Explosive activity of the summit cone of Piton de la Fournaise volcano (La Réunion island): A historical and geological review

International audienceSummit explosive activity and collapses that form pit craters and calderas represent major volcanic hazards on a dominantly effusive, frequently active volcano like Piton de la Fournaise. Only three summit collapse events (1986, 2002, 2007) have been recorded since the foundation of the Piton de la Fournaise volcano observatory (OVPF) in 1979, and two of them (1986 and 2007) were associated with weak phreatic activity. At Piton de la Fournaise, the normal explosive activity consists of short-lived and mild (< 20 m-high) lava fountains, which quickly evolve into strombolian activity during the eruptions. Based on comprehensive literature review and high-resolution image analysis of surface outcrops and summit caldera walls, we reconstructed the time distribution of recent explosive events (phreatomagmatic; phreatic) and their link with summit collapses and lateral (flank) effusive eruptions. In historical time (post-1640 CE), we recognise two main clusters of explosive events. Frequent and violent phreatomagmatic to phreatic explosions occurred during the oldest cluster (1708–1878) and alternated with long-lasting periods (years to decades) of summit effusive activity. In contrast, scarce, and on average, weak explosions occurred during the youngest cluster (1897–2012), when discrete and short-lived (< 6 months) effusive eruptions represent the main eruptive dynamics. Historical summit collapses (pit craters and caldera), all localised at the top of the summit cone, were related to voluminous lateral eruptions and were followed by a significant decrease in eruptive rate. However, magma draining during lateral eruptions was not systematically associated with summit collapses or explosions. The long-lasting occurrence of magma at very shallow depth below the volcano summit, followed by a rapid lateral drainage, apparently represents a critical condition favouring magma–groundwater interaction to produce explosive activity. The prehistoric growth of the Piton de la Fournaise summit cone results chiefly from long-lasting to continuous activity, centred below its western side (Bory crater containing lava lakes). High lava fountains, long-lasting effusive activity, lava lakes, ash plumes and block ejections were common types of eruptive dynamics in the historical past, between 1640 and 1878. In this perspective, short-lived, small volume eruptions and long pauses, up to six years, during the last century of activity of Piton de la Fournaise can be considered as a lull, despite the high frequency of eruption (1 eruption/9 months on average). Temporal and spatial variations in recurrence rate and eruptive dynamics of basaltic volcanism, such as those recognised at Piton de la Fournaise, should be considered in the formulation of hazard assessments and in the interpretation of precursory patterns

Verification, Analytical Validation, and Clinical Validation (V3): The Foundation of Determining Fit-for-Purpose for Biometric Monitoring Technologies (BioMeTs)

Digital medicine is an interdisciplinary field, drawing together stakeholders with expertize in engineering, manufacturing, clinical science, data science, biostatistics, regulatory science, ethics, patient advocacy, and healthcare policy, to name a few. Although this diversity is undoubtedly valuable, it can lead to confusion regarding terminology and best practices. There are many instances, as we detail in this paper, where a single term is used by different groups to mean different things, as well as cases where multiple terms are used to describe essentially the same concept. Our intent is to clarify core terminology and best practices for the evaluation of Biometric Monitoring Technologies (BioMeTs), without unnecessarily introducing new terms. We focus on the evaluation of BioMeTs as fit-for-purpose for use in clinical trials. However, our intent is for this framework to be instructional to all users of digital measurement tools, regardless of setting or intended use. We propose and describe a three-component framework intended to provide a foundational evaluation framework for BioMeTs. This framework includes (1) verification, (2) analytical validation, and (3) clinical validation. We aim for this common vocabulary to enable more effective communication and collaboration, generate a common and meaningful evidence base for BioMeTs, and improve the accessibility of the digital medicine field

An NMR‐based biosensor to measure stereo‐specific methionine sulfoxide reductase (MSR) activities in vitro and in vivo

Oxidation of protein methionines to methionine-sulfoxides (MetOx) is associated with several age-related diseases. In healthy cells, MetOx is reduced to methionine by two families of conserved methionine sulfoxide reductase enzymes, MSRA and MSRB that specifically target the S- or R-diastereoisomers of methionine-sulfoxides, respectively. To directly interrogate MSRA and MSRB functions in cellular settings, we developed an NMR-based biosensor that we call CarMetOx to simultaneously measure both enzyme activities in single reaction setups. We demonstrate the suitability of our strategy to delineate MSR functions in complex biological environments, including cell lysates and live zebrafish embryos. Thereby, we establish differences in substrate specificities between prokaryotic and eukaryotic MSRs and introduce CarMetOx as a highly sensitive tool for studying therapeutic targets of oxidative stress-related human diseases and redox regulated signaling pathways.Fil: Sanchez Lopez, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Labadie, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Lombardo, Veronica Andrea. Universidad Nacional de Rosario. Centro de Estudios Interdisciplinarios; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Biglione, Franco Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Manta, Bruno. Harvard Medical School; Estados UnidosFil: Jacob, Reeba. Weizmann Institute Of Science.; IsraelFil: Gladyshev, Vadim. Harvard Medical School; Estados UnidosFil: Abdelilah Seyfried, Salim. Universitat Potsdam; Alemania. Leibniz Universitat Hannover; AlemaniaFil: Selenko, Philipp. Weizmann Institute Of Science.; IsraelFil: Binolfi, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentin

Chronic constipation diagnosis and treatment evaluation: The "CHRO.CO.DI.T.E." study

Background: According to Rome criteria, chronic constipation (CC) includes functional constipation (FC) and irritable bowel syndrome with constipation (IBS-C). Some patients do not meet these criteria (No Rome Constipation, NRC). The aim of the study was is to evaluate the various clinical presentation and management of FC, IBS-C and NRC in Italy. Methods: During a 2-month period, 52 Italian gastroenterologists recorded clinical data of FC, IBS-C and NRC patients, using Bristol scale, PAC-SYM and PAC-QoL questionnaires. In addition, gastroenterologists were also asked to record whether the patients were clinically assessed for CC for the first time or were in follow up. Diagnostic tests and prescribed therapies were also recorded. Results: Eight hundred seventy-eight consecutive CC patients (706 F) were enrolled (FC 62.5%, IBS-C 31.3%, NRC 6.2%). PAC-SYM and PAC-QoL scores were higher in IBS-C than in FC and NRC. 49.5% were at their first gastroenterological evaluation for CC. In 48.5% CC duration was longer than 10 years. A specialist consultation was requested in 31.6%, more frequently in IBS-C than in NRC. Digital rectal examination was performed in only 56.4%. Diagnostic tests were prescribed to 80.0%. Faecal calprotectin, thyroid tests, celiac serology, breath tests were more frequently suggested in IBS-C and anorectal manometry in FC. More than 90% had at least one treatment suggested on chronic constipation, most frequently dietary changes, macrogol and fibers. Antispasmodics and psychotherapy were more frequently prescribed in IBS-C, prucalopride and pelvic floor rehabilitation in FC. Conclusions: Patients with IBS-C reported more severe symptoms and worse quality of life than FC and NRC. Digital rectal examination was often not performed but at least one diagnostic test was prescribed to most patients. Colonoscopy and blood tests were the "first line" diagnostic tools. Macrogol was the most prescribed laxative, and prucalopride and pelvic floor rehabilitation represented a "second line" approach. Diagnostic tests and prescribed therapies increased by increasing CC severity

Garbage in, garbage out: how reliable training data improved a virtual screening approach against SARS-CoV-2 MPro

Introduction: The identification of chemical compounds that interfere with SARS-CoV-2 replication continues to be a priority in several academic and pharmaceutical laboratories. Computational tools and approaches have the power to integrate, process and analyze multiple data in a short time. However, these initiatives may yield unrealistic results if the applied models are not inferred from reliable data and the resulting predictions are not confirmed by experimental evidence.Methods: We undertook a drug discovery campaign against the essential major protease (MPro) from SARS-CoV-2, which relied on an in silico search strategy –performed in a large and diverse chemolibrary– complemented by experimental validation. The computational method comprises a recently reported ligand-based approach developed upon refinement/learning cycles, and structure-based approximations. Search models were applied to both retrospective (in silico) and prospective (experimentally confirmed) screening.Results: The first generation of ligand-based models were fed by data, which to a great extent, had not been published in peer-reviewed articles. The first screening campaign performed with 188 compounds (46 in silico hits and 100 analogues, and 40 unrelated compounds: flavonols and pyrazoles) yielded three hits against MPro (IC50 ≤ 25 μM): two analogues of in silico hits (one glycoside and one benzo-thiazol) and one flavonol. A second generation of ligand-based models was developed based on this negative information and newly published peer-reviewed data for MPro inhibitors. This led to 43 new hit candidates belonging to different chemical families. From 45 compounds (28 in silico hits and 17 related analogues) tested in the second screening campaign, eight inhibited MPro with IC50 = 0.12–20 μM and five of them also impaired the proliferation of SARS-CoV-2 in Vero cells (EC50 7–45 μM).Discussion: Our study provides an example of a virtuous loop between computational and experimental approaches applied to target-focused drug discovery against a major and global pathogen, reaffirming the well-known “garbage in, garbage out” machine learning principle

Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)

The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical samples with examples of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer‐reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state‐of‐the‐art handbook for basic and clinical researchers.DFG, 389687267, Kompartimentalisierung, Aufrechterhaltung und Reaktivierung humaner Gedächtnis-T-Lymphozyten aus Knochenmark und peripherem BlutDFG, 80750187, SFB 841: Leberentzündungen: Infektion, Immunregulation und KonsequenzenEC/H2020/800924/EU/International Cancer Research Fellowships - 2/iCARE-2DFG, 252623821, Die Rolle von follikulären T-Helferzellen in T-Helferzell-Differenzierung, Funktion und PlastizitätDFG, 390873048, EXC 2151: ImmunoSensation2 - the immune sensory syste

A 5-year follow-up of general practice patients experiencing depression

Background. Depression is a common disease in primary care and produces significant morbidity in the community. Little is known about the outcomes of depression in general practice. Objectives. This research set out to explore both the longitudinal management and outcomes of depression as seen in general practice. Methods. The Medic-GP database is a collection of the medical records of >50 000 people seen in nine Australian general practices. It was used to follow the management of depressed patients over 4-5 years. Records from 1994-1995 were searched for depression or similar words. Individual records of patients whose notes mentioned depression were randomly selected and examined to determine if they were diagnosed with depression. Records of patients who were diagnosed as suffering from depression were examined to determine progress over the ensuing 5 years. Results. Six hundred of 5889 patients were examined in detail. A total of 382 patients (63.7%) were diagnosed with depression; 219 had been diagnosed during this time interval. The main findings were 64.7% of patients were female; 93.6% of patients received an antidepressant at some time during the study; 16% of patients were referred to a psychiatrist; 7.3% were hospitalized; 30% of patients who ceased antidepressants without a recurrence had courses of antidepressants of 3 months or less; and only 22.5% of patients had a single episode of depression. Conclusion. Unlike cross-sectional studies, this study has shown a high rate of prescription of antidepressants. GPs often prescribed short courses of antidepressants, and depression behaves as a chronic, recurrent disease

HR3DHG version 1: modeling the spatiotemporal dynamics of mercury in the Augusta Bay (southern Italy)

yyThe biogeochemical dynamics of Hg, and specifically of its three species Hg-0, Hg-II, and MeHg (elemental, inorganic, and organic, respectively), in the marine coastal area of Augusta Bay (southern Italy) have been explored by the high-resolution 3D Hg (HR3DHG) model, namely an advection-diffusion-reaction model for dissolved mercury in the seawater compartment coupled with a diffusion-reaction model for dissolved mercury in the pore water of sediments in which the desorption process for the sediment total mercury is taken into account. The spatiotemporal variability of the mercury concentration in both seawater ([Hg-D]) and the first layers of bottom sediments ([Hg-D(sed)] and [Hg-T(sed)]), as well as the Hg fluxes at the boundaries of the 3D model domain, have been theoretically reproduced, showing acceptable agreement with the experimental data collected in multiple field observations during six different oceanographic cruises. Also, the spatiotemporal dynamics of the total mercury concentration in seawater have been obtained by using both model results and field observations. The mass balance of the total Hg species in seawater has been calculated for the Augusta Harbour, improving previous estimations. The HR3DHG model could be used as an effective tool to predict the spatiotemporal distributions of dissolved and total mercury concentrations, while contributing to better assessing hazards for the environment and therefore for human health in highly polluted areas

Large-Scale Mercury Dispersion at Sea: Modelling a Multi-Hazard Case Study from Augusta Bay (Central Mediterranean Sea)

This contribution discusses an example of potential multi-hazard effects resulting from an earthquake in a highly seismogenic area of the Mediterranean Sea, the Augusta Bay, which presents high levels of contamination in sediments and seawater, due particularly to high-concentrations of mercury as a result of a long-term industrial exploitation. In particular, a high-resolution hydrodynamic and transport model is used to calculate the effects of enhanced mercury spreading in the open sea after significant damage and collapse of the artificial damming system confining the embayment where a very high concentration of Hg occurs in seafloor sediments and seawater. Coupling high-resolution 3D dynamic circulation modelling and sediment–seawater Hg fluxes calculated using the HR3DHG diffusion–reaction model for both inorganic and organic Hg species offers a valuable approach to simulating and estimating the effects of spatial dispersion of this contaminant due to unpredictable hazard events in coastal systems, with the potential attendant enhanced effects on the marine ecosystem. The simulated scenario definitely suggests that a combination of natural and anthropogenic multi-hazards calls for a thorough re-thinking of risk management in marine areas characterised by significant levels of contamination and where a deep understanding of the biogeochemical dynamics of pollutants does not cover all the aspects of danger for the environment

Eruptive activity of the summit cone of Piton de la Fournaise volcano (La Réunion island): a historical and geological review

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