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Sökning: WFRF:(Simone Roberto)

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1.
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2.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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3.
  • Abelev, Betty, et al. (författare)
  • Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
  • 2013
  • Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
  • Tidskriftsartikel (refereegranskat)abstract
    • Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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4.
  • Abelev, Betty, et al. (författare)
  • Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
  • 2012
  • Ingår i: Journal of High Energy Physics. - 1029-8479. ; :11
  • Tidskriftsartikel (refereegranskat)abstract
    • The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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5.
  • Abelev, Betty, et al. (författare)
  • Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
  • 2012
  • Ingår i: Journal of High Energy Physics. - 1029-8479. ; :7
  • Tidskriftsartikel (refereegranskat)abstract
    • We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
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6.
  • Ade, Peter, et al. (författare)
  • The Simons Observatory : science goals and forecasts
  • 2019
  • Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :2
  • Tidskriftsartikel (refereegranskat)abstract
    • The Simons Observatory (SO) is a new cosmic microwave background experiment being built on Cerro Toco in Chile, due to begin observations in the early 2020s. We describe the scientific goals of the experiment, motivate the design, and forecast its performance. SO will measure the temperature and polarization anisotropy of the cosmic microwave background in six frequency bands centered at: 27, 39, 93, 145, 225 and 280 GHz. The initial con figuration of SO will have three small-aperture 0.5-m telescopes and one large-aperture 6-m telescope, with a total of 60,000 cryogenic bolometers. Our key science goals are to characterize the primordial perturbations, measure the number of relativistic species and the mass of neutrinos, test for deviations from a cosmological constant, improve our understanding of galaxy evolution, and constrain the duration of reionization. The small aperture telescopes will target the largest angular scales observable from Chile, mapping approximate to 10% of the sky to a white noise level of 2 mu K-arcmin in combined 93 and 145 GHz bands, to measure the primordial tensor-to-scalar ratio, r, at a target level of sigma(r) = 0.003. The large aperture telescope will map approximate to 40% of the sky at arcminute angular resolution to an expected white noise level of 6 mu K-arcmin in combined 93 and 145 GHz bands, overlapping with the majority of the Large Synoptic Survey Telescope sky region and partially with the Dark Energy Spectroscopic Instrument. With up to an order of magnitude lower polarization noise than maps from the Planck satellite, the high-resolution sky maps will constrain cosmological parameters derived from the damping tail, gravitational lensing of the microwave background, the primordial bispectrum, and the thermal and kinematic Sunyaev-Zel'dovich effects, and will aid in delensing the large-angle polarization signal to measure the tensor-to-scalar ratio. The survey will also provide a legacy catalog of 16,000 galaxy clusters and more than 20,000 extragalactic sources.
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7.
  • DeAngelis, Nicola, et al. (författare)
  • 2020 WSES guidelines for the detection and management of bile duct injury during cholecystectomy
  • 2021
  • Ingår i: World Journal of Emergency Surgery. - : BMC. - 1749-7922. ; 16:1
  • Forskningsöversikt (refereegranskat)abstract
    • Bile duct injury (BDI) is a dangerous complication of cholecystectomy, with significant postoperative sequelae for the patient in terms of morbidity, mortality, and long-term quality of life. BDIs have an estimated incidence of 0.4-1.5%, but considering the number of cholecystectomies performed worldwide, mostly by laparoscopy, surgeons must be prepared to manage this surgical challenge. Most BDIs are recognized either during the procedure or in the immediate postoperative period. However, some BDIs may be discovered later during the postoperative period, and this may translate to delayed or inappropriate treatments. Providing a specific diagnosis and a precise description of the BDI will expedite the decision-making process and increase the chance of treatment success. Subsequently, the choice and timing of the appropriate reconstructive strategy have a critical role in long-term prognosis. Currently, a wide spectrum of multidisciplinary interventions with different degrees of invasiveness is indicated for BDI management. These World Society of Emergency Surgery (WSES) guidelines have been produced following an exhaustive review of the current literature and an international expert panel discussion with the aim of providing evidence-based recommendations to facilitate and standardize the detection and management of BDIs during cholecystectomy. In particular, the 2020 WSES guidelines cover the following key aspects: (1) strategies to minimize the risk of BDI during cholecystectomy; (2) BDI rates in general surgery units and review of surgical practice; (3) how to classify, stage, and report BDI once detected; (4) how to manage an intraoperatively detected BDI; (5) indications for antibiotic treatment; (6) indications for clinical, biochemical, and imaging investigations for suspected BDI; and (7) how to manage a postoperatively detected BDI.
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8.
  • Galosi, Serena, et al. (författare)
  • De novo DHDDS variants cause a neurodevelopmental and neurodegenerative disorder with myoclonus
  • 2022
  • Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 145:1, s. 208-223
  • Tidskriftsartikel (refereegranskat)abstract
    • Subcellular membrane systems are highly enriched in dolichol, whose role in organelle homeostasis and endosomal-lysosomal pathway remains largely unclear besides being involved in protein glycosylation. DHDDS encodes for the catalytic subunit (DHDDS) of the enzyme cis-prenyltransferase (cis-PTase), involved in dolichol biosynthesis and dolichol-dependent protein glycosylation in the endoplasmic reticulum. An autosomal recessive form of retinitis pigmentosa (retinitis pigmentosa 59) has been associated with a recurrent DHDDS variant. Moreover, two recurring de novo substitutions were detected in a few cases presenting with neurodevelopmental disorder, epilepsy, and movement disorder. We evaluated a large cohort of patients (n=25) with de novo pathogenic variants in DHDDS and provided the first systematic description of the clinical features and long-term outcome of this new neurodevelopmental and neurodegenerative disorder. The functional impact of the identified variants was explored by yeast complementation system and enzymatic assay. Patients presented during infancy or childhood with a variable association of neurodevelopmental disorder, generalized epilepsy, action myoclonus/cortical tremor, and ataxia. Later in the disease course they experienced a slow neurological decline with the emergence of hyperkinetic and/or hypokinetic movement disorder, cognitive deterioration, and psychiatric disturbances. Storage of lipidic material and altered lysosomes were detected in myelinated fibers and fibroblasts, suggesting a dysfunction of the lysosomal enzymatic scavenger machinery. Serum glycoprotein hypoglycosylation was not detected and, in contrast to retinitis pigmentosa and other congenital disorders of glycosylation involving dolichol metabolism, the urinary dolichol D18/D19 ratio was normal. Mapping the disease-causing variants into the protein structure revealed that most of them clustered around the active site of the DHDDS subunit. Functional studies using yeast complementation assay and in vitro activity measurements confirmed that these changes affected the catalytic activity of the cis-PTase and showed growth defect in yeast complementation system as compared with the wild-type enzyme and retinitis pigmentosa-associated protein. In conclusion, we characterized a distinctive neurodegenerative disorder due to de novo DHDDS variants, which clinically belongs to the spectrum of genetic progressive encephalopathies with myoclonus. Clinical and biochemical data from this cohort depicted a condition at the intersection of congenital disorders of glycosylation and inherited storage diseases with several features akin to of progressive myoclonus epilepsy such as neuronal ceroid lipofuscinosis and other lysosomal disorders.
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9.
  • Hibar, Derrek P., et al. (författare)
  • Novel genetic loci associated with hippocampal volume
  • 2017
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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10.
  • Jarvis, Debbie, et al. (författare)
  • Prevalence of asthma-like symptoms with ageing
  • 2018
  • Ingår i: Thorax. - : BMJ Publishing Group Ltd. - 0040-6376 .- 1468-3296. ; 73:1, s. 37-48
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Change in the prevalence of asthma-like symptoms in populations of ageing adults is likely to be influenced by smoking, asthma treatment and atopy.METHODS: The European Community Respiratory Health Survey collected information on prevalent asthma-like symptoms from representative samples of adults aged 20-44 years (29 centres in 13 European countries and Australia) at baseline and 10 and 20 years later (n=7844). Net changes in symptom prevalence were determined using generalised estimating equations (accounting for non-response through inverse probability weighting), followed by meta-analysis of centre level estimates.FINDINGS: Over 20 years the prevalence of 'wheeze' and 'wheeze in the absence of a cold' decreased (-2.4%, 95% CI -3.5 to -1.3%; -1.5%, 95% CI -2.4 to -0.6%, respectively) but the prevalence of asthma attacks, use of asthma medication and hay fever/nasal allergies increased (0.6%, 95% CI 0.1 to 1.11; 3.6%, 95% CI 3.0 to 4.2; 2.7%, 95% CI 1.7 to 3.7). Changes were similar in the first 10 years compared with the second 10 years, except for hay fever/nasal allergies (increase seen in the first 10 years only). Decreases in these wheeze-related symptoms were largely seen in the group who gave up smoking, and were seen in those who reported hay fever/nasal allergies at baseline.INTERPRETATION: European adults born between 1946 and 1970 have, over the last 20 years, experienced less wheeze, although they were more likely to report asthma attacks, use of asthma medication and hay fever. Decrease in wheeze is largely attributable to smoking cessation, rather than improved treatment of asthma. It may also be influenced by reductions in atopy with ageing.
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11.
  • Jones, Geraint H., et al. (författare)
  • The Comet Interceptor Mission
  • 2024
  • Ingår i: Space Science Reviews. - : Springer Nature. - 0038-6308 .- 1572-9672. ; 220:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Here we describe the novel, multi-point Comet Interceptor mission. It is dedicated to the exploration of a little-processed long-period comet, possibly entering the inner Solar System for the first time, or to encounter an interstellar object originating at another star. The objectives of the mission are to address the following questions: What are the surface composition, shape, morphology, and structure of the target object? What is the composition of the gas and dust in the coma, its connection to the nucleus, and the nature of its interaction with the solar wind? The mission was proposed to the European Space Agency in 2018, and formally adopted by the agency in June 2022, for launch in 2029 together with the Ariel mission. Comet Interceptor will take advantage of the opportunity presented by ESA’s F-Class call for fast, flexible, low-cost missions to which it was proposed. The call required a launch to a halo orbit around the Sun-Earth L2 point. The mission can take advantage of this placement to wait for the discovery of a suitable comet reachable with its minimum Δ V capability of 600 ms − 1 . Comet Interceptor will be unique in encountering and studying, at a nominal closest approach distance of 1000 km, a comet that represents a near-pristine sample of material from the formation of the Solar System. It will also add a capability that no previous cometary mission has had, which is to deploy two sub-probes – B1, provided by the Japanese space agency, JAXA, and B2 – that will follow different trajectories through the coma. While the main probe passes at a nominal 1000 km distance, probes B1 and B2 will follow different chords through the coma at distances of 850 km and 400 km, respectively. The result will be unique, simultaneous, spatially resolved information of the 3-dimensional properties of the target comet and its interaction with the space environment. We present the mission’s science background leading to these objectives, as well as an overview of the scientific instruments, mission design, and schedule.
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12.
  • Kourousias, George, et al. (författare)
  • Compressive Sensing for Dynamic XRF Scanning
  • 2020
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • X-Ray Fluorescence (XRF) scanning is a widespread technique of high importance and impact since it provides chemical composition maps crucial for several scientific investigations. There are continuous requirements for larger, faster and highly resolved acquisitions in order to study complex structures. Among the scientific applications that benefit from it, some of them, such as wide scale brain imaging, are prohibitively difficult due to time constraints. However, typically the overall XRF imaging performance is improving through technological progress on XRF detectors and X-ray sources. This paper suggests an additional approach where XRF scanning is performed in a sparse way by skipping specific points or by varying dynamically acquisition time or other scan settings in a conditional manner. This paves the way for Compressive Sensing in XRF scans where data are acquired in a reduced manner allowing for challenging experiments, currently not feasible with the traditional scanning strategies. A series of different compressive sensing strategies for dynamic scans are presented here. A proof of principle experiment was performed at the TwinMic beamline of Elettra synchrotron. The outcome demonstrates the potential of Compressive Sensing for dynamic scans, suggesting its use in challenging scientific experiments while proposing a technical solution for beamline acquisition software.
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13.
  • Satizabal, Claudia L., et al. (författare)
  • Genetic architecture of subcortical brain structures in 38,851 individuals
  • 2019
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
  • Tidskriftsartikel (refereegranskat)abstract
    • Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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14.
  • Smith, Annabel L., et al. (författare)
  • Global gene flow releases invasive plants from environmental constraints on genetic diversity
  • 2020
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 117:8, s. 4218-4227
  • Tidskriftsartikel (refereegranskat)abstract
    • When plants establish outside their native range, their ability to adapt to the new environment is influenced by both demography and dispersal. However, the relative importance of these two factors is poorly understood. To quantify the influence of demography and dispersal on patterns of genetic diversity underlying adaptation, we used data from a globally distributed demographic research network comprising 35 native and 18 nonnative populations of Plantago lanceolata. Species-specific simulation experiments showed that dispersal would dilute demographic influences on genetic diversity at local scales. Populations in the native European range had strong spatial genetic structure associated with geographic distance and precipitation seasonality. In contrast, nonnative populations had weaker spatial genetic structure that was not associated with environmental gradients but with higher within-population genetic diversity. Our findings show that dispersal caused by repeated, long-distance, human-mediated introductions has allowed invasive plant populations to overcome environmental constraints on genetic diversity, even without strong demographic changes. The impact of invasive plants may, therefore, increase with repeated introductions, highlighting the need to constrain future introductions of species even if they already exist in an area.
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15.
  • Aarrestad, Thea, et al. (författare)
  • Benchmark data and model independent event classification for the large hadron collider
  • 2022
  • Ingår i: SciPost Physics. - 2542-4653. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We describe the outcome of a data challenge conducted as part of the Dark Machines (https://www.darkmachines.org) initiative and the Les Houches 2019 workshop on Physics at TeV colliders. The challenged aims to detect signals of new physics at the Large Hadron Collider (LHC) using unsupervised machine learning algorithms. First, we propose how an anomaly score could be implemented to define model-independent signal regions in LHC searches. We define and describe a large benchmark dataset, consisting of > 1 billion simulated LHC events corresponding to 10 fb−1 of proton-proton collisions at a center-of-mass energy of 13 TeV. We then review a wide range of anomaly detection and density estimation algorithms, developed in the context of the data challenge, and we measure their performance in a set of realistic analysis environments. We draw a number of useful conclusions that will aid the development of unsupervised new physics searches during the third run of the LHC, and provide our benchmark dataset for future studies at https://www.phenoMLdata.org. Code to reproduce the analysis is provided at https://github.com/bostdiek/DarkMachines-UnsupervisedChallenge.
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16.
  • Accordini, Simone, et al. (författare)
  • The Cost of Persistent Asthma in Europe : An International Population-Based Study in Adults
  • 2013
  • Ingår i: International Archives of Allergy and Immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 160:1, s. 93-101
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: This study is aimed at providing a real-world evaluation of the economic cost of persistent asthma among European adults according to the degree of disease control [as defined by the 2006 Global Initiative for Asthma (GINA) guidelines]. Methods: A prevalence-based cost-of-illness study was carried out on 462 patients aged 30-54 years with persistent asthma (according to the 2002 GINA definition), who were identified in general population samples from 11 European countries and examined in clinical settings in the European Community Respiratory Health Survey II between 1999 and 2002. The cost estimates were computed from the societal perspective following the bottom-up approach on the basis of rates, wages and prices in 2004 (obtained at the national level from official sources), and were then converted to the 2010 values. Results: The mean total cost per patient was EUR 1,583 and was largely driven by indirect costs (i.e. lost working days and days with limited, not work-related activities 62.5%). The expected total cost in the population aged 30-54 years of the 11 European countries was EUR 4.3 billion (EUR 19.3 billion when extended to the whole European population aged from 15 to 64 years). The mean total cost per patient ranged from EUR 509 (controlled asthma) to EUR 2,281 (uncontrolled disease). Chronic cough or phlegm and having a high BMI significantly increased the individual total cost. Conclusions: Among European adults, the cost of persistent asthma drastically increases as disease control decreases. Therefore, substantial cost savings could be obtained through the proper management of adult patients in Europe.
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17.
  • Aguzzi, Jacopo, et al. (författare)
  • Developing technological synergies between deep-sea and space research
  • 2022
  • Ingår i: Elementa. - 2325-1026. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent advances in robotic design, autonomy and sensor integration create solutions for the exploration of deep-sea environments, transferable to the oceans of icy moons. Marine platforms do not yet have the mission autonomy capacity of their space counterparts (e.g., the state of the art Mars Perseverance rover mission), although different levels of autonomous navigation and mapping, as well as sampling, are an extant capability. In this setting their increasingly biomimicked designs may allow access to complex environmental scenarios, with novel, highly-integrated life-detecting, oceanographic and geochemical sensor packages. Here, we lay an outlook for the upcoming advances in deep-sea robotics through synergies with space technologies within three major research areas: biomimetic structure and propulsion (including power storage and generation), artificial intelligence and cooperative networks, and life-detecting instrument design. New morphological and material designs, with miniaturized and more diffuse sensor packages, will advance robotic sensing systems. Artificial intelligence algorithms controlling navigation and communications will allow the further development of the behavioral biomimicking by cooperating networks. Solutions will have to be tested within infrastructural networks of cabled observatories, neutrino telescopes, and off-shore industry sites with agendas and modalities that are beyond the scope of our work, but could draw inspiration on the proposed examples for the operational combination of fixed and mobile platforms.
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18.
  • Backes, Claudia, et al. (författare)
  • Production and processing of graphene and related materials
  • 2020
  • Ingår i: 2D Materials. - : IOP Publishing. - 2053-1583. ; 7:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present an overview of the main techniques for production and processing of graphene and related materials (GRMs), as well as the key characterization procedures. We adopt a 'hands-on' approach, providing practical details and procedures as derived from literature as well as from the authors' experience, in order to enable the reader to reproduce the results. Section I is devoted to 'bottom up' approaches, whereby individual constituents are pieced together into more complex structures. We consider graphene nanoribbons (GNRs) produced either by solution processing or by on-surface synthesis in ultra high vacuum (UHV), as well carbon nanomembranes (CNM). Production of a variety of GNRs with tailored band gaps and edge shapes is now possible. CNMs can be tuned in terms of porosity, crystallinity and electronic behaviour. Section II covers 'top down' techniques. These rely on breaking down of a layered precursor, in the graphene case usually natural crystals like graphite or artificially synthesized materials, such as highly oriented pyrolythic graphite, monolayers or few layers (FL) flakes. The main focus of this section is on various exfoliation techniques in a liquid media, either intercalation or liquid phase exfoliation (LPE). The choice of precursor, exfoliation method, medium as well as the control of parameters such as time or temperature are crucial. A definite choice of parameters and conditions yields a particular material with specific properties that makes it more suitable for a targeted application. We cover protocols for the graphitic precursors to graphene oxide (GO). This is an important material for a range of applications in biomedicine, energy storage, nanocomposites, etc. Hummers' and modified Hummers' methods are used to make GO that subsequently can be reduced to obtain reduced graphene oxide (RGO) with a variety of strategies. GO flakes are also employed to prepare three-dimensional (3d) low density structures, such as sponges, foams, hydro- or aerogels. The assembly of flakes into 3d structures can provide improved mechanical properties. Aerogels with a highly open structure, with interconnected hierarchical pores, can enhance the accessibility to the whole surface area, as relevant for a number of applications, such as energy storage. The main recipes to yield graphite intercalation compounds (GICs) are also discussed. GICs are suitable precursors for covalent functionalization of graphene, but can also be used for the synthesis of uncharged graphene in solution. Degradation of the molecules intercalated in GICs can be triggered by high temperature treatment or microwave irradiation, creating a gas pressure surge in graphite and exfoliation. Electrochemical exfoliation by applying a voltage in an electrolyte to a graphite electrode can be tuned by varying precursors, electrolytes and potential. Graphite electrodes can be either negatively or positively intercalated to obtain GICs that are subsequently exfoliated. We also discuss the materials that can be amenable to exfoliation, by employing a theoretical data-mining approach. The exfoliation of LMs usually results in a heterogeneous dispersion of flakes with different lateral size and thickness. This is a critical bottleneck for applications, and hinders the full exploitation of GRMs produced by solution processing. The establishment of procedures to control the morphological properties of exfoliated GRMs, which also need to be industrially scalable, is one of the key needs. Section III deals with the processing of flakes. (Ultra)centrifugation techniques have thus far been the most investigated to sort GRMs following ultrasonication, shear mixing, ball milling, microfluidization, and wet-jet milling. It allows sorting by size and thickness. Inks formulated from GRM dispersions can be printed using a number of processes, from inkjet to screen printing. Each technique has specific rheological requirements, as well as geometrical constraints. The solvent choice is critical, not only for the GRM stability, but also in terms of optimizing printing on different substrates, such as glass, Si, plastic, paper, etc, all with different surface energies. Chemical modifications of such substrates is also a key step. Sections IV-VII are devoted to the growth of GRMs on various substrates and their processing after growth to place them on the surface of choice for specific applications. The substrate for graphene growth is a key determinant of the nature and quality of the resultant film. The lattice mismatch between graphene and substrate influences the resulting crystallinity. Growth on insulators, such as SiO2, typically results in films with small crystallites, whereas growth on the close-packed surfaces of metals yields highly crystalline films. Section IV outlines the growth of graphene on SiC substrates. This satisfies the requirements for electronic applications, with well-defined graphene-substrate interface, low trapped impurities and no need for transfer. It also allows graphene structures and devices to be measured directly on the growth substrate. The flatness of the substrate results in graphene with minimal strain and ripples on large areas, allowing spectroscopies and surface science to be performed. We also discuss the surface engineering by intercalation of the resulting graphene, its integration with Si-wafers and the production of nanostructures with the desired shape, with no need for patterning. Section V deals with chemical vapour deposition (CVD) onto various transition metals and on insulators. Growth on Ni results in graphitized polycrystalline films. While the thickness of these films can be optimized by controlling the deposition parameters, such as the type of hydrocarbon precursor and temperature, it is difficult to attain single layer graphene (SLG) across large areas, owing to the simultaneous nucleation/growth and solution/precipitation mechanisms. The differing characteristics of polycrystalline Ni films facilitate the growth of graphitic layers at different rates, resulting in regions with differing numbers of graphitic layers. High-quality films can be grown on Cu. Cu is available in a variety of shapes and forms, such as foils, bulks, foams, thin films on other materials and powders, making it attractive for industrial production of large area graphene films. The push to use CVD graphene in applications has also triggered a research line for the direct growth on insulators. The quality of the resulting films is lower than possible to date on metals, but enough, in terms of transmittance and resistivity, for many applications as described in section V. Transfer technologies are the focus of section VI. CVD synthesis of graphene on metals and bottom up molecular approaches require SLG to be transferred to the final target substrates. To have technological impact, the advances in production of high-quality large-area CVD graphene must be commensurate with those on transfer and placement on the final substrates. This is a prerequisite for most applications, such as touch panels, anticorrosion coatings, transparent electrodes and gas sensors etc. New strategies have improved the transferred graphene quality, making CVD graphene a feasible option for CMOS foundries. Methods based on complete etching of the metal substrate in suitable etchants, typically iron chloride, ammonium persulfate, or hydrogen chloride although reliable, are time- and resource-consuming, with damage to graphene and production of metal and etchant residues. Electrochemical delamination in a low-concentration aqueous solution is an alternative. In this case metallic substrates can be reused. Dry transfer is less detrimental for the SLG quality, enabling a deterministic transfer. There is a large range of layered materials (LMs) beyond graphite. Only few of them have been already exfoliated and fully characterized. Section VII deals with the growth of some of these materials. Amongst them, h-BN, transition metal tri- and di-chalcogenides are of paramount importance. The growth of h-BN is at present considered essential for the development of graphene in (opto) electronic applications, as h-BN is ideal as capping layer or substrate. The interesting optical and electronic properties of TMDs also require the development of scalable methods for their production. Large scale growth using chemical/physical vapour deposition or thermal assisted conversion has been thus far limited to a small set, such as h-BN or some TMDs. Heterostructures could also be directly grown. Section VIII discusses advances in GRM functionalization. A broad range of organic molecules can be anchored to the sp(2) basal plane by reductive functionalization. Negatively charged graphene can be prepared in liquid phase (e.g. via intercalation chemistry or electrochemically) and can react with electrophiles. This can be achieved both in dispersion or on substrate. The functional groups of GO can be further derivatized. Graphene can also be noncovalently functionalized, in particular with polycyclic aromatic hydrocarbons that assemble on the sp(2) carbon network by pi-pi stacking. In the liquid phase, this can enhance the colloidal stability of SLG/FLG. Approaches to achieve noncovalent on-substrate functionalization are also discussed, which can chemically dope graphene. Research efforts to derivatize CNMs are also summarized, as well as novel routes to selectively address defect sites. In dispersion, edges are the most dominant defects and can be covalently modified. This enhances colloidal stability without modifying the graphene basal plane. Basal plane point defects can also be modified, passivated and healed in ultra-high vacuum. The decoration of graphene with metal nanoparticles (NPs) has also received considerable attention, as it allows to exploit synergistic effects between NPs and graphene. Decoration can be either achieved chemically or in the gas phase. All LMs,
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19.
  • Baldacci, Filippo, et al. (författare)
  • Two-level diagnostic classification using cerebrospinal fluid YKL-40 in Alzheimer's disease.
  • 2017
  • Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 13:9, s. 993-1003
  • Tidskriftsartikel (refereegranskat)abstract
    • We assessed the diagnostic accuracy of cerebrospinal fluid (CSF) YKL-40 in discriminating (1) clinical Alzheimer's disease (AD) from cognitively healthy controls (HCs) and frontotemporal dementia (FTD) (level I) and (2) patients stratified by different pathophysiological profiles from HCs and FTD following a novel unbiased/descriptive categorization based on CSF biomarkers, independent of cognitive impairment severity (level II).YKL-40 was compared among HCs (n=21), mild cognitive impairment (n=41), AD (n=35), and FTD (n=9) (level I) and among HCs (n=21), AD pathophysiology (tau and amyloid-β) negative (n=15), tau positive (n=15), amyloid-β positive (n=13), AD pathophysiology positive (n=33), and FTD (n=9) (level II).Level I: YKL-40 discriminated AD from HC and FTD (area under the receiver operating characteristic curves [AUROCs]=0.69, 0.71). Level II: YKL-40 discriminated tau-positive individuals and AD pathophysiology-positive individuals from HC, AD pathophysiology-positive patients from FTD (AUROCs=0.76, 0.72, 0.73).YKL-40 demonstrates fair performance in distinguishing tau-positive patients from HCs, suggesting it may aid clinical diagnosis and support a biomarker-guided pathophysiological stratification.
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20.
  • Baro, Simone, et al. (författare)
  • Modelling of a lined tyre for predicting cavity noise mitigation
  • 2019
  • Ingår i: Applied Acoustics. - : ELSEVIER SCI LTD. - 0003-682X .- 1872-910X. ; 155, s. 391-400
  • Tidskriftsartikel (refereegranskat)abstract
    • Tyre cavity resonance can significantly affect vehicle interior noise at frequencies around 200 Hz. The insertion of a sound absorbing liner inside the tyre is known to be an efficient countermeasure, in fact nowadays tyre manufacturers are already producing tyres implementing this kind of solution. The present work, through analytical and numerical models, supported by material testing, provides a methodology for predicting the dag performance of a lined tyre, taking into account tyre/lining geometry and sound absorbing material properties. The results reported in the paper show that for fixed material characteristics, the attenuation of the cavity resonance is mostly influenced by the volume of the lining treatment. Moreover, the numerical model developed for discontinuous treatments, suggests that for fixed volume and material properties, the cavity resonance attenuation can be increased by choosing a proper layout. Elsevier Ltd. All rights reserved.
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21.
  • Beal, Jacob, et al. (författare)
  • Robust estimation of bacterial cell count from optical density
  • 2020
  • Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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22.
  • Bonnetain, Franck, et al. (författare)
  • Guidelines for time-to-event end-point definitions in trials for pancreatic cancer : Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials)
  • 2014
  • Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 50:17, s. 2983-2993
  • Forskningsöversikt (refereegranskat)abstract
    • Background: Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across trials, hampering comparison between them. The aim of the DATECAN (Definition for the Assessment of Time-to-event End-points in CANcer trials)-Pancreas project is to provide guidelines for standardised definition of time-to-event end-points in RCTs for pancreatic cancer. Methods: Time-to-event end-points currently used were identified from a literature review of pancreatic RCT trials (2006-2009). Academic research groups were contacted for participation in order to select clinicians and methodologists to participate in the pilot and scoring groups (>30 experts). A consensus was built after 2 rounds of the modified Delphi formal consensus approach with the Rand scoring methodology (range: 1-9). Results: For pancreatic cancer, 14 time to event end-points and 25 distinct event types applied to two settings (detectable disease and/or no detectable disease) were considered relevant and included in the questionnaire sent to 52 selected experts. Thirty experts answered both scoring rounds. A total of 204 events distributed over the 14 end-points were scored. After the first round, consensus was reached for 25 items; after the second consensus was reached for 156 items; and after the face-to-face meeting for 203 items. Conclusion: The formal consensus approach reached the elaboration of guidelines for standardised definitions of time-to-event end-points allowing cross-comparison of RCTs in pancreatic cancer.
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23.
  • Carsin, Anne-Elie, et al. (författare)
  • Physical activity and incidence of restrictive spirometry pattern in adults
  • 2018
  • Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 52
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Introduction: A restrictive spirometry pattern is associated with high morbidity and mortality. Whether regular physical activity (PA) protects against this pattern has never been studied.Objective: To assess if PA is associated with the development of restrictive pattern.Methods: Lung function and PA were assessed in the second and third follow-up of the ECRHS (n=2757, 39-67 years) and SAPALDIA (n=2610, 36-82 y) cohorts. Subjects with restrictive or obstructive pattern at baseline were excluded. We assessed the association of being active at baseline (defined as exercising vigorously >2-3 times/wk for >1 h) and restrictive pattern at follow-up (defined as a post-bronchodilator FEV1/FVC≥LLN and FVC<80% pred.) using modified Poisson regression, adjusting for age, sex, smoking and asthma. We explored the impact of adjusting for baseline FVC. Additionally, models were repeated stratified by BMI.Results: After 10 years follow-up, 3.7% and 2.8% of participants developed a restrictive pattern, in ECRHS and SAPALDIA respectively. In both cohorts, being physically active was associated with lower risk of a restrictive pattern (meta-analysed RR 0.65, 95% CI 0.47-0.89). This association was stronger in overweight (0.41, 0.23-0.75) and obese (0.42, 0.17-1.05) than in normal weight subjects, but was attenuated when adjusting for baseline FVC (0.77, 0.58-1.04).Conclusion: In two large European studies, adults who reported more PA were at lower risk of developing a restrictive spirometry pattern. Lung function at baseline seemed to explain part of the observed association, stressing the need of adequate method to take into account both horse-racing and regression-to-the-means effects.
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24.
  • Castiglione, Alessandro, 1976-, et al. (författare)
  • Correspondence Between Cognitive and Audiological Evaluations Among the Elderly : A Preliminary Report of an Audiological Screening Model of Subjects at Risk of Cognitive Decline With Slightto Moderate Hearing Loss
  • 2019
  • Ingår i: Frontiers in Neuroscience. - Lausanne : Frontiers Media S.A.. - 1662-4548 .- 1662-453X. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Epidemiological studies show increasing prevalence rates of cognitive decline and hearing loss with age, particularly after the age of 65 years. These conditions are reported to be associated, although conclusive evidence of causality and implications is lacking. Nevertheless, audiological and cognitive assessment among elderly people is a key target for comprehensive and multidisciplinary evaluation of the subject's frailty status. To evaluate the use of tools for identifying older adults at risk of hearing loss and cognitive decline and to compare skills and abilities in terms of hearing and cognitive performances between older adults and young subjects, we performed a prospective cross-sectional study using supraliminal auditory tests. The relationship between cognitive assessment results and audiometric results was investigated, and reference ranges for different ages or stages of disease were determined. Patients older than 65 years with different degrees of hearing function were enrolled. Each subject underwent an extensive audiological assessment, including tonal and speech audiometry, Italian Matrix Sentence Test, and speech audiometry with logatomes in quiet. Cognitive function was screened and then verified by experienced clinicians using the Montreal Cognitive Assessment Score, the Geriatric Depression Scale, and further investigations in some. One hundred twenty-three subjects were finally enrolled during 2016-2019: 103 were >65 years of age and 20 were younger participants (as controls). Cognitive functions showed a correlation with the audiological results in post-lingual hearing-impaired patients, in particular in those affected by slight to moderate hearing loss and aged more than 70 years. Audiological testing can thus be useful in clinical assessment and identification of patients at risk of cognitive impairment. The study was limited by its sample size (CI 95%; CL 10%), strict dependence on language, and hearing threshold. Further investigations should be cond
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25.
  • Cazzoletti, Lucia, et al. (författare)
  • Asthma control in Europe : a real-world evaluation based on an international population-based study
  • 2007
  • Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 120:6, s. 1360-1367
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Epidemiologic evidence related to asthma control in   patients from the general population is scanty. Objectives: We sought to assess asthma control in several European   centers according to the Global Initiative for Asthma (GINA) guidelines   and to investigate its determinants. Methods: In the European Community Respiratory Health Survey 11   (1999-2002), 1241 adults with asthma were identified and classified   into inhaled corticosteroid (ICS) users and non-ICS users in the last   year. Control was assessed in both groups by using the GINA proposal   (controlled, partly controlled, and uncontrolled asthma), and it was   related to potential determinants. Results: Only 15% (95% CI, 12% to 19%) of subjects who had used ICSs in   the last year and 45% (95% CI, 41% to 50%) of non-ICS users had their   asthma under control; individuals with uncontrolled asthma accounted   for 49% (95% CI, 44% to 53%) and 18% (95% CI, 15% to 21%),   respectively. Among ICS users, the prevalence of uncontrolled asthma   showed great variability across Europe, ranging from 20% (95% CI, 7% to   41%; Iceland) to 67% (95% CI, 35% to 90%; Italy). Overweight status, chronic cough and phlegm, and sensitization to Cladosporium species   were associated with poor control in ICS users. About 65% and 87% of   ICS users with uncontrolled and partly controlled asthma, respectively,   were on a medication regimen that was less than recommended by the GINA   guidelines. Conclusion: Six of 7 European asthmatic adults using ICSs in the last   year did not achieve good disease control. The large majority of   subjects with poorly controlled asthma were using antiasthma drugs in a   suboptimal way. A wide variability in asthma control emerged across   Europe. Clinical implications: Greater attention should be paid to asthma management and to the implementation of the GINA guidelines.
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26.
  • Cazzoletti, Lucia, et al. (författare)
  • Asthma Severity According to Global Initiative for Asthma and Its Determinants : An International Study
  • 2010
  • Ingår i: International Archives of Allergy and Immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 151:1, s. 70-79
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The identification of the factors associated with severe asthma may shed some light on its etiology and on the mechanisms of its development. We aimed to describe asthma severity using the Global Initiative for Asthma (GINA) classification and to investigate its determinants in a cross-sectional, population-based sample in Europe. Methods: In the European Community Respiratory Health Survey II (1999-2002), 1,241 adults with asthma were identified. Severity was assessed using the 2002 GINA classification (intermittent, mild persistent, moderate persistent, severe persistent) and it was related to potential determinants by a multinomial logistic model, using the intermittent group as the reference category for relative risk ratios. Results: About 30% of asthmatic subjects were affected by moderate-to-severe asthma. Sensitization to Cladosporium was associated with a more than 5-fold greater risk of having (mild, moderate or severe) persistent asthma than intermittent asthma. Persistent asthma was positively associated with sensitization to house dust mite, nonseasonal asthma, an older age at asthma onset, and chronic cough and phlegm. Sensitization to cat increased the risk of severe asthma only. Smoking was more strongly associated with asthma severity in men, while rhinitis was more strongly associated with asthma severity in women. Conclusions: One third of the asthmatic population have moderate-to-severe asthma. Sensitization to perennial indoor allergens, particularly Cladosporium, is strongly associated with asthma severity. The role of smoking and rhinitis in determining asthma severity may differ between the sexes, and it should be further investigated. Copyright (C) 2009 S. Karger AG, Basel
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27.
  • Cerveri, Isa, et al. (författare)
  • The Impact of Cigarette Smoking on Asthma : A Population-Based International Cohort Study
  • 2012
  • Ingår i: International Archives of Allergy and Immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 158:2, s. 175-183
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The prevalence rates of smoking in subjects with asthma have frequently been reported as similar to those in the general population; however, available data are not up-to-date. There is only limited and somewhat conflicting information on the long-term effects of smoking on health outcomes among population-based cohorts of subjects with asthma. We aimed to investigate changes in smoking habits and their effects on forced expiratory volume in 1 s (FEV(1)) in subjects with asthma in comparison with the rest of the population, focusing on the healthy smoker effect. Methods: We studied 9,092 subjects without asthma and 1,045 with asthma at baseline who participated in both the European Community Respiratory Health Survey I (20-44 years old in 1991-1993) and II (1999-2002). Results: At follow-up, smoking was significantly less frequent among subjects with asthma than in the rest of the population (26 vs. 31%; p < 0.001). Subjects with asthma who were already ex-smokers at the beginning of the follow-up in the 1990s had the highest mean asthma score (number of reported asthma-like symptoms, range 0-5), probably as a result of the healthy smoker effect (2.80 vs. 2.44 in never smokers, 2.19 in quitters and 2.24 in smokers; p < 0.001). The influence of smoking on FEV(1) decline did not depend on asthma status. Smokers had the highest proportion of subjects with chronic cough/phlegm (p < 0.01). Conclusion: One out of 4 subjects with asthma continues smoking and reports significantly more chronic cough and phlegm than never smokers and ex-smokers. This stresses the importance of smoking cessation in all patients with asthma, even in those with less severe asthma.
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28.
  • Cerveri, Isa, et al. (författare)
  • Underestimation of airflow obstruction among young adults using FEV1/FVC<70% as a fixed cut-off : a longitudinal evaluation of clinical and functional outcomes
  • 2008
  • Ingår i: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 63:12, s. 1040-1045
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Early detection of airflow obstruction is particularly important among young adults because they are more likely to benefit from intervention. Using the forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) (FEV1/FVC) <70% fixed ratio, airflow obstruction may be underdiagnosed. The lower limit of normal (LLN), which is statistically defined by the lower fifth percentile of a reference population, is physiologically appropriate but it still needs a clinical validation.Methods: To evaluate the characteristics and longitudinal outcomes of subjects misidentified as normal by the fixed ratio with respect to the LLN, 6249 participants (aged 20-44 years) in the European Community Respiratory Health Survey were examined and divided into three groups (absence of airflow obstruction by the LLN and the fixed ratio; presence of airflow obstruction only by the LLN; presence of airflow obstruction by the two criteria) for 1991-1993. LLN equations were obtained from normal non-smoking participants. A set of clinical and functional outcomes was evaluated in 1999-2002.Results: The misidentified subjects were 318 (5.1%); only 45.6% of the subjects with airflow obstruction by the LLN were also identified by the fixed cut-off. At baseline, FEV1 (107%, 97%, 85%) progressively decreased and bronchial hyperresponsiveness (slope 7.84, 6.32, 5.57) progressively increased across the three groups. During follow-up, misidentified subjects had a significantly higher risk of developing chronic obstructive pulmonary disease and a significantly higher use of health resources (medicines, emergency department visits/hospital admissions) because of breathing problems than subjects without airflow obstruction (p<0.001).Conclusions: Our findings show the importance of using statistically derived spirometric criteria to identify airflow obstruction.
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29.
  • Ciccocioppo, Roberto, et al. (författare)
  • Stress-related neuropeptides and alcoholism : CRH, NPY, and beyond
  • 2009
  • Ingår i: Alcohol. - : Elsevier. - 0741-8329 .- 1873-6823. ; 43:7, s. 491-498
  • Tidskriftsartikel (refereegranskat)abstract
    • This article summarizes the proceedings of a symposium held at the conference on "Alcoholism and Stress: A Framework for Future Treatment Strategies" in Volterra, Italy, May 6-9, 2008. Chaired by Markus Heilig and Roberto Ciccocioppo, this symposium offered a forum for the presentation of recent data linking neuropetidergic neurotransmission to the regulation of different alcohol-related behaviors in animals and in humans. Dr. Donald Gehlert described the development of a new corticotrophin-releasing factor receptor 1 antagonist and showed its efficacy in reducing alcohol consumption and stress-induced relapse in different animal models of alcohol abuse. Dr. Andrey Ryabinin reviewed recent findings in his laboratory, indicating a role of the urocortin 1 receptor system in the regulation of alcohol intake. Dr. Annika Thorsell showed data supporting the significance of the neuropeptide Y receptor system in the modulation of behaviors associated with a history of ethanol intoxication. Dr. Roberto Ciccocioppo focused his presentation on the nociceptin/orphanin FQ (N/OFQ) receptors as treatment targets for alcoholism. Finally, Dr. Markus Heilig showed recent preclinical and clinical evidence suggesting that neurokinin 1 antagonism may represent a promising new treatment for alcoholism. Collectively, these investigators highlighted the significance of neuropeptidergic neurotransmission in the regulation of neurobiological mechanisms of alcohol addiction. Data also revealed the importance of these systems as treatment targets for the development of new medication for alcoholism.
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30.
  • Clima, Rosanna, et al. (författare)
  • HmtDB 2016 : data update, a better performing query system and human mitochondrial DNA haplogroup predictor
  • 2017
  • Ingår i: Nucleic Acids Research. - : Oxford University Press. - 0305-1048 .- 1362-4962. ; 45:D1, s. D698-D706
  • Tidskriftsartikel (refereegranskat)abstract
    • The HmtDB resource hosts a database of human mitochondrial genome sequences from individuals with healthy and disease phenotypes. The database is intended to support both population geneticists as well as clinicians undertaking the task to assess the pathogenicity of specific mtDNA mutations. The wide application of next-generation sequencing (NGS) has provided an enormous volume of high-resolution data at a low price, increasing the availability of human mitochondrial sequencing data, which called for a cogent and significant expansion of HmtDB data content that has more than tripled in the current release. We here describe additional novel features, including: (i) a complete, user-friendly restyling of the web interface, (ii) links to the command-line stand-alone and web versions of the MToolBox package, an up-to-date tool to reconstruct and analyze human mitochondrial DNA from NGS data and (iii) the implementation of the Reconstructed Sapiens Reference Sequence (RSRS) as mitochondrial reference sequence. The overall update renders HmtDB an even more handy and useful resource as it enables a more rapid data access, processing and analysis. HmtDB is accessible at http://www.hmtdb.uniba.it/.
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31.
  • Corsico, Angelo G, et al. (författare)
  • Factors affecting adherence to asthma treatment in an international cohort of young and middle-aged adults
  • 2007
  • Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 101:6, s. 1363-1367
  • Tidskriftsartikel (refereegranskat)abstract
    • Background A major reason of the poor control of asthma is that patients fail to adhere to their treatment. The aim of the study was to identify factors affecting changes in asthma treatment adherence in an international cohort. Methods A follow-up study was carried out by means of a structured clinical interview in 971 subjects with asthma from 12 countries who participated in both the European Community Respiratory Health Survey: ECRHS-I (1990–94) and ECRHS-II (1998–2002). Subjects were considered adherent if they reported they normally took all the prescribed drugs. A logistic model was used to study the adjusted effect of the determinants. Results The net change in adherence to anti-asthmatic treatment per 10 years of follow-up was −2% (95% CI: −9.5, 5.5), 7.5% (−2.6, 17.6), 15.0% (6.6, 23.5) and 19.8% (4.1, 35.5), respectively, in Nordic, Mediterranean, Continental and extra-European areas. Among the 428 non-adherent subjects in ECRHS-I, having regular consultations with health care professionals was the strongest predictor of increased adherence (OR 3.32; 95% CI: 1.08–10.17). Among the 543 adherent subjects in ECRHS-I, using inhaled corticosteroids significantly predicted a persistence of adherence (OR 2.04; 95% CI: 1.11–3.75). No effect of gender, age, duration of the disease, smoking habit and educational level was observed. Conclusions Our findings highlight the key role of doctors and nurses in educating and regularly reviewing the patients and support the efforts for an improvement of clinical communication.
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32.
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33.
  • de Marco, Roberto, et al. (författare)
  • Incidence of chronic obstructive pulmonary disease in a cohort of young adults according to the presence of chronic cough and phlegm
  • 2007
  • Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 175:1, s. 32-39
  • Tidskriftsartikel (refereegranskat)abstract
    • Rationale: The few prospective studies aimed at assessing the incidence of chronic obstructive pulmonary disease (COPD) in relation to the presence of chronic cough/phlegm have produced contrasting results. Objectives: To assess the incidence of COPD in a cohort of young adults and to test whether chronic cough/phlegm and dyspnea are independent predictors of COPD. Methods: An international cohort of 5,002 subjects without asthma (ages 20-44 yr) with normal lung function (FEV1/FVC ratio ≥ 70%) from 12 countries was followed from 1991-2002 in the frame of the European Community Respiratory Health Survey II. Incident cases of COPD were those who had an FEV 1/FVC ratio less than 70% at the end of the follow-up, but did not report having had a doctor diagnose asthma during the follow-up. Main Results: The incidence rate of COPD was 2.8 cases/1,000/yr (95% confidence interval [CI], 2.3-3.3). Chronic cough/phlegm was an independent and statistically significant predictor of COPD (incidence rate ratio [IRR], 1.85; 95% CI, 1.17-2.93) after adjusting for smoking habits and other potential confounders, whereas dyspnea was not associated with the disease (IRR = 0.98; 95% CI, 0.64-1.50). Subjects who reported chronic cough/phlegm both at baseline and at the follow-up had a nearly threefold-increased risk of developing COPD with respect to asymptomatic subjects (IRR = 2.88; 95% CI, 1.44-5.79). Conclusions: The incidence of COPD is substantial even in young adults. The presence of chronic cough/phlegm identifies a subgroup of subjects with a high risk of developing COPD, independently of smoking habits.
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34.
  • de Marco, Roberto, et al. (författare)
  • Inhaled steroids are associated with reduced lung function decline in subjects with asthma with elevated total IgE
  • 2007
  • Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 119:3, s. 611-617
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Few studies have investigated the long-term association between inhaled corticosteroids (ICSs) and lung function decline in asthma. OBJECTIVE: To evaluate whether prolonged treatment with ICSs is associated with FEV(1) decline in adults with asthma. METHODS: An international cohort of 667 subjects with asthma (20-44 years old) was identified in the European Community Respiratory Health Survey (1991-1993) and followed up from 1999 to 2002. Spirometry was performed on both occasions. FEV(1) decline was analyzed according to age, sex, height, body mass index, total IgE, time of ICS use, and smoking, while adjusting for potential confounders. RESULTS: As ICS use increased, the decline in FEV(1) was lower (P trend = .025): on average, decline passed from 34 mL/y in nonusers (half of the sample) to 20 mL/y in subjects treated for 48 months or more (18%). When adjusting for all covariates, there was an interaction (P = .02) between ICS use and total IgE: in subjects with high (>100 kU/L) IgE, ICS use for 4 years or more was associated with a lower FEV(1) decline (23 mL/y; 95% CI, 8-38 compared with nonusers). This association was not seen in those with lower IgE. CONCLUSION: Although confirming a beneficial long-term association between ICSs and lung function in asthma, our study suggests that subjects with high IgE could maximally benefit from a prolonged ICS treatment. CLINICAL IMPLICATIONS: This study adds further evidence to the beneficial effect of inhaled steroids on lung function in asthma; future studies will clarify whether calibrating the corticosteroid dose according to the level of total IgE is a feasible approach in asthma management.
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35.
  • de Marco, Roberto, et al. (författare)
  • Long-term outcomes in mild/moderate chronic obstructive pulmonary disease in the European community respiratory health survey
  • 2009
  • Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 180:10, s. 956-963
  • Tidskriftsartikel (refereegranskat)abstract
    • RATIONALE: Little is known about the long-term outcomes of individuals with mild/moderate chronic obstructive pulmonary disease (COPD) according to spirometric criteria. OBJECTIVES: To test whether nonsmokers and asymptomatic subjects with a spirometric diagnosis of COPD have a steeper decrease in lung function and higher hospitalization rates than subjects without airway obstruction. METHODS: A total of 5,205 subjects without asthma (20-44 years of age) from the general population, with FEV(1) >or= 50% predicted at baseline, were followed for 9 years in the frame of an international cohort study. Percent decrease in FEV(1) (DeltaFEV(1)%) and the annual hospitalization rate for respiratory causes during the follow-up were assessed for each subject. MEASUREMENTS AND MAIN RESULTS: At baseline, 324 (6.2%) subjects had the prebronchodilator FEV(1)/FVC ratio less than the lower limit of normal (LLN-COPD), and 105 (2.0%) subjects had the same ratio less than 0.70 (modified GOLD-COPD). At follow-up, smokers with LLN-COPD (n = 205) had a greater mean DeltaFEV(1)% (1.7%; 95% confidence interval [CI], 0.8-2.7) and a higher hospitalization rate (rate ratio [RR], 2.52; 95% CI, 1.65-3.86) than normal subjects. Similarly, symptomatic subjects with LLN-COPD (n = 104) had DeltaFEV(1)% (2.0%; 95% CI, 0.8-3.3) and the hospitalization rate (RR, 4.18; 95% CI, 2.43-7.21) higher than the reference group. By contrast, nonsmokers and asymptomatic subjects with LLN-COPD had outcomes that were similar or even better than normal subjects. Among subjects with LLN-COPD, the association of symptoms with DeltaFEV(1)% varied according to smoking habits (P = 0.007); it was particularly strong in symptomatic smokers and disappeared in symptomatic nonsmokers. Similar results were found with the modified GOLD classification. CONCLUSIONS: In relatively young populations, COPD is associated with poor long-term outcomes in smokers and in symptomatic subjects only.
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36.
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37.
  • de Marco, Roberto, et al. (författare)
  • Risk Factors for Chronic Obstructive Pulmonary Disease in a European Cohort of Young Adults
  • 2011
  • Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 183:7, s. 891-897
  • Tidskriftsartikel (refereegranskat)abstract
    • Rationale: Few studies have investigated the factors associated with the early inception of chronic obstructive pulmonary disease (COPD). Objectives: We investigated COPD risk factors in an international cohort of young adults using different spirometric definitions of the disease. Methods. We studied 4,636 subjects without asthma who had prebronchodilator FEV1/FVC measured in the European Community Respiratory Health Survey both in 1991 to 1993 (when they were 20-44 yr old) and in 1999 to 2002. COPD was defined according to the Global Initiative for Chronic Obstructive Lung Disease fixed cut-off criterion (FEV1/FVC < 0.70), and two criteria based on the Quanjer and LuftiBus reference equations (FEV1/FVC less than lower limit of normal). COPD determinants were studied using two-level Poisson regression models. Measurements and Main Results: COPD incidence ranged from 1.85 (lower limit of normal [Quanjer]) to 2.88 (Global Initiative for Chronic Obstructive Lung Disease) cases/1,000/yr. Although about half of the cases had smoked less than 20 pack-years, smoking was the main risk factor for COPD, and it accounted for 29 to 39% of the new cases during the follow-up. Airway hyperresponsiveness was the second strongest risk factor (15-17% of new cases). Other determinants were respiratory infections in childhood and a family history of asthma, whereas the role of sex, age, and of being underweight largely depended on the definition of COPD used. Conclusions: COPD may start early in life. Smoking prevention should be given the highest priority to reduce COPD occurrence. Airway hyperresponsiveness, a family history of asthma, and respiratory infections in childhood are other important determinants of COPD. We suggest the need for a definition of COPD that is not exclusively based on spirometry.
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38.
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39.
  • Dratva, Julia, et al. (författare)
  • Early Life Origins of Lung Ageing : Early Life Exposures and Lung Function Decline in Adulthood in Two European Cohorts Aged 28-73 Years
  • 2016
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Early life environment is essential for lung growth and maximally attained lung function. Whether early life exposures impact on lung function decline in adulthood, an indicator of lung ageing, has scarcely been studied. Methods Spirometry data from two time points (follow-up time 9-11 years) and information on early life exposures, health and life-style were available from 12862 persons aged 28-73 years participating in the European population-based cohorts SAPALDIA (n = 5705) and ECRHS (n = 7157). The associations of early life exposures with lung function (FEV1) decline were analysed using mixed-effects linear regression. Results Early life exposures were significantly associated with FEV1 decline, with estimates almost as large as personal smoking. FEV1 declined more rapidly among subjects born during the winter season (adjusted difference in FEV1/year of follow-up [95% CI] -2.04ml [-3.29;-0.80]), of older mothers, (-1.82 ml [-3.14;-0.49]) of smoking mothers (-1.82ml [-3.30;-0.34] or with younger siblings (-2.61ml [-3.85;-1.38]). Less rapid FEV1-decline was found in subjects who had attended daycare (3.98ml [2.78; 5.18]), and indicated in subjects with pets in childhood (0.97ml [-0.16; 2.09]). High maternal age and maternal smoking appeared to potentiate effects of personal smoking. The effects were independent of asthma at any age. Conclusion Early life factors predicted lung function decline decades later, suggesting that some mechanisms related lung ageing may be established early in life. Early life programming of susceptibility to adult insults could be a possible pathway that should be explored further.
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40.
  • Faramondi, Luca, et al. (författare)
  • A hybrid behavior- and Bayesian network-based framework for cyber–physical anomaly detection
  • 2023
  • Ingår i: Computers & electrical engineering. - 0045-7906 .- 1879-0755. ; 112
  • Tidskriftsartikel (refereegranskat)abstract
    • In recent years, the increasing Internet connectivity and heterogeneity of industrial protocols have been raising the number and nature of cyber-attacks against Industrial Control Systems (ICS). Such cyber-attacks may lead to cyber anomalies and further to the failure of physical components, thus leading to cyber–physical attacks. In this paper, we present a novel unsupervised cyber–physical anomaly detection framework based on a hybrid “multi-formalism” approach that combines the outcomes of multiple unsupervised behavior-based anomaly detectors through a Bayesian network-based probabilistic modeling of the ICS. More precisely, the framework consists of two behavior-based anomaly detection modules that monitor separately and simultaneously the behavior of cyber and physical data acquired from the ICS. The outputs of such modules are filtered and combined through a Bayesian network-based modeling in order to improve the trustworthiness of the detected anomalies and to provide the detection probability of cyber, physical, and cyber–physical anomalies, taking into account possible cascading effects over the cyber–physical process. The outcomes achieved through the implementation of our framework on the hardware-in-the-loop Water Distribution Testbed (WDT) dataset show very high detection performance with a strong ability to reject false positive events and to isolate and localize the anomalies over the cyber–physical process.
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41.
  • Fior, Simone, et al. (författare)
  • Spatiotemporal reconstruction of the Aquilegia rapid radiation through next-generation sequencing of rapidly evolving cpDNA regions.
  • 2013
  • Ingår i: The New phytologist. - : Wiley. - 1469-8137 .- 0028-646X. ; 198:2, s. 579-92
  • Tidskriftsartikel (refereegranskat)abstract
    • Aquilegia is a well-known model system in the field of evolutionary biology, but obtaining a resolved and well-supported phylogenetic reconstruction for the genus has been hindered by its recent and rapid diversification. Here, we applied 454 next-generation sequencing to PCR amplicons of 21 of the most rapidly evolving regions of the plastome to generate c. 24 kb of sequences from each of 84 individuals from throughout the genus. The resulting phylogeny has well-supported resolution of the main lineages of the genus, although recent diversification such as in the European taxa remains unresolved. By producing a chronogram of the whole Ranunculaceae family based on published data, we inferred calibration points for dating the Aquilegia radiation. The genus originated in the upper Miocene c. 6.9 million yr ago (Ma) in Eastern Asia, and diversification occurred c. 4.8 Ma with the split of two main clades, one colonizing North America, and the other Western Eurasia through the mountains of Central Asia. This was followed by a back-to-Asia migration, originating from the European stock using a North Asian route. These results provide the first backbone phylogeny and spatiotemporal reconstruction of the Aquilegia radiation, and constitute a robust framework to address the adaptative nature of speciation within the group.
  •  
42.
  • Forni, Claudia, et al. (författare)
  • Trabectedin (ET-743) promotes differentiation in myxoid liposarcoma tumors.
  • 2009
  • Ingår i: Molecular cancer therapeutics. - 1535-7163. ; 8:2, s. 449-57
  • Tidskriftsartikel (refereegranskat)abstract
    • Differentiation is a complex set of events that can be blocked by rearrangements of regulatory genes producing fusion proteins with altered properties. In the case of myxoid liposarcoma (MLS) tumors, the causative abnormality is a fusion between the CHOP transcription factor and the FUS or EWS genes. CHOP belongs to and is a negative regulator of the large CAAT/enhancer binding protein family whose alpha, beta, and delta members are master genes of adipogenesis. Recent clinical data indicate a peculiar sensitivity of these tumors to the natural marine compound trabectedin. One hypothesis is that the activity of trabectedin is related to the inactivation of the FUS-CHOP oncogene. We find that trabectedin causes detachment of the FUS-CHOP chimera from targeted promoters. Reverse transcription-PCR and chromatin immunoprecipitation analysis in a MLS line and surgical specimens of MLS patients in vivo show activation of the CAAT/enhancer binding protein-mediated transcriptional program that leads to morphologic changes of terminal adipogenesis. The activity is observed in cells with type 1 but not type 8 fusions. Hence, the drug induces maturation of MLS lipoblasts in vivo by targeting the FUS-CHOP-mediated transcriptional block. These data provide a rationale for the specific activity of trabectedin and open the perspective of combinatorial treatments with drugs acting on lipogenic pathways.
  •  
43.
  • Furberg, Helena, et al. (författare)
  • Genome-wide meta-analyses identify multiple loci associated with smoking behavior
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 134-441
  • Tidskriftsartikel (refereegranskat)abstract
    • Consistent but indirect evidence has implicated genetic factors in smoking behavior1,2. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], b = 1.03, standard error (s.e.) = 0.053, beta = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], b = 0.367, s. e. = 0.059, beta = 5.7 x 10(-10); and rs1028936[A], b = 0.446, s. e. = 0.074, beta = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], b = 0.333, s. e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation.
  •  
44.
  • Hampel, Harald, et al. (författare)
  • Alzheimer's disease biomarker-guided diagnostic workflow using the added value of six combined cerebrospinal fluid candidates: Aβ1-42, total-tau, phosphorylated-tau, NFL, neurogranin, and YKL-40.
  • 2018
  • Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 14:4, s. 492-501
  • Tidskriftsartikel (refereegranskat)abstract
    • The diagnostic and classificatory performances of all combinations of three core (amyloid β peptide [i.e., Aβ1-42], total tau [t-tau], and phosphorylated tau) and three novel (neurofilament light chain protein, neurogranin, and YKL-40) cerebrospinal fluid biomarkers of neurodegeneration were compared among individuals with mild cognitive impairment (n=41), Alzheimer's disease dementia (ADD; n=35), frontotemporal dementia (FTD; n=9), and cognitively healthy controls (HC; n=21), using 10-fold cross-validation.The combinations ranking in the top 10 according to diagnostic accuracy in differentiating between distinct diagnostic categories were identified.The single biomarkers or biomarker combinations generating the best area under the receiver operating characteristics (AUROCs) were the following: the combination [amyloid β peptide + phosphorylated tau+neurofilament light chain] for distinguishing between ADD patients and HC (AUROC=0.86), t-tau for distinguishing between ADD and FTD patients (AUROC=0.82), and t-tau for distinguishing between FTD patients and HC (AUROC=0.78).Novel and established cerebrospinal fluid markers perform with at least fair accuracy in the discrimination between ADD and FTD. The classification of mild cognitive impairment individuals was poor.
  •  
45.
  • Kehoe, Laura, et al. (författare)
  • Make EU trade with Brazil sustainable
  • 2019
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
  •  
46.
  • Khalid, Shahid, et al. (författare)
  • Structure-Property Correlations in Aqueous Binary Na + /K + -CH 3 COO - Highly Concentrated Electrolytes
  • 2023
  • Ingår i: Journal of Physical Chemistry C. - 1932-7447 .- 1932-7455. ; 127:20, s. 9823-9832
  • Tidskriftsartikel (refereegranskat)abstract
    • Highly concentrated aqueous binary solutions of acetate salts are promising systems for different electrochemical applications, for example, energy storage devices. The very high solubility of CH3COOK allows us to obtain water-in-salt electrolyte concentrations, thus reducing ion activity and extending the cathodic stability of an aqueous electrolyte. At the same time, the presence of Li+ or Na+ makes these solutions compatible with intercalation materials for the development of rechargeable alkaline-ion batteries. Although there is a growing interest in these systems, a fundamental understanding of their physicochemical properties is still lacking. Here, we report and discuss the physicochemical and electrochemical properties of a series of solutions based on 20 mol kg-1 CH3COOK with different concentrations of CH3COONa. The most concentrated solution, 20 mol kg-1 CH3COOK + 7 mol kg-1 CH3COONa, gives the best compromise between transport properties and electrochemical stability, displaying a conductivity of 21.2 mS cm-1 at 25 °C and a stability window of up to 3 V in “ideal” conditions, i.e., using a small surface area and highly electrocatalytic electrode in a flooded cell. Careful Raman spectroscopy analyses help to address the interaction network, the phase evolution with temperature, and the crystallization kinetics.
  •  
47.
  •  
48.
  • Kumar Maroju, Praveen, et al. (författare)
  • Attosecond pulse shaping using a seeded free-electron laser
  • 2020
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 578, s. 386-391
  • Tidskriftsartikel (refereegranskat)abstract
    • Attosecond pulses are central to the investigation of valence- and core-electron dynamics on their natural timescales. The reproducible generation and characterization of attosecond waveforms has been demonstrated so far only through the process of high-order harmonic generation. Several methods for shaping attosecond waveforms have been proposed, including the use of metallic filters, multilayer mirrors and manipulation of the driving field. However, none of these approaches allows the flexible manipulation of the temporal characteristics of the attosecond waveforms, and they suffer from the low conversion efficiency of the high-order harmonic generation process. Free-electron lasers, by contrast, deliver femtosecond, extreme-ultraviolet and X-ray pulses with energies ranging from tens of microjoules to a few millijoules. Recent experiments have shown that they can generate subfemtosecond spikes, but with temporal characteristics that change shot-to-shot. Here we report reproducible generation of high-energy (microjoule level) attosecond waveforms using a seeded free-electron laser. We demonstrate amplitude and phase manipulation of the harmonic components of an attosecond pulse train in combination with an approach for its temporal reconstruction. The results presented here open the way to performing attosecond time-resolved experiments with free-electron lasers.
  •  
49.
  • Landoni, Paolo, et al. (författare)
  • A taxonomy of competition-based approaches as innovation policy measures to foster external knowledge search
  • 2023
  • Ingår i: Journal of Knowledge Management. - : Emerald Publishing Limited. - 1758-7484 .- 1367-3270. ; 27:11, s. 136-156
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper aims to provide a comprehensive view of the different competition-based approaches that policymakers can exploit to foster external knowledge search and their positioning among innovation policy measures. A growing number of companies have implemented initiatives to access external knowledge to increase their innovativeness, consistently with the open innovation paradigm. Competition-based approaches have received increasing attention by the private sector as a way to access external knowledge. However, despite their potential role as innovation policy measures, a limited attention has been devoted so far to investigate them from the policymakers’ perspective. Design/methodology/approach: To this aim, a two-stage empirical analysis has been carried out to develop a taxonomy of competition-based approaches. The first stage leveraged a multiple case study methodology including a sample of 20 competition-based approaches, while the second one leveraged interviews with Italian and European key informants. Findings: This paper proposes a novel taxonomy including eight competition-based approaches, which differ among each other in terms of policy strategy, scope breadth and output required. Moreover, this paper enriches a well-established taxonomy of innovation policy instruments with the identified competition-based approaches. Originality/value: This study contributes to the current debate on innovation policy by providing a taxonomy that includes eight competition-based approaches that can be exploited by policymakers to foster external knowledge search as well as their positioning among the innovation policy instruments. The taxonomy will hopefully support policymakers in identifying of the most suitable instruments in the light of their policy strategy and objectives.
  •  
50.
  • Lista, Simone, et al. (författare)
  • Cerebrospinal Fluid Neurogranin as a Biomarker of Neurodegenerative Diseases: A Cross-Sectional Study.
  • 2017
  • Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908.
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated cerebrospinal fluid (CSF) concentrations of the postsynaptic biomarker neurogranin at baseline in cognitively healthy controls (HC) compared to individuals with mild cognitive impairment (MCI), patients with Alzheimer's disease (AD) dementia, and patients with frontotemporal dementia (FTD). CSF neurogranin was quantified using an in-house immunoassay in a cross-sectional multicenter study of 108 participants [AD dementia (n=35), FTD (n=9), MCI (n=41), cognitively HC (n=23)]. CSF neurogranin concentrations were significantly higher in AD patients compared with both HC subjects and FTD patients, suggesting that increased CSF neurogranin concentrations may indicate AD-related pathophysiology. CSF neurogranin was independently associated with both total tau and hyperphosphorylated tau proteins, whereas a non-significant correlation with the 42-amino acid-long amyloid-β peptide was evident. CSF neurogranin, however, was not superior to core AD biomarkers in differentiating HC from the three diagnostic groups, and it did not improve their diagnostic accuracy. We conclude that further classification and longitudinal studies are required to shed more light into the potential role of neurogranin as a pathophysiological biomarker of neurodegenerative diseases.
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