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- Amati, L., et al.
(författare)
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The THESEUS space mission concept : science case, design and expected performances
- 2018
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Ingår i: Advances in Space Research. - : ELSEVIER SCI LTD. - 0273-1177 .- 1879-1948. ; 62:1, s. 191-244
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Tidskriftsartikel (refereegranskat)abstract
- THESEUS is a space mission concept aimed at exploiting Gamma-Ray Bursts for investigating the early Universe and at providing a substantial advancement of multi-messenger and time-domain astrophysics. These goals will be achieved through a unique combination of instruments allowing GRB and X-ray transient detection over a broad field of view (more than 1 sr) with 0.5-1 arcmin localization, an energy band extending from several MeV down to 0.3 keV and high sensitivity to transient sources in the soft X-ray domain, as well as on-board prompt (few minutes) follow-up with a 0.7 m class IR telescope with both imaging and spectroscopic capabilities. THESEUS will be perfectly suited for addressing the main open issues in cosmology such as, e.g., star formation rate and metallicity evolution of the inter-stellar and intra-galactic medium up to redshift similar to 10, signatures of Pop III stars, sources and physics of re-ionization, and the faint end of the galaxy luminosity function. In addition, it will provide unprecedented capability to monitor the X-ray variable sky, thus detecting, localizing, and identifying the electromagnetic counterparts to sources of gravitational radiation, which may be routinely detected in the late '20s/early '30s by next generation facilities like aLIGO/ aVirgo, eLISA, KAGRA, and Einstein Telescope. THESEUS will also provide powerful synergies with the next generation of multi-wavelength observatories (e.g., LSST, ELT, SKA, CTA, ATHENA).
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- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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- Dalmasso, MC, et al.
(författare)
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Transethnic meta-analysis of rare coding variants in PLCG2, ABI3, and TREM2 supports their general contribution to Alzheimer's disease
- 2019
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 9:1, s. 55-
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Tidskriftsartikel (refereegranskat)abstract
- Rare coding variants in TREM2, PLCG2, and ABI3 were recently associated with the susceptibility to Alzheimer’s disease (AD) in Caucasians. Frequencies and AD-associated effects of variants differ across ethnicities. To start filling the gap on AD genetics in South America and assess the impact of these variants across ethnicity, we studied these variants in Argentinian population in association with ancestry. TREM2 (rs143332484 and rs75932628), PLCG2 (rs72824905), and ABI3 (rs616338) were genotyped in 419 AD cases and 486 controls. Meta-analysis with European population was performed. Ancestry was estimated from genome-wide genotyping results. All variants show similar frequencies and odds ratios to those previously reported. Their association with AD reach statistical significance by meta-analysis. Although the Argentinian population is an admixture, variant carriers presented mainly Caucasian ancestry. Rare coding variants in TREM2, PLCG2, and ABI3 also modulate susceptibility to AD in populations from Argentina, and they may have a European heritage.
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- Farmakis, D., et al.
(författare)
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Levosimendan beyond inotropy and acute heart failure: Evidence of pleiotropic effects on the heart and other organs: An expert panel position paper
- 2016
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 222, s. 303-312
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Tidskriftsartikel (refereegranskat)abstract
- Levosimendan is a positive inotrope with vasodilating properties (inodilator) indicated for decompensated heart failure (HF) patients with low cardiac output. Accumulated evidence supports several pleiotropic effects of levosimendan beyond inotropy, the heart and decompensated HF. Those effects are not readily explained by cardiac function enhancement and seem to be related to additional properties of the drug such as anti-inflammatory, anti-oxidative and anti-apoptotic ones. Mechanistic and proof-of-concept studies are still required to clarify the underlying mechanisms involved, while properly designed clinical trials are warranted to translate preclinical or early-phase clinical data into more robust clinical evidence. The present position paper, derived by a panel of 35 experts in the field of cardiology, cardiac anesthesiology, intensive care medicine, cardiac physiology, and cardiovascular pharmacology from 22 European countries, compiles the existing evidence on the pleiotropic effects of levosimendan, identifies potential novel areas of clinical application and defines the corresponding gaps in evidence and the required research efforts to address those gaps. © 2016 The Authors
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- Lange, Dale J., et al.
(författare)
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Pyrimethamine Significantly Lowers Cerebrospinal Fluid Cu/Zn Superoxide Dismutase in Amyotrophic Lateral Sclerosis Patients with SOD1 Mutations
- 2017
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Ingår i: Annals of Neurology. - : John Wiley & Sons. - 0364-5134 .- 1531-8249. ; 81:6, s. 837-848
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Cu/Zn superoxide dismutase (SOD1) reduction prolongs survival in SOD1-transgenic animal models. Pyrimethamine produces dose-dependent SOD1 reduction in cell culture systems. A previous phase 1 trial showed pyrimethamine lowers SOD1 levels in leukocytes in patients with SOD1 mutations. This study investigated whether pyrimethamine lowered SOD1 levels in the cerebrospinal fluid (CSF) in patients carrying SOD1 mutations linked to familial amyotrophic lateral sclerosis (fALS/SOD1). Methods: A multicenter (5 sites), open-label, 9-month-duration, dose-ranging study was undertaken to determine the safety and efficacy of pyrimethamine to lower SOD1 levels in the CSF in fALS/SOD1. All participants underwent 3 lumbar punctures, blood draw, clinical assessment of strength, motor function, quality of life, and adverse effect assessments. SOD1 levels were measured in erythrocytes and CSF. Pyrimethamine was measured in plasma and CSF. Appel ALS score, ALS Functional Rating Scale-Revised, and McGill Quality of Life Single-Item Scale were measured at screening, visit 6, and visit 9. Results: We enrolled 32 patients; 24 completed 6 visits (18 weeks), and 21 completed all study visits. A linear mixed effects model showed a significant reduction in CSF SOD1 at visit 6 (p<0.001) with a mean reduction of 13.5% (95% confidence interval [CI] 58.4-18.5) and at visit 9 (p<0.001) with a mean reduction of 10.5% (95% CI55.2-15.8). Interpretation: Pyrimethamine is safe and well tolerated in ALS. Pyrimethamine is capable of producing a significant reduction in total CSF SOD1 protein content in patients with ALS caused by different SOD1 mutations. Further long-term studies are warranted to assess clinical efficacy.
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| 8. |
- Morelli, F., et al.
(författare)
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Optimal Experiment Design for the Identification of One Module in the Interconnection of Locally Controlled Systems
- 2019
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Ingår i: 2019 18TH EUROPEAN CONTROL CONFERENCE (ECC). - : IEEE. ; , s. 363-368
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Konferensbidrag (refereegranskat)abstract
- In this paper, we consider the problem of designing the least costly experiment that leads to a sufficiently accurate estimate of one module in a network of locally controlled systems. A module in such a network can be identified by exciting the corresponding local closed loop system. Such an excitation signal will not only perturb the input/output of the to-be-identified module, but also other modules due to the interconnection. Consequently, the cost of the identification can be expressed as the sum of the influence of the excitation signal on the inputs and outputs of all locally controlled systems. We develop a methodology to design the spectrum of the excitation signal in such a way that this cost is minimized while guaranteeing a certain accuracy for the identified model. We also propose an alternative identification configuration which can further reduce the propagation of the excitation signal to other modules and we make steps to robustify this optimal experiment design problem with respect to the cost of the identification.
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| 10. |
- van den Nieuwboer, M., et al.
(författare)
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Safety of probiotics and synbiotics in children under 18 years of age
- 2015
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Ingår i: Beneficial Microbes. - : Wageningen Academic Publishers. - 1876-2883 .- 1876-2891. ; 6:5, s. 615-630
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to systematically evaluate safety of probiotics and synbiotics in children ageing 0-18 years. This study is the third and final part in a safety trilogy and an update is provided using the most recent available clinical data (2008-2013) by means of the Common Terminology Clinical Adverse Events (CTCAE version 4.0) classification. Safety aspects are represented and related to number of participants per probiotic strain/culture, study duration, dosage, clinical condition and selected afflictions. Analysis of 74 clinical studies indicated that probiotic and/or synbiotic administration in children is safe with regard to the specific evaluated strains, dosages and duration. The population of children include healthy, immune compromised and obese subjects, as well as subjects with intestinal disorders, infections and inflammatory disorders. This study revealed no major safety concerns, as the adverse events (AEs) were unrelated, or not suspected to be related, to the probiotic or synbiotic product. In general the study products were well tolerated. Overall, AEs occurred more frequent in the control arm compared to children receiving probiotics and/or synbiotics. Furthermore, the results indicate inadequate reporting and classification of AEs in the majority of the studies. In addition, generalizability of conclusions are greatly limited by the inconsistent, imprecise and potentially incomplete reporting as well as the variation in probiotic strains, dosages, administration regimes, study populations and reported outcomes.
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