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- Abdalla, H., et al.
(author)
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Sensitivity of the Cherenkov Telescope Array for probing cosmology and fundamental physics with gamma-ray propagation
- 2021
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In: Journal of Cosmology and Astroparticle Physics. - : Institute of Physics Publishing (IOPP). - 1475-7516. ; :2
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Journal article (peer-reviewed)abstract
- The Cherenkov Telescope Array (CTA), the new-generation ground-based observatory for gamma-ray astronomy, provides unique capabilities to address significant open questions in astrophysics, cosmology, and fundamental physics. We study some of the salient areas of gamma-ray cosmology that can be explored as part of the Key Science Projects of CTA, through simulated observations of active galactic nuclei (AGN) and of their relativistic jets. Observations of AGN with CTA will enable a measurement of gamma-ray absorption on the extragalactic background light with a statistical uncertainty below 15% up to a redshift z = 2 and to constrain or detect gamma-ray halos up to intergalactic-magnetic-field strengths of at least 0.3 pG. Extragalactic observations with CTA also show promising potential to probe physics beyond the Standard Model. The best limits on Lorentz invariance violation from gamma-ray astronomy will be improved by a factor of at least two to three. CTA will also probe the parameter space in which axion-like particles could constitute a significant fraction, if not all, of dark matter. We conclude on the synergies between CTA and other upcoming facilities that will foster the growth of gamma-ray cosmology.
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- Menkveld, Albert J., et al.
(author)
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Nonstandard Errors
- 2024
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In: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
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Journal article (peer-reviewed)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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- Tschiderer, L., et al.
(author)
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Association of Intima-Media Thickness Measured at the Common Carotid Artery With Incident Carotid Plaque: Individual Participant Data Meta-Analysis of 20 Prospective Studies
- 2023
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In: Journal of the American Heart Association (JAHA). - 2047-9980. ; 12:12
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Journal article (peer-reviewed)abstract
- BackgroundThe association between common carotid artery intima-media thickness (CCA-IMT) and incident carotid plaque has not been characterized fully. We therefore aimed to precisely quantify the relationship between CCA-IMT and carotid plaque development. Methods and ResultsWe undertook an individual participant data meta-analysis of 20 prospective studies from the Proof-ATHERO (Prospective Studies of Atherosclerosis) consortium that recorded baseline CCA-IMT and incident carotid plaque involving 21 494 individuals without a history of cardiovascular disease and without preexisting carotid plaque at baseline. Mean baseline age was 56 years (SD, 9 years), 55% were women, and mean baseline CCA-IMT was 0.71 mm (SD, 0.17 mm). Over a median follow-up of 5.9 years (5th-95th percentile, 1.9-19.0 years), 8278 individuals developed first-ever carotid plaque. We combined study-specific odds ratios (ORs) for incident carotid plaque using random-effects meta-analysis. Baseline CCA-IMT was approximately log-linearly associated with the odds of developing carotid plaque. The age-, sex-, and trial arm-adjusted OR for carotid plaque per SD higher baseline CCA-IMT was 1.40 (95% CI, 1.31-1.50; I-2=63.9%). The corresponding OR that was further adjusted for ethnicity, smoking, diabetes, body mass index, systolic blood pressure, low- and high-density lipoprotein cholesterol, and lipid-lowering and antihypertensive medication was 1.34 (95% CI, 1.24-1.45; I-2=59.4%; 14 studies; 16 297 participants; 6381 incident plaques). We observed no significant effect modification across clinically relevant subgroups. Sensitivity analysis restricted to studies defining plaque as focal thickening yielded a comparable OR (1.38 [95% CI, 1.29-1.47]; I-2=57.1%; 14 studies; 17 352 participants; 6991 incident plaques). ConclusionsOur large-scale individual participant data meta-analysis demonstrated that CCA-IMT is associated with the long-term risk of developing first-ever carotid plaque, independent of traditional cardiovascular risk factors.
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4. |
- Grasselli, Giacomo, et al.
(author)
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ESICM guidelines on acute respiratory distress syndrome : definition, phenotyping and respiratory support strategies
- 2023
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In: Intensive Care Medicine. - : Springer Nature. - 0342-4642 .- 1432-1238. ; 49, s. 727-759
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Journal article (peer-reviewed)abstract
- The aim of these guidelines is to update the 2017 clinical practice guideline (CPG) of the European Society of Intensive Care Medicine (ESICM). The scope of this CPG is limited to adult patients and to non-pharmacological respiratory support strategies across different aspects of acute respiratory distress syndrome (ARDS), including ARDS due to coronavirus disease 2019 (COVID-19). These guidelines were formulated by an international panel of clinical experts, one methodologist and patients' representatives on behalf of the ESICM. The review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence and grade recommendations and the quality of reporting of each study based on the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network guidelines. The CPG addressed 21 questions and formulates 21 recommendations on the following domains: (1) definition; (2) phenotyping, and respiratory support strategies including (3) high-flow nasal cannula oxygen (HFNO); (4) non-invasive ventilation (NIV); (5) tidal volume setting; (6) positive end-expiratory pressure (PEEP) and recruitment maneuvers (RM); (7) prone positioning; (8) neuromuscular blockade, and (9) extracorporeal life support (ECLS). In addition, the CPG includes expert opinion on clinical practice and identifies the areas of future research.
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5. |
- Tur, C, et al.
(author)
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The risk of infections for multiple sclerosis and neuromyelitis optica spectrum disorder disease-modifying treatments: Eighth European Committee for Treatment and Research in Multiple Sclerosis Focused Workshop Review. April 2021
- 2022
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In: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 28:9, s. 1424-1456
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Journal article (peer-reviewed)abstract
- Over the recent years, the treatment of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) has evolved very rapidly and a large number of disease-modifying treatments (DMTs) are now available. However, most DMTs are associated with adverse events, the most frequent of which being infections. Consideration of all DMT-associated risks facilitates development of risk mitigation strategies. An international focused workshop with expert-led discussions was sponsored by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and was held in April 2021 to review our current knowledge about the risk of infections associated with the use of DMTs for people with MS and NMOSD and corresponding risk mitigation strategies. The workshop addressed DMT-associated infections in specific populations, such as children and pregnant women with MS, or people with MS who have other comorbidities or live in regions with an exceptionally high infection burden. Finally, we reviewed the topic of DMT-associated infectious risks in the context of the current SARS-CoV-2 pandemic. Herein, we summarize available evidence and identify gaps in knowledge which justify further research.
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6. |
- Bonomi, A, et al.
(author)
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Analysis of the genetic variants associated with circulating levels of sgp130. Results from the IMPROVE study
- 2020
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In: Genes and immunity. - : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 21:2, s. 100-108
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Journal article (peer-reviewed)abstract
- The genes regulating circulating levels of soluble gp130 (sgp130), the antagonist of the inflammatory response in atherosclerosis driven by interleukin 6, are largely unknown. Aims of the present study were to identify genetic loci associated with circulating sgp130 and to explore the potential association between variants associated with sgp130 and markers of subclinical atherosclerosis. The study is based on IMPROVE (n = 3703), a cardiovascular multicentre study designed to investigate the determinants of carotid intima media thickness, a measure of subclinical atherosclerosis. Genomic DNA was genotyped by the CardioMetaboChip and ImmunoChip. About 360,842 SNPs were tested for association with log-transformed sgp130, using linear regression adjusted for age, gender, and population stratification using PLINK v1.07. A p value of 1 × 10−5 was chosen as threshold for significance value. In an exploratory analysis, SNPs associated with sgp130 were tested for association with c-IMT measures. We identified two SNPs significantly associated with sgp130 levels and 24 showing suggestive association with sgp130 levels. One SNP (rs17688225) on chromosome 14 was positively associated with sgp130 serum levels (β = 0.03 SE = 0.007, p = 4.77 × 10−5) and inversely associated with c-IMT (c-IMTmean–maxβ = −0.001 SE = 0.005, p = 0.0342). Our data indicate that multiple loci regulate sgp130 levels and suggest a possible common pathway between sgp130 and c-IMT measures.
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7. |
- Colombo, GI, et al.
(author)
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The Association between HDL-C and Subclinical Atherosclerosis Depends on CETP Plasma Concentration: Insights from the IMPROVE Study
- 2021
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In: Biomedicines. - : MDPI AG. - 2227-9059. ; 9:3
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Journal article (peer-reviewed)abstract
- The impact of cholesteryl ester transfer protein (CETP) on atherosclerosis is highly debated. This study aimed to investigate the associations between plasma CETP or CETP genotypes and carotid intima-media thickness (cIMT) and the influence of high-density lipoprotein cholesterol (HDL-C) on these associations. Plasma CETP and HDL-C concentrations were measured in 552 subjects free of any pharmacological treatment from the IMPROVE cohort, which includes 3711 European subjects at high cardiovascular risk. CETP single-nucleotide polymorphisms (SNPs) and cIMT measures (cIMTmax; cIMTmean–max of bifurcations, common and internal carotids; plaque-free common carotid [PF CC]-IMTmean) were available for the full cohort. In drug-free subjects, plasma CETP correlated with HDL-C levels (r = 0.19, p < 0.0001), but not with cIMT variables. When stratified according to HDL-C quartiles, CETP positively correlated with cIMTmax and cIMTmean–max, but not with PF CC-IMTmean, in the top HDL-C quartile only. Positive associations between the CETP concentration and cIMTmax or cIMTmean–max were found in the top HDL-C quartile, whereas HDL-C levels were negatively correlated with cIMTmax and cIMTmean–max when the CETP concentration was below the median (HDL-C × CETP interaction, p = 0.001 and p = 0.003 for cIMTmax and cIMTmean–max, respectively). In the full cohort, three CETP SNPs (rs34760410, rs12920974, rs12708968) were positively associated with cIMTmax. rs12444708 exhibited a significant interaction with HDL-C levels in the prediction of cIMTmax. In conclusion, a significant interplay was found between plasma CETP and/or CETP genotype and HDL-C in the prediction of carotid plaque thickness, as indexed by cIMTmax. This suggests that the association of HDL-C with carotid atherosclerosis is CETP-dependent.
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- Amato, S, et al.
(author)
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Comparing trauma mortality of injured patients in India and the USA: a risk-adjusted analysis
- 2021
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In: Trauma surgery & acute care open. - : BMJ. - 2397-5776. ; 6:1, s. e000719-
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Journal article (peer-reviewed)abstract
- Comparisons of risk-adjusted trauma mortality between high-income countries and low and middle-income countries (LMICs) can be used to identify specific patient populations and injury patterns for targeted interventions. Due to a paucity of granular patient and injury data from LMICs, there is a lack of such comparisons. This study aims to identify independent predictors of trauma mortality and significant differences between India and the USA.MethodsA retrospective cohort study of two trauma databases was conducted. Demographic, injury, physiologic, anatomic and outcome data were analyzed from India’s Towards Improved Trauma Care Outcomes project database and the US National Trauma Data Bank from 2013 to 2015. Multivariate logistic regression analyses were performed to determine significant independent predictors of mortality.Results687 407 adult trauma patients were included (India 11 796; USA 675 611). Patients from India were significantly younger with greater male preponderance, a higher proportion presented with physiologic abnormalities and suffered higher mortality rates (23.2% vs. 2.8%). When controlling for age, sex, physiologic abnormalities, and injury severity, sustaining an injury in India was the strongest predictor of mortality (OR 13.85, 95% CI 13.05 to 14.69). On subgroup analyses, the greatest mortality difference was seen in patients with lower Injury Severity Scores.ConclusionAfter adjusting for demographic, physiologic abnormalities, and injury severity, trauma-related mortality was found to be significantly higher in India. When compared with trauma patients in the USA, the odds of mortality are most notably different among patients with lower Injury Severity Scores. While troubling, this suggests that relatively simple, low-cost interventions focused on standard timely trauma care, early imaging, and protocolized treatment pathways could result in substantial improvements for injury mortality in India, and potentially other LMICs.Level of evidenceLevel 3, retrospective cohort study.
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