plumes are common and far-reaching manifestations of volcanic activity during and between eruptions. Observations of the rate of emission and composition of volcanic plumes are essential to recognize and, in some cases, predict the state of volcanic activity. Measurements of the size and location of the plumes are important to assess the impact of the emission from sporadic or localized events to persistent or widespread processes of climatic and environmental importance. These observations provide information on volatile budgets on Earth, chemical evolution of magmas, and atmospheric circulation and dynamics. Space-based observations during the last decades have given us a global view of Earth's volcanic emission, particularly of sulfur dioxide (SO2). Although none of the satellite missions were intended to be used for measurement of volcanic gas emission, specially adapted algorithms have produced time-averaged global emission budgets. These have confirmed that tropospheric plumes, produced from persistent degassing of weak sources, dominate the total emission of volcanic SO2. Although space-based observations have provided this global insight into some aspects of Earth's volcanism, it still has important limitations. The magnitude and short-term variability of lower-atmosphere emissions, historically less accessible from space, remain largely uncertain. Operational monitoring of volcanic plumes, at scales relevant for adequate surveillance, has been facilitated through the use of ground-based scanning differential optical absorption spectrometer (ScanDOAS) instruments since the beginning of this century, largely due to the coordinated effort of the Network for Observation of Volcanic and Atmospheric Change (NOVAC). In this study, we present a compilation of results of homogenized post-analysis of measurements of SO2 flux and plume parameters obtained during the period March 2005 to January 2017 of 32 volcanoes in NOVAC. This inventory opens a window into the short-term emission patterns of a diverse set of volcanoes in terms of magma composition, geographical location, magnitude of emission, and style of eruptive activity. We find that passive volcanic degassing is by no means a stationary process in time and that large sub-daily variability is observed in the flux of volcanic gases, which has implications for emission budgets produced using short-term, sporadic observations. The use of a standard evaluation method allows for intercomparison between different volcanoes and between ground- and space-based measurements of the same volcanoes. The emission of several weakly degassing volcanoes, undetected by satellites, is presented for the first time. We also compare our results with those reported in the literature, providing ranges of variability in emission not accessible in the past. The open-access data repository introduced in this article will enable further exploitation of this unique dataset, with a focus on volcanological research, risk assessment, satellite-sensor validation, and improved quantification of the prevalent tropospheric component of global volcanic emission. Datasets for each volcano are made available at https://novac.chalmers.se (last access: 1 October 2020) under the CC-BY 4 license or through the DOI (digital object identifier) links provided in Table 1.

The 2014 eruption at Piton de la Fournaise (PdF), La Réunion, which occurred after 41 months of quiescence, began with surprisingly little precursory activity and was one of the smallest so far observed at PdF in terms of duration (less than 2 days) and volume (less than 0.4 × 106 m3). The pyroclastic material was composed of golden basaltic pumice along with fluidal, spiny iridescent and spiny opaque basaltic scoria. Density analyses performed on 200 lapilli reveal that while the spiny opaque clasts are the densest (1600 kg m−3) and most crystalline (55 vol. %), the golden pumices are the least dense (400 kg m−3) and crystalline (8 vol. %). The connectivity data indicate that the fluidal and golden (Hawaiian-like) clasts have more isolated vesicles (up to 40 vol. %) than the spiny (Strombolian-like) clasts (0–5 vol. %). These textural variations are linked to primary pre-eruptive magma storage conditions. The golden and fluidal fragments track the hotter portion of the melt, in contrast to the spiny fragments and lava that mirror the cooler portion of the shallow reservoir. Exponential decay of the magma ascent and output rates through time revealed depressurization of the source during which a stratified storage system was progressively tapped. Increasing syn-eruptive degassing and melt–gas decoupling led to a decrease in the explosive intensity from early fountaining to Strombolian activity. The geochemical results confirm the absence of new input of hot magma into the 2014 reservoir and confirm the emission of a single shallow, differentiated magma source, possibly related to residual magma from the November 2009 eruption. Fast volatile exsolution and crystal–melt separation (second boiling) were triggered by deep pre-eruptive magma transfer and stress field change. Our study highlights the possibility that shallow magma pockets can be quickly reactivated by deep processes without mass or energy (heat) transfer and produce hazardous eruptions with only short-term elusive precursors.

Abstract Many active European volcanoes and volcano observatories are island-based and located far from their administrative “mainland”. Consequently, Governments have developed multisite approaches, in which monitoring is performed by a network of individuals distributed across several national research centers. At a transnational level, multinational networks are also progressively emerging. Piton de la Fournaise (La Réunion Island, France) is one such example. Piton de la Fournaise is one of the most active volcanoes of the World, and is located at the greatest distance from its “mainland” than any other vulnerable “overseas” site, the observatory being 9365 km from its governing body in Paris. Effusive risk is high, so that a well-coordinated and rapid response involving near-real time delivery of trusted, validated and operational product for hazard assessment is critical. Here we review how near-real time assessments of lava flow propagation were developed using rapid provision, and update, of key source terms through a dynamic and open integration of near-real time remote sensing, modeling and measurement capabilities on both the national and international level. The multi-national system evolved during the five effusive crises of 2014–2015, and is now mature for Piton de la Fournaise. This review allows us to identify strong and weak points in an extended observatory system, and demonstrates that enhanced multi-national integration can have fundamental implications in scientific hazard assessment and response during an on-going effusive crisis.

The STRAP (Synergie Transdisciplinaire pour Répondre aux Aléas liés aux Panaches volcaniques) campaign was conducted over the entire year of 2015 to investigate the volcanic plumes of Piton de La Fournaise (La Réunion, France). For the first time, measurements at the local (near the vent) and at the regional scales were conducted around the island. The STRAP 2015 campaign has become possible thanks to strong cross-disciplinary collaboration between volcanologists and meteorologists. The main observations during four eruptive periods (85 days) are summarised. They include the estimates of SO2, CO2 and H2O emissions, the altitude of the plume at the vent and over different areas of La Réunion Island, the evolution of the SO2 concentration, the aerosol size distribution and the aerosol extinction profile. A climatology of the volcanic plume dispersion is also reported. Simulations and measurements show that the plumes formed by weak eruptions have a stronger interaction with the surface of the island. Strong SO2 mixing ratio and particle concentrations above 1000 ppb and 50 000 cm−3 respectively are frequently measured over a distance of 20 km from Piton de la Fournaise. The measured aerosol size distribution shows the predominance of small particles in the volcanic plume. Several cases of strong nucleation of sulfuric acid have been observed within the plume and at the distal site of the Maïdo observatory. The STRAP 2015 campaign provides a unique set of multi-disciplinary data that can now be used by modellers to improve the numerical parameterisations of the physical and chemical evolution of the volcanic plumes.

Vincenzo Vestuto,1,&ast; Marisa Conte,1,&ast; Mariapia Vietri,1,&ast; Francesca Mensitieri,2 Valentina Santoro,1,3 Anna Di Muro,1 Mariaevelina Alfieri,4 Maria Moros,5,6 Maria Rosaria Miranda,1,3 Chiara Amante,1 Matteo Delli Carri,1 Pietro Campiglia,1 Fabrizio Dal Piaz,2,7 Pasquale Del Gaudio,1 Nunziatina De Tommasi,1,3 Antonietta Leone,1 Ornella Moltedo,1 Giacomo Pepe,1,3 Elisa Cappetta,1 Alfredo Ambrosone1 1Department of Pharmacy, University of Salerno, Fisciano, 84084, Italy; 2Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, Baronissi, 84081, Italy; 3National Biodiversity Future Center (NBFC), Palermo, 90133, Italy; 4Clinical Pathology, Santobono-Pausilipon Children’s Hospital, AORN, Naples, 80122, Italy; 5Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC-Universidad de Zaragoza, Zaragoza, Spain; 6Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain; 7Operative Unit of Clinical Pharmacology, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, Salerno, 84131, Italy&ast;These authors contributed equally to this workCorrespondence: Alfredo Ambrosone; Elisa Cappetta, Department of Pharmacy, University of Salerno, Fisciano, 84084, Italy, Email aambrosone@unisa.it; ecappetta@unisa.itPurpose: Extracellular vesicles (EVs) are promising tools for nanomedicine and nanobiotechnology. The purification of mammalian-derived EVs involves intensive processes, and their therapeutic application raises multiple safety and regulatory issues. Plants have the potential to serve as nonconventional sources of therapeutically relevant EVs. In this context, we recently identified hairy roots (HRs) of medicinal plants as a novel biotechnological platform to produce EVs for human health.Methods: Herein, we report the purification, omics profiling, and bioactivity of EVs isolated from HRs of the medicinal plants S. sclarea and S. dominica. EVs were isolated from conditioned media of HR cultures using differential ultracentrifugation (dUC) and size exclusion chromatography (SEC). The isolated EVs were characterized by nanoparticle tracking analysis (NTA) and electron microscopy. The proteomic and metabolomic profiles of the EVs were determined using mass spectrometry. Uptake studies and bioactivity assays, including confocal microscopy, MTT, flow cytometry, ROS quantification, and untargeted metabolomics analyses, were conducted in SH-SY5Y cells treated with the neurotoxin 6-hydroxydopamine (6-OHDA) to evaluate the therapeutic potential of EVs in an in vitro model of Parkinson’s disease.Results: S. sclarea HRs released nanosized round-shaped EVs with a distinctive molecular signature. HR EVs from S. sclarea and S. dominica revealed conserved cargo of secondary metabolites, predominantly triterpenoids, which are known for their antioxidant properties. We showed that HR EVs are safe, enter the cells, and strongly inhibit apoptosis in a cellular model of Parkinson’s disease. Cellular metabolomics revealed that EVs preserved metabolic homeostasis and mitigated cellular oxidative stress when co-administered with 6-OHDA. Mechanistically, HR EVs inhibited 6-OHDA autoxidation and substantially reduced the accumulation of its oxidative products, which are responsible for 6-OHDA-induced toxicity.Conclusion: Collectively, our findings provide compelling evidence that EVs isolated from the hairy roots of Salvia species are promising, non-mammalian alternative for the design of novel therapies targeting neurological disorders. Keywords: non-mammalian EV source, Salvia extracellular vesicles, hairy roots, nanomedicine, neuroprotection, Parkinson’s disease

In mesoscale models (resolution ~ 1 km) used for regional dispersion of pollution plumes the volcanic heat sources and emissions of gases and aerosols, as well as the induced atmospheric convective motions, are all sub-grid-scale processes (mostly true for weak effusive eruptions) which need to be parameterised. We propose a modified formulation of the EDMF scheme (eddy diffusivity/mass flux) proposed by Pergaud et al. (2009) which is based on a single sub-grid updraft model. It is used to represent volcano induced updrafts tested for a case study of the January 2010 summit eruption of Piton de la Fournaise (PdF) volcano. The validation of this modified formulation using a reference large eddy simulation (LES) focuses on the ability of the model to transport tracer concentrations up to 1–2 km above the ground in the lower troposphere as is the case of majority of PdF eruptions. The modelled volcanic plume agrees reasonably with the profiles of SO2 (sulfur dioxide) tracer concentrations and specific humidity found from the reference LES. Sensitivity tests performed for the modified formulation of the EDMF scheme emphasise the sensitivity of the parameterisation to ambient fresh air entrainment at the plume base.

Posterior lateral meniscal root (PLMR) tears are commonly observed in conjunction with anterior cruciate ligament (ACL) injuries. The presence of PLMR tears exacerbates knee instability, increasing stress on ACL grafts and accelerating joint degeneration if left untreated. Anatomical repair of PLMR tears is therefore crucial for restoring native knee kinematics and reducing tibiofemoral contact pressures, thereby safeguarding the ACL graft. However, the standard use of a single medial tunnel approach for concomitant PLMR and revision ACL reconstruction may require reconsideration to prevent the potential risks of tunnel overlapping, which could undermine graft anatomical integrity. This article, to prevent the risk of tunnel overlapping, introduces a surgical approach that employs an additional lateral tibial tunnel for PLMR repair, instead of the typically used single medial one, for PLMR repair during simultaneous revision ACL reconstruction.

IntroductionBacterial infection of the central nervous system (CNS) poses a clinical challenge and is a leading cause of neurological disorders in cattle. Human studies have demonstrated an increase in cerebrospinal fluid (CSF) L-lactate levels in bacterial meningitis. The aims of this study were to establish a Reference Interval (RI) for L-lactate in bovine CSF and assess its potential as a biomarker for detecting infectious-inflammatory disorders.MethodsCSF L-lactate was measured in the field using a commercially available lactate monitor. The RI for CSF L-lactate was calculated on healthy animals; univariate and receiver operating characteristic (ROC) analyses were performed to disclose an association between CSF L-lactate levels and interpretation of CSF in sick animals.ResultsTwenty-seven healthy cattle and 86 sick cattle with either CNS infectious-inflammatory disorders (47/86) or CNS disorders of other etiology (39/86) were included in this prospective study. The RI for CSF L-lactate was 1.1–2.4 mmol/L. The concentration was higher in the cattle with neutrophilic pleocytosis and the area under the ROC curve was 0.92 compared to other animals. Based on a cut-off of 3.15 mmol/L, CSF L-lactate had diagnostic sensitivity and specificity for neutrophilic pleocytosis of 93 and 80%, respectively.DiscussionThis is the first study to determine a RI for CSF L-lactate in cattle. Elevated CSF L-lactate levels indicated neutrophilic pleocytosis, which is often manifested in acute bacterial infection. The present findings may aid in diagnosis and correct use of antimicrobial drugs.

El estudiante que ingresa a la Educación Superior requiere manejar su conocimiento y aprendizaje de forma estratégica. En la medida en que este dispone de recursos metacognitivos para regular los procesos asociados al hecho de aprender, le permitirá tener mayor conciencia cognitiva. En esta investigación, se determinó el perfil metacognitivo de 532 estudiantes inscritos en el primer semestre de diferentes carreras que oferta la Universidad Nacional Experimental del Táchira, a través de las dimensiones que este constructo involucra: metamemoria, metalenguaje, metaatención y metacomprensión. Su identificación contribuye a conocer las necesidades diagnosticadas en los estudiantes, a fin de desarrollar nuevas estrategias de aprendizaje o fortalecer aquellas que conlleven a un proceso de formación integral de los futuros Ingenieros de la UNET. Los resultados indican que los estudiantes de nuevo ingreso presentan un perfil metacognitivo entre “moderado” y “alto”, por lo que se aprecia una adecuada habilidad metacognitiva para manejar y controlar el conocimiento que poseen.

Loss-, gain-of-function and mixed variants in SCN1A (Nav1.1 voltage-gated sodium channel) have been associated with a spectrum of neurologic disorders with different severity and drug-responsiveness. Most SCN1A variants are heterozygous changes occurring de novo or dominantly inherited; recessive inheritance has been reported in a few cases. Here, we report a family in which the biallelic inheritance of two novel SCN1A variants, N935Y and H1393Q, occurs in two siblings presenting with drug-responsive developmental and epileptic encephalopathy and born to heterozygous asymptomatic parents. To assess the genotype–phenotype correlation and support the treatment choice, HEK 293 cells were transfected with different combinations of the SCN1A WT and mutant cDNAs, and the resulting sodium currents were recorded through whole-cell patch-clamp. Functional studies showed that the N935Y and H1393Q channels and their combinations with the WT (WT + N935Y and WT + H1393Q) had current densities and biophysical properties comparable with those of their respective control conditions. This explains the asymptomatic condition of the probands’ parents. The co-expression of the N935Y + H1393Q channels, mimicking the recessive inheritance of the two variants in siblings, showed ~20% reduced current amplitude compared with WT and with parental channels. This mild loss of Nav1.1 function may contribute in part to the disease pathogenesis, although other mechanisms may be involved.

Somatostatin receptor ligands (SRLs) with high affinity for somatostatin receptors 2 and 5 (SSTR2 and SSTR5) are poorly efficacious in NF-PitNETs, expressing high levels of SSTR3. ITF2984 is a pan-SSTR ligand with high affinity for SSTR3, able to induce SSTR3 activation and to exert antitumoral activity in the MENX rat model. The aim of this study was to test ITF2984’s antiproliferative and proapoptotic effects in NF-PitNET primary cultured cells derived from surgically removed human tumors and to characterize their SSTR expression profile. We treated cells derived from 23 NF-PitNETs with ITF2984, and a subset of them with octreotide, pasireotide (SRLs with high affinity for SSTR2 or 5, respectively), or cabergoline (DRD2 agonist) and we measured cell proliferation and apoptosis. SSTR3, SSTR2, and SSTR5 expression in tumor tissues was analyzed by qRT-PCR and Western blot. We demonstrated that ITF2984 reduced cell proliferation (−40.8 (17.08)%, p < 0.001 vs. basal, n = 19 NF-PitNETs) and increased cell apoptosis (+41.4 (22.1)%, p < 0.001 vs. basal, n = 17 NF-PitNETs) in all tumors tested, whereas the other drugs were only effective in some tumors. In our model, SSTR3 expression levels did not correlate with ITF2984 antiproliferative nor proapoptotic effects. In conclusion, our data support a possible use of ITF2984 in the pharmacological treatment of NF-PitNET.

Introduction/Aims: Nusinersen intrathecal administration can be challenging in spinal muscular atrophy (SMA) adults. We aimed to determine if the ultrasound (US)‐assistance reduces the number of needle attempts and needle redirections needed for intrathecal drug administration and its impact on the procedure time, the incidence of adverse events (AEs), and patient satisfaction in these patients. Methods: Fifty‐eight patients aged 18 years and older scheduled for intrathecal nusinersen injection were enrolled and randomized (1:1 ratio) into Group 1 (nusinersen infusion with US‐assisted technique) or Group 2 (nusinersen infusion with landmark‐based technique). The number of attempts, number of redirections, periprocedural time, AEs and patient satisfaction were reported. Continuous variables were compared with the Student t‐test or Wilcoxon rank sum test. Categorical variables were evaluated with the Chi‐square test or Fisher's exact test in case of expected frequencies <5. The p‐values <.05 were considered statistically significant. Results: There were no statistical differences in the number of attempts, AEs, or patient satisfaction between the two groups. The number of needle redirections was significantly lower in the ultrasound group versus landmark‐based group (p <.05) in both the overall group of patients and in the subgroup with difficult spines. The periprocedural time was about 40 seconds longer in US‐group versus landmark‐based group (p <.05). Discussion: In SMA adults, US assistance reduces the number of needle redirections needed for intrathecal drug administration. These results suggest that the US assistance may be advantageous for nusinersen therapy to reduce the therapeutic burden of intrathecal infusion. [ABSTRACT FROM AUTHOR]

Introduction: Bacterial infection of the central nervous system (CNS) poses a clinical challenge and is a leading cause of neurological disorders in cattle. Human studies have demonstrated an increase in cerebrospinal fluid (CSF) L-lactate levels in bacterial meningitis. The aims of this study were to establish a Reference Interval (RI) for L-lactate in bovine CSF and assess its potential as a biomarker for detecting infectious-inflammatory disorders. Methods: CSF L-lactate was measured in the field using a commercially available lactate monitor. The RI for CSF L-lactate was calculated on healthy animals; univariate and receiver operating characteristic (ROC) analyses were performed to disclose an association between CSF L-lactate levels and interpretation of CSF in sick animals. Results: Twenty-seven healthy cattle and 86 sick cattle with either CNS infectiousinflammatory disorders (47/86) or CNS disorders of other etiology (39/86) were included in this prospective study. The RI for CSF L-lactate was 1.1-2.4 mmol/L. The concentration was higher in the cattle with neutrophilic pleocytosis and the area under the ROC curve was 0.92 compared to other animals. Based on a cut-off of 3.15 mmol/L, CSF L-lactate had diagnostic sensitivity and specificity for neutrophilic pleocytosis of 93 and 80%, respectively. Discussion: This is the first study to determine a RI for CSF L-lactate in cattle. Elevated CSF L-lactate levels indicated neutrophilic pleocytosis, which is often manifested in acute bacterial infection. The present findings may aid in diagnosis and correct use of antimicrobial drugs. [ABSTRACT FROM AUTHOR]

Background: Variability in obstetric outcomes in terms of the number and type of deliveries related to the day–night cycle has been described in previous studies. This 11-year retrospective analysis explores the effects of nighttime versus daytime delivery with labor epidural on obstetric outcomes. Methods: Data on deliveries performed between 1 October 2008 and 1 October 2019 were collected and differentiated into daytime, occurring from 8:00 a.m. to 7:59 p.m., and nighttime deliveries, occurring from 8:00 p.m. to 7:59 a.m. of the following day. The data collected included the patient history and maternal and neonatal outcomes. Results: A total of 29831 patients were included in the analysis. A positive and statistically significant correlation between the number of cesarean sections (Odds Ratio 1.35; 95% confidence interval = 1.26–1.44; p < 0.001) and the number of vaginal operative deliveries (Odds Ratio 1.21; 95% confidence interval = 1.01–1.44; p < 0.05) in patients who did not receive an epidural at nighttime was reported. Regarding the labor epidurals, a significantly greater incidence of accidental dural punctures with needles (0,4%; p < 0.05) in the nighttime versus daytime was reported. Conclusions: The absence of labor epidurals was associated with a significant increase in the number of cesarean sections and vaginal operative deliveries occurring at nighttime, without significant differences in labor duration. The incidence of anesthesiologic complications was greater in deliveries performed at nighttime. [ABSTRACT FROM AUTHOR]