| 1. |
- Bombarda, F., et al.
(author)
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Runaway electron beam control
- 2019
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In: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 1361-6587 .- 0741-3335. ; 61:1
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Journal article (peer-reviewed)
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| 2. |
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- 2018
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In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 58:1
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Research review (peer-reviewed)
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| 7. |
- Joffrin, E., et al.
(author)
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Overview of the JET preparation for deuterium-tritium operation with the ITER like-wall
- 2019
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In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
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Research review (peer-reviewed)abstract
- For the past several years, the JET scientific programme (Pamela et al 2007 Fusion Eng. Des. 82 590) has been engaged in a multi-campaign effort, including experiments in D, H and T, leading up to 2020 and the first experiments with 50%/50% D-T mixtures since 1997 and the first ever D-T plasmas with the ITER mix of plasma-facing component materials. For this purpose, a concerted physics and technology programme was launched with a view to prepare the D-T campaign (DTE2). This paper addresses the key elements developed by the JET programme directly contributing to the D-T preparation. This intense preparation includes the review of the physics basis for the D-T operational scenarios, including the fusion power predictions through first principle and integrated modelling, and the impact of isotopes in the operation and physics of D-T plasmas (thermal and particle transport, high confinement mode (H-mode) access, Be and W erosion, fuel recovery, etc). This effort also requires improving several aspects of plasma operation for DTE2, such as real time control schemes, heat load control, disruption avoidance and a mitigation system (including the installation of a new shattered pellet injector), novel ion cyclotron resonance heating schemes (such as the three-ions scheme), new diagnostics (neutron camera and spectrometer, active Alfven eigenmode antennas, neutral gauges, radiation hard imaging systems...) and the calibration of the JET neutron diagnostics at 14 MeV for accurate fusion power measurement. The active preparation of JET for the 2020 D-T campaign provides an incomparable source of information and a basis for the future D-T operation of ITER, and it is also foreseen that a large number of key physics issues will be addressed in support of burning plasmas.
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| 24. |
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- 2018
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In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 58:9
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Journal article (peer-reviewed)
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| 25. |
- Loza, M. J., et al.
(author)
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Validated and longitudinally stable asthma phenotypes based on cluster analysis of the ADEPT study
- 2016
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In: Respiratory Research. - : Springer Nature. - 1465-9921 .- 1465-993X. ; 17:1
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Journal article (peer-reviewed)abstract
- Background: Asthma is a disease of varying severity and differing disease mechanisms. To date, studies aimed at stratifying asthma into clinically useful phenotypes have produced a number of phenotypes that have yet to be assessed for stability and to be validated in independent cohorts. The aim of this study was to define and validate, for the first time ever, clinically driven asthma phenotypes using two independent, severe asthma cohorts: ADEPT and U-BIOPRED. Methods: Fuzzy partition-around-medoid clustering was performed on pre-specified data from the ADEPT participants (n = 156) and independently on data from a subset of U-BIOPRED asthma participants (n = 82) for whom the same variables were available. Models for cluster classification probabilities were derived and applied to the 12-month longitudinal ADEPT data and to a larger subset of the U-BIOPRED asthma dataset (n = 397). High and low type-2 inflammation phenotypes were defined as high or low Th2 activity, indicated by endobronchial biopsies gene expression changes downstream of IL-4 or IL-13. Results: Four phenotypes were identified in the ADEPT (training) cohort, with distinct clinical and biomarker profiles. Phenotype 1 was "mild, good lung function, early onset", with a low-inflammatory, predominantly Type-2, phenotype. Phenotype 2 had a "moderate, hyper-responsive, eosinophilic" phenotype, with moderate asthma control, mild airflow obstruction and predominant Type-2 inflammation. Phenotype 3 had a "mixed severity, predominantly fixed obstructive, non-eosinophilic and neutrophilic" phenotype, with moderate asthma control and low Type-2 inflammation. Phenotype 4 had a "severe uncontrolled, severe reversible obstruction, mixed granulocytic" phenotype, with moderate Type-2 inflammation. These phenotypes had good longitudinal stability in the ADEPT cohort. They were reproduced and demonstrated high classification probability in two subsets of the U-BIOPRED asthma cohort. Conclusions: Focusing on the biology of the four clinical independently-validated easy-to-assess ADEPT asthma phenotypes will help understanding the unmet need and will aid in developing tailored therapies. Trial registration:NCT01274507(ADEPT), registered October 28, 2010 and NCT01982162(U-BIOPRED), registered October 30, 2013.
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| 26. |
- Litaudon, X., et al.
(author)
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14 MeV calibration of JET neutron detectors-phase 1: Calibration and characterization of the neutron source
- 2018
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In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 58:2
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Journal article (peer-reviewed)abstract
- In view of the planned DT operations at JET, a calibration of the JET neutron monitors at 14 MeV neutron energy is needed using a 14 MeV neutron generator deployed inside the vacuum vessel by the JET remote handling system. The target accuracy of this calibration is 10% as also required by ITER, where a precise neutron yield measurement is important, e.g. for tritium accountancy. To achieve this accuracy, the 14 MeV neutron generator selected as the calibration source has been fully characterised and calibrated prior to the in-vessel calibration of the JET monitors. This paper describes the measurements performed using different types of neutron detectors, spectrometers, calibrated long counters and activation foils which allowed us to obtain the neutron emission rate and the anisotropy of the neutron generator, i.e.The neutron flux and energy spectrum dependence on emission angle, and to derive the absolute emission rate in 4π sr. The use of high resolution diamond spectrometers made it possible to resolve the complex features of the neutron energy spectra resulting from the mixed D/T beam ions reacting with the D/T nuclei present in the neutron generator target. As the neutron generator is not a stable neutron source, several monitoring detectors were attached to it by means of an ad hoc mechanical structure to continuously monitor the neutron emission rate during the in-vessel calibration. These monitoring detectors, two diamond diodes and activation foils, have been calibrated in terms of neutrons/counts within ± 5% total uncertainty. A neutron source routine has been developed, able to produce the neutron spectra resulting from all possible reactions occurring with the D/T ions in the beam impinging on the Ti D/T target. The neutron energy spectra calculated by combining the source routine with a MCNP model of the neutron generator have been validated by the measurements. These numerical tools will be key in analysing the results from the in-vessel calibration and to derive the response of the JET neutron detectors to DT plasma neutrons starting from the response to the generator neutrons, and taking into account all the calibration circumstances.
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| 27. |
- Hou, Liping, et al.
(author)
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Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder.
- 2016
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In: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:15, s. 3383-94
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Journal article (peer-reviewed)abstract
- Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ∼2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, p=5.87×10(-9); odds ratio=1.12) and markers within ERBB2 (rs2517959, p=4.53×10(-9); odds ratio=1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.
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| 28. |
- Debette, Stéphanie, et al.
(author)
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Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection
- 2015
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 47, s. 78-83
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Journal article (peer-reviewed)abstract
- Cervical artery dissection (CeAD), a mural hematoma in a carotid or vertebral artery, is a major cause of ischemic stroke in young adults although relatively uncommon in the general population (incidence of 2.6/100,000 per year)1. Minor cervical traumas, infection, migraine and hypertension are putative risk factors1–3, and inverse associations with obesity and hypercholesterolemia are described3,4. No confirmed genetic susceptibility factors have been identified using candidate gene approaches5. We performed genome-wide association studies (GWAS) in 1 1,393 CeAD cases and 1 14,416 controls. The rs9349379[G] allele (PHACTR1) was associated with lower CeAD risk (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.69–0.82; P = 4.46 × 1 10−10), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.91 1 × 1 10−3; combined P = 1 1.00 × 1 10−1111). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction6–9. Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions.
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| 29. |
- Salewski, M., et al.
(author)
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Diagnostic of fast-ion energy spectra and densities in magnetized plasmas
- 2019
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In: Journal of Instrumentation. - : Institute of Physics Publishing (IOPP). - 1748-0221. ; 14
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Journal article (peer-reviewed)abstract
- The measurement of the energy spectra and densities of alpha-particles and other fast ions are part of the ITER measurement requirements, highlighting the importance of energy-resolved energetic-particle measurements for the mission of ITER. However, it has been found in recent years that the velocity-space interrogation regions of the foreseen energetic-particle diagnostics do not allow these measurements directly. We will demonstrate this for gamma-ray spectroscopy (GRS), collective Thomson scattering (CTS), neutron emission spectroscopy and fast-ion D-alpha spectroscopy by invoking energy and momentum conservation in each case, highlighting analogies and differences between the different diagnostic velocity-space sensitivities. Nevertheless, energy spectra and densities can be inferred by velocity-space tomography which we demonstrate using measurements at JET and ASDEX Upgrade. The measured energy spectra agree well with corresponding simulations. At ITER, alpha-particle energy spectra and densities can be inferred for energies larger than 1.7 MeV by velocity-space tomography based on GRS and CTS. Further, assuming isotropy of the alpha-particles in velocity space, their energy spectra and densities can be inferred by 1D inversion of spectral single-detector measurements down to about 300 keV by CTS. The alpha-particle density can also be found by fitting a model to the CTS measurements assuming the alpha-particle distribution to be an isotropic slowing-down distribution.
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| 30. |
- Wilkinson, John L., et al.
(author)
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Pharmaceutical pollution of the world's rivers
- 2022
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:8
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Journal article (peer-reviewed)abstract
- Environmental exposure to active pharmaceutical ingredients (APIs) can have negative effects on the health of ecosystems and humans. While numerous studies have monitored APIs in rivers, these employ different analytical methods, measure different APIs, and have ignored many of the countries of the world. This makes it difficult to quantify the scale of the problem from a global perspective. Furthermore, comparison of the existing data, generated for different studies/regions/continents, is challenging due to the vast differences between the analytical methodologies employed. Here, we present a global-scale study of API pollution in 258 of the world's rivers, representing the environmental influence of 471.4 million people across 137 geographic regions. Samples were obtained from 1,052 locations in 104 countries (representing all continents and 36 countries not previously studied for API contamination) and analyzed for 61 APIs. Highest cumulative API concentrations were observed in sub-Saharan Africa, south Asia, and South America. The most contaminated sites were in low- to middle-income countries and were associated with areas with poor wastewater and waste management infrastructure and pharmaceutical manufacturing. The most frequently detected APIs were carbamazepine, metformin, and caffeine (a compound also arising from lifestyle use), which were detected at over half of the sites monitored. Concentrations of at least one API at 25.7% of the sampling sites were greater than concentrations considered safe for aquatic organisms, or which are of concern in terms of selection for antimicrobial resistance. Therefore, pharmaceutical pollution poses a global threat to environmental and human health, as well as to delivery of the United Nations Sustainable Development Goals.
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| 31. |
- Zamora, Juan Carlos, et al.
(author)
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Considerations and consequences of allowing DNA sequence data as types of fungal taxa
- 2018
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In: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
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Journal article (peer-reviewed)abstract
- Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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| 32. |
- Amare, Azmeraw T, et al.
(author)
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Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.
- 2023
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In: Molecular psychiatry. - 1476-5578. ; 28, s. 5251-5261
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Journal article (peer-reviewed)abstract
- Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental healthdisorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P=9.8×10-12, R2=1.9%) and continuous (P=6.4×10-9, R2=2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P=3.9×10-4, R2=0.9%), but not for the continuous outcome (P=0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.
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| 33. |
- Amare, Azmeraw T, et al.
(author)
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Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder: A Genome-Wide Association Study.
- 2018
-
In: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 65-74
-
Journal article (peer-reviewed)abstract
- Lithium is a first-line mood stabilizer for the treatment of bipolar affective disorder (BPAD). However, the efficacy of lithium varies widely, with a nonresponse rate of up to 30%. Biological response markers are lacking. Genetic factors are thought to mediate treatment response to lithium, and there is a previously reported genetic overlap between BPAD and schizophrenia (SCZ).To test whether a polygenic score for SCZ is associated with treatment response to lithium in BPAD and to explore the potential molecular underpinnings of this association.A total of 2586 patients with BPAD who had undergone lithium treatment were genotyped and assessed for long-term response to treatment between 2008 and 2013. Weighted SCZ polygenic scores were computed at different P value thresholds using summary statistics from an international multicenter genome-wide association study (GWAS) of 36989 individuals with SCZ and genotype data from patients with BPAD from the Consortium on Lithium Genetics. For functional exploration, a cross-trait meta-GWAS and pathway analysis was performed, combining GWAS summary statistics on SCZ and response to treatment with lithium. Data analysis was performed from September 2016 to February 2017.Treatment response to lithium was defined on both the categorical and continuous scales using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. The effect measures include odds ratios and the proportion of variance explained.Of the 2586 patients in the study (mean [SD] age, 47.2 [13.9] years), 1478 were women and 1108 were men. The polygenic score for SCZ was inversely associated with lithium treatment response in the categorical outcome, at a threshold P<5×10-2. Patients with BPAD who had a low polygenic load for SCZ responded better to lithium, with odds ratios for lithium response ranging from 3.46 (95% CI, 1.42-8.41) at the first decile to 2.03 (95% CI, 0.86-4.81) at the ninth decile, compared with the patients in the 10th decile of SCZ risk. In the cross-trait meta-GWAS, 15 genetic loci that may have overlapping effects on lithium treatment response and susceptibility to SCZ were identified. Functional pathway and network analysis of these loci point to the HLA antigen complex and inflammatory cytokines.This study provides evidence for a negative association between high genetic loading for SCZ and poor response to lithium in patients with BPAD. These results suggest the potential for translational research aimed at personalized prescribing of lithium.
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| 34. |
- Andreoni, Igor, et al.
(author)
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Target-of-opportunity Observations of Gravitational-wave Events with Vera C. Rubin Observatory
- 2022
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In: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 260:1
-
Journal article (peer-reviewed)abstract
- The discovery of the electromagnetic counterpart to the binary neutron star (NS) merger GW170817 has opened the era of gravitational-wave multimessenger astronomy. Rapid identification of the optical/infrared kilonova enabled a precise localization of the source, which paved the way to deep multiwavelength follow-up and its myriad of related science results. Fully exploiting this new territory of exploration requires the acquisition of electromagnetic data from samples of NS mergers and other gravitational-wave sources. After GW170817, the frontier is now to map the diversity of kilonova properties and provide more stringent constraints on the Hubble constant, and enable new tests of fundamental physics. The Vera C. Rubin Observatory's Legacy Survey of Space and Time can play a key role in this field in the 2020s, when an improved network of gravitational-wave detectors is expected to reach a sensitivity that will enable the discovery of a high rate of merger events involving NSs (∼tens per year) out to distances of several hundred megaparsecs. We design comprehensive target-of-opportunity observing strategies for follow-up of gravitational-wave triggers that will make the Rubin Observatory the premier instrument for discovery and early characterization of NS and other compact-object mergers, and yet unknown classes of gravitational-wave events.
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| 35. |
- Batistoni, P., et al.
(author)
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Benchmark experiments on neutron streaming through JET Torus Hall penetrations
- 2015
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In: Nuclear Fusion. - : IOP PUBLISHING LTD. - 0029-5515 .- 1741-4326. ; 55:5
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Journal article (peer-reviewed)abstract
- Neutronics experiments are performed at JET for validating in a real fusion environment the neutronics codes and nuclear data applied in ITER nuclear analyses. In particular, the neutron fluence through the penetrations of the JET torus hall is measured and compared with calculations to assess the capability of state-of-art numerical tools to correctly predict the radiation streaming in the ITER biological shield penetrations up to large distances from the neutron source, in large and complex geometries. Neutron streaming experiments started in 2012 when several hundreds of very sensitive thermo-luminescence detectors (TLDs), enriched to different levels in (LiF)-Li-6/(LiF)-Li-7, were used to measure the neutron and gamma dose separately. Lessons learnt from this first experiment led to significant improvements in the experimental arrangements to reduce the effects due to directional neutron source and self-shielding of TLDs. Here we report the results of measurements performed during the 2013-2014 JET campaign. Data from new positions, at further locations in the South West labyrinth and down to the Torus Hall basement through the air duct chimney, were obtained up to about a 40m distance from the plasma neutron source. In order to avoid interference between TLDs due to self-shielding effects, only TLDs containing natural Lithium and 99.97% Li-7 were used. All TLDs were located in the centre of large polyethylene (PE) moderators, with Li-nat and Li-7 crystals evenly arranged within two PE containers, one in horizontal and the other in vertical orientation, to investigate the shadowing effect in the directional neutron field. All TLDs were calibrated in the quantities of air kerma and neutron fluence. This improved experimental arrangement led to reduced statistical spread in the experimental data. The Monte Carlo N-Particle (MCNP) code was used to calculate the air kerma due to neutrons and the neutron fluence at detector positions, using a JET model validated up to the magnetic limbs. JET biological shield and penetrations, the PE moderators and TLDs were modelled in detail. Different tallying methods were used in the calculations, which are routinely used in ITER nuclear analyses: the mesh tally and the track length estimator with multiple steps calculations using the surface source write/read capability available in MCNP. In both cases, the calculated neutron fluence (C) was compared to the measured fluence (E) and hence C/E comparisons have been obtained and are discussed. These results provide a validation of neutronics numerical tools, codes and nuclear data, used for ITER design.
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| 36. |
- Carvalho, E. de, et al.
(author)
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EU FP7 INFSO-ICT-317669 METIS, D3.1 Positioning of multi-node/multi-antenna technologies
- 2013
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Reports (other academic/artistic)abstract
- This document describes the research activity in multi-node/multi-antenna technologies within METIS and positions it with respect to the state-of-the-art in the academic literature and in the standardization bodies. Based on the state-of-the-art and as well as on the METIS objectives,we set the research objectives and we group the different activities (or technology components) into research clusters with similar research objectives. The technologycomponents and the research objectives have been set to achieve an ambidextrous purpose. On one side we aim at providing the METIS system with those technological components that are a natural but non-trivial evolution of 4G. On the other side, we aim at seeking for disruptivetechnologies that could radically change 5G with respect to 4G. Moreover, we mapped the different technology components to METIS’ other activities and to the overall goals of theproject.
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| 37. |
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| 38. |
- Herrera-Rivero, Marisol, et al.
(author)
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Exploring the genetics of lithium response in bipolar disorders.
- 2023
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In: Research square.
-
Other publication (other academic/artistic)abstract
- Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N=2,064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II.We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism.Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.
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| 39. |
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| 40. |
- Kalman, Janos L, et al.
(author)
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Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study.
- 2019
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In: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 21:1, s. 68-75
-
Journal article (peer-reviewed)abstract
- Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early-onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD- and schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in BD patients.A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn-Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18years] vs adulthood [>18years]) or considered as a continuous measure. The associations between BD- and SCZ-PRSs and AAO were evaluated with regression models.BD- and SCZ-PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment.The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype.
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| 41. |
- Kim, Min Seo, et al.
(author)
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Global burden of peripheral artery disease and its risk factors, 1990-2019 : a systematic analysis for the Global Burden of Disease Study 2019
- 2023
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In: The Lancet Global Health. - : Elsevier. - 2214-109X. ; 11:10, s. E1553-E1565
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Journal article (peer-reviewed)abstract
- Background: Peripheral artery disease is a growing public health problem. We aimed to estimate the global disease burden of peripheral artery disease, its risk factors, and temporospatial trends to inform policy and public measures.Methods: Data on peripheral artery disease were modelled using the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2019 database. Prevalence, disability-adjusted life years (DALYs), and mortality estimates of peripheral artery disease were extracted from GBD 2019. Total DALYs and age-standardised DALY rate of peripheral artery disease attributed to modifiable risk factors were also assessed.Findings: In 2019, the number of people aged 40 years and older with peripheral artery disease was 113 million (95% uncertainty interval [UI] 99 center dot 2-128 center dot 4), with a global prevalence of 1 center dot 52% (95% UI 1 center dot 33-1 center dot 72), of which 42 center dot 6% was in countries with low to middle Socio-demographic Index (SDI). The global prevalence of peripheral artery disease was higher in older people, (14 center dot 91% [12 center dot 41-17 center dot 87] in those aged 80-84 years), and was generally higher in females than in males. Globally, the total number of DALYs attributable to modifiable risk factors in 2019 accounted for 69 center dot 4% (64 center dot 2-74 center dot 3) of total peripheral artery disease DALYs. The prevalence of peripheral artery disease was highest in countries with high SDI and lowest in countries with low SDI, whereas DALY and mortality rates showed U-shaped curves, with the highest burden in the high and low SDI quintiles.Interpretation: The total number of people with peripheral artery disease has increased globally from 1990 to 2019. Despite the lower prevalence of peripheral artery disease in males and low-income countries, these groups showed similar DALY rates to females and higher-income countries, highlighting disproportionate burden in these groups. Modifiable risk factors were responsible for around 70% of the global peripheral artery disease burden. Public measures could mitigate the burden of peripheral artery disease by modifying risk factors.
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| 42. |
- Salewski, M., et al.
(author)
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Bayesian Integrated Data Analysis of Fast-Ion Measurements by Velocity-Space Tomography
- 2018
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In: Fusion science and technology. - : TAYLOR & FRANCIS INC. - 1536-1055 .- 1943-7641. ; 74:1-2, s. 23-36
-
Journal article (peer-reviewed)abstract
- Bayesian integrated data analysis combines measurements from different diagnostics to jointly measure plasma parameters of interest such as temperatures, densities, and drift velocities. Integrated data analysis of fast-ion measurements has long been hampered by the complexity of the strongly non-Maxwellian fast-ion distribution functions. This has recently been overcome by velocity-space tomography. In this method two-dimensional images of the velocity distribution functions consisting of a few hundreds or thousands of pixels are reconstructed using the available fast-ion measurements. Here we present an overview and current status of this emerging technique at the ASDEX Upgrade tokamak and the JET toamak based on fast-ion D-alpha spectroscopy, collective Thomson scattering, gamma-ray and neutron emission spectrometry, and neutral particle analyzers. We discuss Tikhonov regularization within the Bayesian framework. The implementation for different types of diagnostics as well as the uncertainties are discussed, and we highlight the importance of integrated data analysis of all available detectors.
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| 43. |
- Vasilopoulou, T., et al.
(author)
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Neutron streaming along ducts and labyrinths at the JET biological shielding : Effect of concrete composition
- 2015
-
In: Radiation Physics and Chemistry. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0969-806X .- 1879-0895. ; 116, s. 359-364
-
Journal article (peer-reviewed)abstract
- Experiments and Monte Carlo simulations were performed at the Joint European Torus (JET) in order to validate the computational tools and methods applied for neutron streaming calculations through penetrations in the JET Hall biological shielding. In the present work the sensitivity of the simulations on the hydrogen and boron content in concrete shielding was investigated. MCNP code was used to simulate neutron streaming along the JET Hall personnel entrance labyrinth for deuterium-deuterium and deuterium-tritium plasma sources for different concrete wall compositions. Neutron fluence and ambient dose equivalent along the labyrinth were calculated. Simulation results for the "as built" JET concrete composition were compared against measurements performed using thermoluminescence detectors. This study contributes to the optimization of the radiation shielding of JET and, furthermore, provides information from JET experience that may assist in optimizing and validating the radiation shielding design methodology used in its successor fusion devices ITER and DEMO.
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| 44. |
- Weisen, H., et al.
(author)
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The 'neutron deficit' in the JET tokamak
- 2017
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In: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 57:7
-
Journal article (peer-reviewed)abstract
- The measured D-D neutron rate of neutral beam heated JET baseline and hybrid H-modes in deuterium is found to be between approximately 50% and 100% of the neutron rate expected from the TRANSP code, depending on the plasma parameters. A number of candidate explanations for the shortfall, such as fuel dilution, errors in beam penetration and effectively available beam power have been excluded. As the neutron rate in JET is dominated by beamplasma interactions, the ` neutron deficit' may be caused by a yet unidentified form of fast particle redistribution. Modelling, which assumes fast particle transport to be responsible for the deficit, indicates that such redistribution would have to happen at time scales faster than both the slowing down time and the energy confinement time. Sawteeth and edge localised modes are found to make no significant contribution to the deficit. There is also no obvious correlation with magnetohydrodynamic activity measured using magnetic probes at the tokamak vessel walls. Modelling of fast particle orbits in the 3D fields of neoclassical tearing modes shows that realistically sized islands can only contribute a few percent to the deficit. In view of these results it appears unlikely that the neutron deficit results from a single physical process in the plasma.
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| 45. |
- Aamer, Aysha, et al.
(author)
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A precursor plateau and pre-maximum [O ii] emission in the superluminous SN2019szu : a pulsational pair-instability candidate
- 2023
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In: Monthly notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 527:4, s. 11970-11995
-
Journal article (peer-reviewed)abstract
- We present a detailed study on SN2019szu, a Type I superluminous supernova at z = 0.213 that displayed unique photometric and spectroscopic properties. Pan-STARRS and ZTF forced photometry show a pre-explosion plateau lasting ∼40 d. Unlike other SLSNe that show decreasing photospheric temperatures with time, the optical colours show an apparent temperature increase from ∼15 000 to ∼20 000 K over the first 70 d, likely caused by an additional pseudo-continuum in the spectrum. Remarkably, the spectrum displays a forbidden emission line (likely attributed to λλ7320,7330) visible 16 d before maximum light, inconsistent with an apparently compact photosphere. This identification is further strengthened by the appearances of [O III] λλ4959, 5007, and [O III] λ4363 seen in the spectrum. Comparing with nebular spectral models, we find that the oxygen line fluxes and ratios can be reproduced with ∼0.25 M⊙ of oxygen-rich material with a density of ∼10−15 g cm−3. The low density suggests a circumstellar origin, but the early onset of the emission lines requires that this material was ejected within the final months before the terminal explosion, consistent with the timing of the precursor plateau. Interaction with denser material closer to the explosion likely produced the pseudo-continuum bluewards of ∼5500 Å. We suggest that this event is one of the best candidates to date for a pulsational pair-instability ejection, with early pulses providing the low density material needed for the formation of the forbidden emission line, and collisions between the final shells of ejected material producing the pre-explosion plateau.
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| 46. |
- Aguzzi, Jacopo, et al.
(author)
-
Developing technological synergies between deep-sea and space research
- 2022
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In: Elementa. - 2325-1026. ; 10
-
Journal article (peer-reviewed)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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| 47. |
- Artiglia, Luca, et al.
(author)
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A surface-stabilized ozonide triggers bromide oxidation at the aqueous solution-vapour interface
- 2017
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Journal article (peer-reviewed)abstract
- Oxidation of bromide in aqueous environments initiates the formation of molecular halogen compounds, which is important for the global tropospheric ozone budget. In the aqueous bulk, oxidation of bromide by ozone involves a [Br center dot OOO-] complex as intermediate. Here we report liquid jet X-ray photoelectron spectroscopy measurements that provide direct experimental evidence for the ozonide and establish its propensity for the solution-vapour interface. Theoretical calculations support these findings, showing that water stabilizes the ozonide and lowers the energy of the transition state at neutral pH. Kinetic experiments confirm the dominance of the heterogeneous oxidation route established by this precursor at low, atmospherically relevant ozone concentrations. Taken together, our results provide a strong case of different reaction kinetics and mechanisms of reactions occurring at the aqueous phase-vapour interface compared with the bulk aqueous phase.
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| 48. |
- Backes, Claudia, et al.
(author)
-
Production and processing of graphene and related materials
- 2020
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In: 2D Materials. - : IOP Publishing. - 2053-1583. ; 7:2
-
Journal article (peer-reviewed)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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| 49. |
- Baiocchi, B., et al.
(author)
-
Transport analysis and modelling of the evolution of hollow density profiles plasmas in JET and implication for ITER
- 2015
-
In: Nuclear Fusion. - : IOP PUBLISHING LTD. - 0029-5515 .- 1741-4326. ; 55:12
-
Journal article (peer-reviewed)abstract
- The density evolution during the transient phase just after the L-H transition is investigated using theoretical transport models. Cases characterized by core densities which evolve in longer timescales than the edge densities, leading to hollow density profiles (R/L-n = -R del n/n < 0) are modelled. This density evolution is particularly interesting because it has been shown to be beneficial in the view of the access to burning plasma conditions in ITER (Loarte et al 2013 Nucl. Fusion 53 083031). Self-consistent simulations of the JET discharge 79676 of the density-only, and of the density and the temperatures are carried out using a quasilinear gyrokinetic code, QuaLiKiz (Bourdelle et al 2007 Phys. Plasmas 14 112501), coupled with a transport code CRONOS (Artaud et al 2010 Nucl. Fusion 50 043001). The slow evolution of the hollow density, associated with the self-consistently calculated hollow NBI particle deposition, is well reproduced in the plasma core. Indeed, QuaLiKiz is shown to reproduce nonlinear gyrokinetic heat and particle fluxes well for both positive and negative R/L-n. That gives a theoretical and general basis for the persistence of the hollowness, laying the groundwork for the extrapolation to ITER.
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| 50. |
- Baiocchi, B., et al.
(author)
-
Turbulent transport analysis of JET H-mode and hybrid plasmas using QuaLiKiz and Trapped Gyro Landau Fluid
- 2015
-
In: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 0741-3335 .- 1361-6587. ; 57:3
-
Journal article (peer-reviewed)abstract
- The physical transport processes at the basis of JET typical inductive H-mode scenarios and advanced hybrid regimes, with improved thermal confinement, are analyzed by means of some of the newest and more sophisticated quasi-linear transport models: trapped gyro Landau fluid (TGLF) and QuaLiKiz. The temporal evolution of JET pulses is modelled by CRONOS where the turbulent transport is modelled by either QuaLiKiz or TGLF. Both are first principle models with a more comprehensive physics than the models previously developed and therefore allow the analysis of the physics at the basis of the investigated scenarios. For H-modes, ion temperature gradient (ITG) modes are found to be dominant and the transport models are able to properly reproduce temperature profiles in self-consistent simulations. However, for hybrid regimes, in addition to ITG trapped electron modes (TEM) are also found to be important and different physical mechanisms for turbulence reduction play a decisive role. Whereas E x B flow shear and plasma geometry have a limited impact on turbulence, the presence of a large population of fast ions, quite important in low density regimes, can stabilize core turbulence mainly when the electromagnetic effects are taken into account. The TGLF transport model properly captures these mechanisms and correctly reproduces temperatures.
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