| 1. |
- Solmi, Marco, et al.
(författare)
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Validation of the Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) questionnaire for adults
- 2023
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Ingår i: Journal of Affective Disorders. - : ELSEVIER. - 0165-0327 .- 1573-2517. ; 326, s. 249-261
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Collaborative Outcome study on Health and Functioning during Infection Times (COH-FIT; www.coh-fit.com) is an anonymous and global online survey measuring health and functioning during the COVID-19 pandemic. The aim of this study was to test concurrently the validity of COH-FIT items and the in-ternal validity of the co-primary outcome, a composite psychopathology "P-score". Methods: The COH-FIT survey has been translated into 30 languages (two blind forward-translations, consensus, one independent English back-translation, final harmonization). To measure mental health, 1-4 items ("COH-FIT items") were extracted from validated questionnaires (e.g. Patient Health Questionnaire 9). COH-FIT items measured anxiety, depressive, post-traumatic, obsessive-compulsive, bipolar and psychotic symptoms, as well as stress, sleep and concentration. COH-FIT Items which correlated r >= 0.5 with validated companion question-naires, were initially retained. A P-score factor structure was then identified from these items using exploratory factor analysis (EFA) and confirmatory factor analyses (CFA) on data split into training and validation sets. Consistency of results across languages, gender and age was assessed. Results: From >150,000 adult responses by May 6th, 2022, a subset of 22,456 completed both COH-FIT items and validated questionnaires. Concurrent validity was consistently demonstrated across different languages for COH-FIT items. CFA confirmed EFA results of five first-order factors (anxiety, depression, post-traumatic, psychotic, psychophysiologic symptoms) and revealed a single second-order factor P-score, with high internal reliability (omega = 0.95). Factor structure was consistent across age and sex. Conclusions: COH-FIT is a valid instrument to globally measure mental health during infection times. The P-score is a valid measure of multidimensional mental health.
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| 2. |
- Hernández‑Morcillo, Monica, et al.
(författare)
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Scanning the solutions for the sustainable supply of forest ecosystem services in Europe
- 2022
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Ingår i: Sustainability Science. - : Springer Science and Business Media LLC. - 1862-4057 .- 1862-4065. ; 17:5, s. 2013-2029
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Tidskriftsartikel (refereegranskat)abstract
- Forests are key components of European multifunctional landscapes and supply numerous forest ecosystem services (FES) fundamental to human well-being. The sustainable provision of FES has the potential to provide responses to major societal challenges, such as climate change, biodiversity loss, or rural development. To identify suitable strategies for the future sustenance of FES, we performed a solution scanning exercise with a group of transdisciplinary forest and FES experts from diferent European regions. We identifed and prioritized ffteen major challenges hindering the balanced provision of multiple FES and identifed a series of potential solutions to tackle each of them. The most prominent challenges referred to the increased frequency and impacts of extreme weather events and the normative mindset regarding forest management. The respective solutions pointed to the promotion of forest resilience via climate-smart forestry and mainstreaming FES-orientedmanagement through a threefold strategy focusing on education, awareness raising, and networking. In a subsequent survey,most solutions were assessed as highly efective, transferable, monitorable, and with potential for being economically efcient. The implementation of the solutions could have synergistic efects when applying the notion of leverage points. Sevenemerging pathways towards the sustainable supply of FES have been identifed. These pathways build on each other and areorganized based on their potential for transformation: (1) shifting forest management paradigms towards pluralistic ecosystem valuation; (2) using integrated landscape approaches; (3) increasing forest resilience; (4) coordinating actions betweenforest-related actors; (5) increasing participation in forest planning and management; (6) continuous, open, and transparentknowledge integration; and (7) using incentive-based instruments to support regulating and cultural FES. These pathwayscan contribute to the implementation of the new EU Forestry Strategy to support the balanced supply of multiple FES.
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| 3. |
- Li, Ping, et al.
(författare)
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PcoB is a defense outer membrane protein that facilitates cellular uptake of copper
- 2022
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Ingår i: Protein Science. - : Wiley. - 0961-8368 .- 1469-896X. ; 31:7
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Tidskriftsartikel (refereegranskat)abstract
- Copper (Cu) is one of the most abundant trace metals in all organisms, involved in a plethora of cellular processes. Yet elevated concentrations of the element are harmful, and interestingly prokaryotes are more sensitive for environmental Cu stress than humans. Various transport systems are present to maintain intracellular Cu homeostasis, including the prokaryotic plasmid-encoded multiprotein pco operon, which is generally assigned as a defense mechanism against elevated Cu concentrations. Here we structurally and functionally characterize the outer membrane component of the Pco system, PcoB, recovering a 2.0 Å structure, revealing a classical β-barrel architecture. Unexpectedly, we identify a large opening on the extracellular side, linked to a considerably electronegative funnel that becomes narrower towards the periplasm, defining an ion-conducting pathway as also supported by metal binding quantification via inductively coupled plasma mass spectrometry and molecular dynamics (MD) simulations. However, the structure is partially obstructed towards the periplasmic side, and yet flux is permitted in the presence of a Cu gradient as shown by functional characterization in vitro. Complementary in vivo experiments demonstrate that isolated PcoB confers increased sensitivity towards Cu. Aggregated, our findings indicate that PcoB serves to permit Cu import. Thus, it is possible the Pco system physiologically accumulates Cu in the periplasm as a part of an unorthodox defense mechanism against metal stress. These results point to a previously unrecognized principle of maintaining Cu homeostasis and may as such also assist in the understanding and in efforts towards combatting bacterial infections of Pco-harboring pathogens.
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| 6. |
- Walsh, Roddy, et al.
(författare)
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Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls
- 2021
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Ingår i: Genetics in Medicine. - : Nature Publishing Group. - 1098-3600 .- 1530-0366. ; 23:1, s. 47-58
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate.Methods: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants.Results: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 x 10(-18)) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 x 10(-13)). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency.Conclusion: Large case-control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing.
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| 7. |
- Schroder, Jakob, et al.
(författare)
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Prognosis And Reclassification By YKL-40 In Stable Coronary Artery Disease
- 2020
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Ingår i: Journal of the American Heart Association. - 2047-9980 .- 2047-9980. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe inflammatory biomarker YKL‐40 has previously been studied as a potential risk marker in cardiovascular disease. We aimed to assess the prognostic reclassification potential of serum YKL‐40 in patients with stable coronary artery disease.Methods and ResultsThe main study population was the placebo group of the CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) trial. The primary outcome was a composite of acute myocardial infarction, unstable angina pectoris, cerebrovascular disease, and all‐cause mortality. We used Cox proportional hazards regression models adjusted for C‐reactive protein level and baseline cardiovascular risk factors. Improvement in prediction by adding serum YKL‐40 to the risk factors was calculated using the Cox‐Breslow method and c‐statistic. A total of 2200 patients were randomized to placebo, with a follow‐up duration of 10 years. YKL‐40 was associated with an increased risk of the composite outcome (hazard ratio per unit increase in (YKL‐40) 1.13, 95% CI 1.03–1.24, P=0.013) and all‐cause mortality (hazard ratio 1.32, 95% CI 1.17–1.49, P<0.0001). Considering whether a composite‐outcome event was more likely to have, or not have, occurred to date, we found 68.4% of such predictions to be correct when based on the standard predictors, and 68.5% when serum YKL‐40 was added as a predictor. Equivalent results were obtained with c‐statistics.ConclusionsHigher serum YKL‐40 was independently associated with an increased risk of adverse cardiovascular outcomes and mortality. Addition of YKL‐40 did not improve risk prediction in patients with stable coronary artery disease.
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| 8. |
- Reifarth, R., et al.
(författare)
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Nuclear astrophysics with radioactive ions at FAIR
- 2016
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Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 665:1
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Konferensbidrag (refereegranskat)abstract
- The nucleosynthesis of elements beyond iron is dominated by neutron captures in the s and r processes. However, 32 stable, proton-rich isotopes cannot be formed during those processes, because they are shielded from the s-process flow and r-process beta-decay chains. These nuclei are attributed to the p and rp process. For all those processes, current research in nuclear astrophysics addresses the need for more precise reaction data involving radioactive isotopes. Depending on the particular reaction, direct or inverse kinematics, forward or time-reversed direction are investigated to determine or at least to constrain the desired reaction cross sections. The Facility for Antiproton and Ion Research (FAIR) will offer unique, unprecedented opportunities to investigate many of the important reactions. The high yield of radioactive isotopes, even far away from the valley of stability, allows the investigation of isotopes involved in processes as exotic as the r or rp processes.
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| 10. |
- Indriolo, N., et al.
(författare)
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Herschel Survey of Galactic OH+, H2O+, and H3O+: Probing the Molecular Hydrogen Fraction and Cosmic-Ray Ionization Rate
- 2015
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Ingår i: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 800:1, s. 40-
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Tidskriftsartikel (refereegranskat)abstract
- In diffuse interstellar clouds the chemistry that leads to the formation of the oxygen-bearing ions OH+, H2O+, and H3O+ begins with the ionization of atomic hydrogen by cosmic rays, and continues through subsequent hydrogen abstraction reactions involving H2. Given these reaction pathways, the observed abundances of these molecules are useful in constraining both the total cosmic-ray ionization rate of atomic hydrogen (ζH) and molecular hydrogen fraction (f_H_2). We present observations targeting transitions of OH+, H2O+, and H3O+ made with the Herschel Space Observatory along 20 Galactic sight lines toward bright submillimeter continuum sources. Both OH+ and H2O+ are detected in absorption in multiple velocity components along every sight line, but H3O+ is only detected along 7 sight lines. From the molecular abundances we compute f_H_2 in multiple distinct components along each line of sight, and find a Gaussian distribution with mean and standard deviation 0.042 ± 0.018. This confirms previous findings that OH+ and H2O+ primarily reside in gas with low H2 fractions. We also infer ζH throughout our sample, and find a lognormal distribution with mean log (ζH) = –15.75 (ζH = 1.78 × 10–16 s–1) and standard deviation 0.29 for gas within the Galactic disk, but outside of the Galactic center. This is in good agreement with the mean and distribution of cosmic-ray ionization rates previously inferred from H_3^+ observations. Ionization rates in the Galactic center tend to be 10-100 times larger than found in the Galactic disk, also in accord with prior studies.
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