1,492 research outputs found

    A multi-scale risk assessment for tephra fallout and airborne concentration from multiple Icelandic volcanoes – Part 2: Vulnerability and impact

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    This is the final version of the article. Available from EGU via the DOI in this record.We perform a multi-scale impact assessment of tephra fallout and dispersal from explosive volcanic activity in Iceland. A companion paper (Biass et al., 2014; "A multi-scale risk assessment of tephra fallout and airborne concentration from multiple Icelandic volcanoes – Part I: hazard assessment") introduces a multi-scale probabilistic assessment of tephra hazard based on selected eruptive scenarios at four Icelandic volcanoes (Hekla, Askja, Eyjafjallajökull and Katla) and presents probabilistic hazard maps for tephra accumulation in Iceland and tephra dispersal across Europe. Here, we present the associated vulnerability and impact assessment that describes the importance of single features at national and European levels and considers several vulnerability indicators for tephra dispersal and deposition. At the national scale, we focus on physical, systemic and economic vulnerability of Iceland to tephra fallout, whereas at the European scale we focus on the systemic vulnerability of the air traffic system to tephra dispersal. This is the first vulnerability and impact assessment analysis of this type and, although it does not include all the aspects of physical and systemic vulnerability, it allows for identifying areas on which further specific analysis should be performed. Results include vulnerability maps for Iceland and European airspace and allow for the qualitative identification of the impacts at both scales in the case of an eruption occurring. Maps produced at the national scale show that tephra accumulation associated with all eruptive scenarios considered can disrupt the main electricity network, in particular in relation to an eruption of Askja. Results also show that several power plants would be affected if an eruption occurred at Hekla, Askja or Katla, causing a substantial systemic impact due to their importance for the Icelandic economy. Moreover, the Askja and Katla eruptive scenarios considered could have substantial impacts on agricultural activities (crops and pastures). At the European scale, eruptive scenarios at Askja and Katla are likely to affect European airspace, having substantial impacts, in particular, in the KeflavĂ­k and London flight information regions (FIRs), but also at FIRs above France, Germany and Scandinavia. Impacts would be particularly intense in the case of long-lasting activity at Katla. The occurrence of eruptive scenarios at Hekla is likely to produce high impacts at KeflavĂ­k FIR and London FIRs, and, in the case of higher magnitude, can also impact France's FIRs. Results could support land use and emergency planning at the national level and risk management strategies of the European air traffic system. Although we focus on Iceland, the proposed methodology could be applied to other active volcanic areas, enhancing the long-term tephra risk management. Moreover, the outcomes of this work pose the basis for quantitative analyses of expected impacts and their integration in a multi-risk framework.This work has been funded by the Spanish research project “Atmospheric transport models and massive parallelism: applications to volcanic ash clouds and dispersion of pollutants at an urban micro-scale” (ATMOST, CGL2009-10244) and the Fonds National Suisse project “Volcanic-Ash Dispersal from Selected Icelandic Volcanoes: Risk Assessment for the European Region” (IZK0Z2_142343). S. Biass is supported by SNF (#200021-129997) and ESF/MemoVolc (#5193) subsidies

    Untargeted NMR Metabolomics Reveals Alternative Biomarkers and Pathways in Alkaptonuria

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    Alkaptonuria (AKU) is an ultra-rare metabolic disease caused by the accumulation of homogentisic acid (HGA), an intermediate product of phenylalanine and tyrosine degradation. AKU patients carry variants within the gene coding for homogentisate-1,2-dioxygenase (HGD), which are responsible for reducing the enzyme catalytic activity and the consequent accumulation of HGA and formation of a dark pigment called the ochronotic pigment. In individuals with alkaptonuria, ochronotic pigmentation of connective tissues occurs, leading to inflammation, degeneration, and eventually osteoarthritis. The molecular mechanisms underlying the multisystemic development of the disease severity are still not fully understood and are mostly limited to the metabolic pathway segment involving HGA. In this view, untargeted metabolomics of biofluids in metabolic diseases allows the direct investigation of molecular species involved in pathways alterations and their interplay. Here, we present the untargeted metabolomics study of AKU through the nuclear magnetic resonance of urine from a cohort of Italian patients; the study aims to unravel molecular species and mechanisms underlying the AKU metabolic disorder. Dysregulation of metabolic pathways other than the HGD route and new potential biomarkers beyond homogentisate are suggested, contributing to a more comprehensive molecular signature definition for AKU and the development of future adjuvant treatment. © 2022 by the authors

    Proteomic and Biological Analysis of the Effects of Metformin Senomorphics on the Mesenchymal Stromal Cells

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    Senotherapeutics are new drugs that can modulate senescence phenomena within tissues and reduce the onset of age-related pathologies. Senotherapeutics are divided into senolytics and senomorphics. The senolytics selectively kill senescent cells, while the senomorphics delay or block the onset of senescence. Metformin has been used to treat diabetes for several decades. Recently, it has been proposed that metformin may have anti-aging properties as it prevents DNA damage and inflammation. We evaluated the senomorphic effect of 6 weeks of therapeutic metformin treatment on the biology of human adipose mesenchymal stromal cells (MSCs). The study was combined with a proteome analysis of changes occurring in MSCs’ intracellular and secretome protein composition in order to identify molecular pathways associated with the observed biological phenomena. The metformin reduced the replicative senescence and cell death phenomena associated with prolonged in vitro cultivation. The continuous metformin supplementation delayed and/or reduced the impairment of MSC functions as evidenced by the presence of three specific pathways in metformin-treated samples: 1) the alpha-adrenergic signaling, which contributes to regulation of MSCs physiological secretory activity, 2) the signaling pathway associated with MSCs detoxification activity, and 3) the aspartate degradation pathway for optimal energy production. The senomorphic function of metformin seemed related to its reactive oxygen species (ROS) scavenging activity. In metformin-treated samples, the CEBPA, TP53 and USF1 transcription factors appeared to be involved in the regulation of several factors (SOD1, SOD2, CAT, GLRX, GSTP1) blocking ROS

    Methodological framework for an integrated multi-scale vulnerability and resilience assessment

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    The deliverable illustrates the methodological framework to assess vulnerability and resilience across different temporal and spatial scales, acknowledging the different domains where the latter may manifest, and in particular in the natural and the built environment, allocating a large importance to the so called “critical infrastructures”, in social and economic systems. A set of four matrices has been developed to identify what aspects should be looked at before the impact, that is to say what shows the potential ability or inability to cope with an extreme; at the impact, addressing in particular the capacity (or incapacity) to sustain various types of stresses (in the form of acceleration, pressure, heat
); in the time immediately after the impact, as the ability (or inability) to suffer losses and still continue functioning; and in the longer term of recovery, as the capacity to find a new state of equilibrium in which the fragilities manifested during and after the impact are addressed. Developing the framework, a particular attention has been paid to the relationships among systems within the same matrix and among matrices, across spatial and temporal scales. A set of matrices has been developed for different natural hazards, including in particular landslides and floods, trying to include as much as possible what past cases, the international literature and prior experience of involved partners have indicated as relevant parameters and factors to look at. In this regard, the project builds on the state of the art, embedding what has been learned until now in terms of response capacity to a variety of stresses and in the meantime identifying gaps to be addressed by future research

    Is avolition in schizophrenia associated with a deficit of dorsal caudate activity? A functional magnetic resonance imaging study during reward anticipation and feedback

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    BACKGROUND: The neurobiological underpinnings of avolition in schizophrenia remain unclear. Most brain imaging research has focused on reward prediction deficit and on ventral striatum dysfunction, but findings are not consistent. In the light of accumulating evidence that both ventral striatum and dorsal caudate play a key role in motivation, we investigated ventral striatum and dorsal caudate activation during processing of reward or loss in patients with schizophrenia. METHOD: We used functional magnetic resonance imaging to study brain activation during a Monetary Incentive Delay task in patients with schizophrenia, treated with second-generation antipsychotics only, and in healthy controls (HC). We also assessed the relationships of ventral striatum and dorsal caudate activation with measures of hedonic experience and motivation. RESULTS: The whole patient group had lower motivation but comparable hedonic experience and striatal activation than HC. Patients with high avolition scores showed lower dorsal caudate activation than both HC and patients with low avolition scores. A lower dorsal caudate activation was also observed in patients with deficit schizophrenia compared to HC and patients with non-deficit schizophrenia. Dorsal caudate activity during reward anticipation was significantly associated with avolition, but not with anhedonia in the patient group. CONCLUSIONS: These findings suggest that avolition in schizophrenia is linked to dorsal caudate hypoactivation

    Relation between EEG source functional connectivity and the negative symptom severity in schizophrenia: a preliminary report from a multicentre study

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    IntroductionNeural dysconnectivity is hypothesized to be a key element in pathophysiology of schizophrenia. However, the relation of disordered connectivity with the different clinical characteristics of the syndrome is not fully elucidated.ObjectivesThe current research investigated the relations between resting-state EEG Source Functional Connectivity (EEG-SFC) and the two main clusters of negative symptoms derived from the Brief Negative Symptom Scale, the Expressive Deficit (ED) and the Avolition (AV), in subjects with schizophrenia (SCZ) enrolled to the multicentre study of the Italian Network for Research on Psychoses.MethodsOut of 97 chronic, stabilized SCZ included, we selected subjects according the lower and the upper quartile of the ED and AV value distribution: 25 were in upper and 24 in the lower quartile of ED (respectively, HIGH-ED and LOW-ED); 27 were in upper and 24 in the lower quartile of AV (respectively, HIGH-AV and LOW-AV). Fifty-five healthy controls (HC) were included, comparable to SCZ for gender, age and educational level. EEG-SFC analysis was based on the lagged phase synchronization (LPS) computed by eLORETA from 5 minutes resting-state EEG recordings in eyes closed condition. LPS indices were determined for each spectrum band and between all 28 regions of interest (ROI) pairs. Group differences were significant for corrected P-value &lt; 0.05.ResultsSCZ had higher theta band LPS than HC. Respect to LOW-ED, HIGH-ED showed significant increased alpha LPS in fronto-cingulate, para-hippocampal and insular inter-hemispheric ROI pairs. No significant difference emerged between HIGH-AV and LOW-AV.ConclusionsSubgrouping SCZ according to negative symptom severity reveals heterogeneous patterns of resting-state LPS connectivity.Disclosure of interestThe authors have not supplied their declaration of competing interest.</jats:sec

    Unmet needs in patients with first-episode schizophrenia: a longitudinal perspective

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    Background This study aimed to identify the course of unmet needs by patients with a first episode of schizophrenia and to determine associated variables. Method We investigated baseline assessments in the European First Episode Schizophrenia Trial (EUFEST) and also follow-up interviews at 6 and 12 months. Latent class growth analysis was used to identify patient groups based on individual differences in the development of unmet needs. Multinomial logistic regression determined the predictors of group membership. Results Four classes were identified. Three differed in their baseline levels of unmet needs whereas the fourth had a marked decrease in such needs. Main predictors of class membership were prognosis and depression at baseline, and the quality of life and psychosocial intervention at follow-up. Depression at follow-up did not vary among classes. Conclusions We identified subtypes of patients with different courses of unmet needs. Prognosis of clinical improvement was a better predictor for the decline in unmet needs than was psychopathology. Needs concerning social relationships were particularly persistent in patients who remained high in their unmet needs and who lacked additional psychosocial treatmen

    Improved cardiovascular diagnostic accuracy by pocket size imaging device in non-cardiologic outpatients: the NaUSiCa (Naples Ultrasound Stethoscope in Cardiology) study

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    Miniaturization has evolved in the creation of a pocket-size imaging device which can be utilized as an ultrasound stethoscope. This study assessed the additional diagnostic power of pocket size device by both experts operators and trainees in comparison with physical examination and its appropriateness of use in comparison with standard echo machine in a non-cardiologic population

    Vitamin d deficiency induces chronic pain and microglial phenotypic changes in mice

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    The bioactive form of vitamin .D, 1,25‐dihydroxyvitamin D (1,25D3), exerts immunomodulatory actions resulting in neuroprotective effects potentially useful against neurodegenerative and autoimmune diseases. In fact, vitamin D deficiency status has been correlated with painful manifestations associated with different pathological conditions. In this study, we have investigated the effects of vitamin D deficiency on microglia cells, as they represent the main immune cells responsible for early defense at central nervous system (CNS), including chronic pain states. For this purpose, we have employed a model of low vitamin D intake during gestation to evaluate possible changes in primary microglia cells obtained from postnatal day(P)2‐ 3 pups. Afterwards, pain measurement and microglia morphological analysis in the spinal cord level and in brain regions involved in the integration of pain perception were performed in the parents subjected to vitamin D restriction. In cultured microglia, we detected a reactive—activated and proliferative—phenotype associated with intracellular reactive oxygen species (ROS) generation. Oxidative stress was closely correlated with the extent of DNA damage and increased ÎČ‐galactosidase (B‐gal) activity. Interestingly, the incubation with 25D3 or 1,25D3 or palmitoylethanolamide, an endogenous ligand of peroxisome proliferator‐activated‐receptor‐alpha (PPAR‐α), reduced most of these effects. Morphological analysis of ex‐vivo microglia obtained from vitamin‐D‐deficient adult mice revealed an increased number of activated microglia in the spinal cord, while in the brain microglia appeared in a dystrophic phenotype. Remarkably, activated (spinal) or dystrophic (brain) microglia were detected in a prominent manner in females. Our data indicate that vitamin D deficiency produces profound modifications in microglia, suggesting a possible role of these cells in the sensorial dysfunctions associated with hypovitaminosis D
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