| 1. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
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| 3. |
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| 4. |
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| 5. |
- de Rojas, I., et al.
(författare)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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| 8. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 9. |
- Justice, A. E., et al.
(författare)
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Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
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| 12. |
- Abe, O, et al.
(författare)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Tidskriftsartikel (refereegranskat)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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| 13. |
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| 14. |
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| 15. |
- 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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| 16. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 17. |
- Psaridi, A., et al.
(författare)
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Discovery of two warm mini-Neptunes with contrasting densities orbiting the young K3V star TOI-815
- 2024
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 685
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Tidskriftsartikel (refereegranskat)abstract
- We present the discovery and characterization of two warm mini-Neptunes transiting the K3V star TOI-815 in a K–M binary system. Analysis of its spectra and rotation period reveal the star to be young, with an age of 200+−400200 Myr. TOI-815b has a 11.2-day period and a radius of 2.94 ± 0.05 R+ with transits observed by TESS, CHEOPS, ASTEP, and LCOGT. The outer planet, TOI-815c, has a radius of 2.62 ± 0.10 R+, based on observations of three nonconsecutive transits with TESS; targeted CHEOPS photometry and radial velocity follow-up with ESPRESSO were required to confirm the 35-day period. ESPRESSO confirmed the planetary nature of both planets and measured masses of 7.6 ± 1.5 M+ (ρP = 1.64+−003331 g cm−3) and 23.5 ± 2.4 M+ (ρP = 7.2+−1110 g cm−3), respectively. Thus, the planets have very different masses, which is unusual for compact multi-planet systems. Moreover, our statistical analysis of mini-Neptunes orbiting FGK stars suggests that weakly irradiated planets tend to have higher bulk densities compared to those undergoing strong irradiation. This could be ascribed to their cooler atmospheres, which are more compressed and denser. Internal structure modeling of TOI-815b suggests it likely has a H-He atmosphere that constitutes a few percent of the total planet mass, or higher if the planet is assumed to have no water. In contrast, the measured mass and radius of TOI-815c can be explained without invoking any atmosphere, challenging planetary formation theories. Finally, we infer from our measurements that the star is viewed close to pole-on, which implies a spin-orbit misalignment at the 3σ level. This emphasizes the peculiarity of the system’s orbital architecture, and probably hints at an eventful dynamical history.
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| 18. |
- Sartelli, Massimo, et al.
(författare)
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Ten golden rules for optimal antibiotic use in hospital settings: the WARNING call to action
- 2023
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Ingår i: WORLD JOURNAL OF EMERGENCY SURGERY. - 1749-7922. ; 18:1
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Forskningsöversikt (refereegranskat)abstract
- Antibiotics are recognized widely for their benefits when used appropriately. However, they are often used inappropriately despite the importance of responsible use within good clinical practice. Effective antibiotic treatment is an essential component of universal healthcare, and it is a global responsibility to ensure appropriate use. Currently, pharmaceutical companies have little incentive to develop new antibiotics due to scientific, regulatory, and financial barriers, further emphasizing the importance of appropriate antibiotic use. To address this issue, the Global Alliance for Infections in Surgery established an international multidisciplinary task force of 295 experts from 115 countries with different backgrounds. The task force developed a position statement called WARNING (Worldwide Antimicrobial Resistance National/International Network Group) aimed at raising awareness of antimicrobial resistance and improving antibiotic prescribing practices worldwide. The statement outlined is 10 axioms, or "golden rules," for the appropriate use of antibiotics that all healthcare workers should consistently adhere in clinical practice.
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| 19. |
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| 20. |
- Babusci, D., et al.
(författare)
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Precision measurement of sigma (e(+)e(-) -> pi(+)pi(-)gamma)/sigma(e(+)e(-) ->mu(+)mu(-)gamma) and determination of the pi(+)pi(-) contribution to the muon anomaly with the KLOE detector
- 2013
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 720:4-5, s. 336-343
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Tidskriftsartikel (refereegranskat)abstract
- We have measured the ratio cr (e(+)e(-) -> pi(+)pi(-)gamma)/sigma(e(+)e(-) -> mu(+)mu(-)gamma), with the KLOE detector at DA Phi NE for a total integrated luminosity of similar to 240 pb(-1). From this ratio we obtain the cross section sigma (e(+)e(-) -> pi(+)pi(-)gamma). From the cross section we determine the pion form factor vertical bar F-pi vertical bar(2) and the two-pion contribution to the muon anomaly a(mu) for 0.592< M-pi pi < 0.975 GeV, Delta(pi pi) a(mu) = (385.1 +/- 1.1(stat) +/- 2.7(sys+theo)) x 10(-10). This result confirms the current discrepancy between the Standard Model calculation and the experimental measurement of the muon anomaly. (c) 2013 Elsevier B.V. All rights reserved.
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| 21. |
- Babusci, D., et al.
(författare)
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A new limit on the CP violating decay K-S -> 3 pi(0) with the KLOE experiment
- 2013
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 723:1-3, s. 54-60
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Tidskriftsartikel (refereegranskat)abstract
- We have carried out a new direct search for the CP violating decay K-S -> 3 pi(0) with 1.7 fb(-1) of e(+)e(-) collisions collected by the KLOE detector at the Phi-factory DA Phi NE. We have searched for this decay in a sample of about 5.9 x 10(8) KSKL events tagging the K-S by means of the K-L interaction in the calorimeter and requiring six prompt photons. With respect to our previous search, the analysis has been improved by increasing of a factor four the tagged sample and by a more effective background rejection of fake K-S tags and spurious clusters. We find no candidates in data and simulated background samples, while we expect 0.12 standard model events. Normalizing to the number of K-S -> 2 pi(0) events in the same sample, we set the upper limit on BR(K-S -> 3 pi(0)) <= 2.6 x 10(-8) at 90% C.L., five times lower than the previous limit. We also set the upper limit on the eta(000) parameter, vertical bar eta(000)vertical bar <= 0.0088 at 90% C.L., improving by a factor two the latest direct measurement. (c) 2013 Elsevier B.V. All rights reserved.
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| 22. |
- Jung, Christian, et al.
(författare)
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A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
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Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
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| 23. |
- Babusci, D., et al.
(författare)
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Limit on the production of a light vector gauge boson in phi meson decays with the KLOE detector
- 2013
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 720:1-3, s. 111-115
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Tidskriftsartikel (refereegranskat)abstract
- We present a new limit on the production of a light dark-force mediator with the KLOE detector at DA Phi NE. This boson, called U, has been searched for in the decay phi -> eta U, U -> e(+)e(-), analyzing the. decay eta -> pi(0)pi(0)pi(0) in a data sample of 1.7 fb(-1). No structures are observed in the e(+)e(-) invariant mass distribution over the background. This search is combined with a previous result obtained from the decay eta -> pi(+)pi(-)pi(0), increasing the sensitivity. We set an upper limit at 90% C.L. on the ratio between the U boson coupling constant and the fine structure constant of alpha'/alpha < 1.7 x 10(-5) for 30 < M-U < 400 MeV and alpha'/alpha <= 8 x 10(-6) for the sub-region 50 < M-U <210 MeV. This result assumes the Vector Meson Dominance expectations for the phi eta gamma* transition form factor. The dependence of this limit on the transition form factor has also been studied.
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| 24. |
- Babusci, D., et al.
(författare)
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Measurement of eta meson production in gamma gamma interactions and Gamma(eta -> gamma gamma) with the KLOE detector
- 2013
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Ingår i: Journal of High Energy Physics (JHEP). - 1126-6708 .- 1029-8479. ; :1, s. 119-
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Tidskriftsartikel (refereegranskat)abstract
- We present a measurement of eta meson production in photon-photon interactions produced by electron-positron beams colliding with root s = 1 GeV. The measurement is done with the KLOE detector at the phi-factory DA Phi NE with an integrated luminosity of 0.24 fb(-1). The e(+)e(-) -> e(+)e(-)eta cross section is measured without detecting the outgoing electron and positron, selecting the decays eta -> pi(+)pi(-)pi(0) and eta -> pi(0)pi(0)pi(0). The most relevant background is due to e(+)e(-) -> eta gamma when the monochromatic photon escapes detection. The cross section for this process is measured as sigma(e(+)e(-) -> eta gamma) = (856 +/- 8(stat) +/- 16(syst)) pb. The combined result for the e(+)e(-) -> e(+)e(-)eta cross section is sigma(e(+)e(-) -> e(+)e(-)eta) = (32.72 +/- 1.27(stat) +/- 0.70(syst)) pb. From this we derive the partial width Gamma(eta -> gamma gamma) = (520 +/- 20(stat) +/- 13(syst)) eV. This is in agreement with the world average and is the most precise measurement to date.
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| 25. |
- Babusci, D., et al.
(författare)
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Test of CPT and Lorentz symmetry in entangled neutral kaons with the KLOE experiment
- 2014
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 730, s. 89-94
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Tidskriftsartikel (refereegranskat)abstract
- Neutral kaon pairs produced in phi decays in anti-symmetric entangled state can be exploited to search for violation of CPT symmetry and Lorentz invariance. We present an analysis of the CP-violating process phi -> KSKL -> pi(+)pi(-)pi(+)pi(-) based on 1.7 fb(-1) of data collected by the KLOE experiment at the Frascati phi-factory DA Phi NE. The data are used to perform a Measurement of the CPT-violating parameters Delta a(mu) for neutral kaons in the context of the Standard Model Extension framework. The parameters measured in the reference frame of the fixed stars are: Delta a(0) = (-6.0 +/- 7.7(stat)+/- 3.1(syst)) X 10(-18) GeV, Delta a(x) = (0.9 +/- 1.5(stat)+/- 0.6(syst)) X 10(-18) GeV, Delta a(y) = (-2.0 +/- 1.5(stat)+/- 0.5(syst)) X 10(-18) GeV, Delta a(z) = (3.1 +/- 1.7(stat)+/- 0.5(syst)) X 10(-18) GeV. These are presently the most precise measurements in the quark sector of the Standard Model Extension. (C) 2014 The Authors. Published by Elsevier B.V.
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| 26. |
- Koutoulaki, M., et al.
(författare)
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The GRAVITY young stellar object survey: IV. The CO overtone emission in 51 Oph at sub-au scales
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 645
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Tidskriftsartikel (refereegranskat)abstract
- Context. 51 Oph is a Herbig Ae/Be star that exhibits strong near-infrared CO ro-vibrational emission at 2.3 μm, most likely originating in the innermost regions of a circumstellar disc. Aims. We aim to obtain the physical and geometrical properties of the system by spatially resolving the circumstellar environment of the inner gaseous disc. Methods. We used the second-generation Very Large Telescope Interferometer instrument GRAVITY to spatially resolve the continuum and the CO overtone emission. We obtained data over 12 baselines with the auxiliary telescopes and derive visibilities, and the differential and closure phases as a function of wavelength. We used a simple local thermal equilibrium ring model of the CO emission to reproduce the spectrum and CO line displacements. Results. Our interferometric data show that the star is marginally resolved at our spatial resolution, with a radius of ∼10.58 ± 2.65R·. The K-band continuum emission from the disc is inclined by 63° ± 1°, with a position angle of 116° ± 1°, and 4 ± 0.8 mas (0.5 ± 0.1 au) across. The visibilities increase within the CO line emission, indicating that the CO is emitted within the dust-sublimation radius. By modelling the CO bandhead spectrum, we derive that the CO is emitted from a hot (T = 1900-2800 K) and dense (NCO = (0.9-9) × 1021 cm-2) gas. The analysis of the CO line displacement with respect to the continuum allows us to infer that the CO is emitted from a region 0.10 ± 0.02 au across, well within the dust-sublimation radius. The inclination and position angle of the CO line emitting region is consistent with that of the dusty disc. Conclusions. Our spatially resolved interferometric observations confirm the CO ro-vibrational emission within the dust-free region of the inner disc. Conventional disc models exclude the presence of CO in the dust-depleted regions of Herbig AeBe stars. Ad hoc models of the innermost disc regions, that can compute the properties of the dust-free inner disc, are therefore required.
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| 27. |
- Axfors, Cathrine, et al.
(författare)
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Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials
- 2021
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I-2=0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I-2=0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities. Hydroxychloroquine and chloroquine have been investigated as a potential treatment for Covid-19 in several clinical trials. Here the authors report a meta-analysis of published and unpublished trials, and show that treatment with hydroxychloroquine for patients with Covid-19 was associated with increased mortality, and there was no benefit from chloroquine.
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| 28. |
- Ebersole, Charles R., et al.
(författare)
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Many Labs 5: Testing Pre-Data-Collection Peer Review as an Intervention to Increase Replicability
- 2020
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Ingår i: Advances in Methods and Practices in Psychological Science. - : Sage. - 2515-2467 .- 2515-2459. ; 3:3, s. 309-331
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Tidskriftsartikel (refereegranskat)abstract
- Replication studies in psychological science sometimes fail to reproduce prior findings. If these studies use methods that are unfaithful to the original study or ineffective in eliciting the phenomenon of interest, then a failure to replicate may be a failure of the protocol rather than a challenge to the original finding. Formal pre-data-collection peer review by experts may address shortcomings and increase replicability rates. We selected 10 replication studies from the Reproducibility Project: Psychology (RP:P; Open Science Collaboration, 2015) for which the original authors had expressed concerns about the replication designs before data collection; only one of these studies had yielded a statistically significant effect (p < .05). Commenters suggested that lack of adherence to expert review and low-powered tests were the reasons that most of these RP:P studies failed to replicate the original effects. We revised the replication protocols and received formal peer review prior to conducting new replication studies. We administered the RP:P and revised protocols in multiple laboratories (median number of laboratories per original study = 6.5, range = 3-9; median total sample = 1,279.5, range = 276-3,512) for high-powered tests of each original finding with both protocols. Overall, following the preregistered analysis plan, we found that the revised protocols produced effect sizes similar to those of the RP:P protocols (Delta r = .002 or .014, depending on analytic approach). The median effect size for the revised protocols (r = .05) was similar to that of the RP:P protocols (r = .04) and the original RP:P replications (r = .11), and smaller than that of the original studies (r = .37). Analysis of the cumulative evidence across the original studies and the corresponding three replication attempts provided very precise estimates of the 10 tested effects and indicated that their effect sizes (median r = .07, range = .00-.15) were 78% smaller, on average, than the original effect sizes (median r = .37, range = .19-.50).
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| 29. |
- Lorenz, M. W., et al.
(författare)
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Predictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk - Results from the PROG-IMT collaboration
- 2018
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- Aims Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk. From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies. In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95-1.02) in group A, 0.98 (0.93-1.04) in group B, and 0.95 (0.89-1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07-1.23) in group A, 1.13 (1.05-1.22) in group B, and 1.12 (1.05-1.20) in group C. We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals.
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| 30. |
- Tiegs, Scott D., et al.
(författare)
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Global patterns and drivers of ecosystem functioning in rivers and riparian zones
- 2019
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Ingår i: Science Advances. - Washington : American Association of Advancement in Science. - 2375-2548. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- River ecosystems receive and process vast quantities of terrestrial organic carbon, the fate of which depends strongly on microbial activity. Variation in and controls of processing rates, however, are poorly characterized at the global scale. In response, we used a peer-sourced research network and a highly standardized carbon processing assay to conduct a global-scale field experiment in greater than 1000 river and riparian sites. We found that Earth's biomes have distinct carbon processing signatures. Slow processing is evident across latitudes, whereas rapid rates are restricted to lower latitudes. Both the mean rate and variability decline with latitude, suggesting temperature constraints toward the poles and greater roles for other environmental drivers (e.g., nutrient loading) toward the equator. These results and data set the stage for unprecedented "next-generation biomonitoring" by establishing baselines to help quantify environmental impacts to the functioning of ecosystems at a global scale.
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| 31. |
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| 32. |
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| 33. |
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| 34. |
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| 35. |
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| 36. |
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| 37. |
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| 38. |
- Babusci, D., et al.
(författare)
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Search for light vector boson production in e(+)e(-) -> mu(+)mu(-)gamma interactions with the KLOE experiment
- 2014
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 736, s. 459-464
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Tidskriftsartikel (refereegranskat)abstract
- We have searched for a light vector boson U, the possible carrier of a "dark force", with the KLOE detector at the DA Phi NE e(+)e(-) collider, motivated by astrophysical evidence for the presence of dark matter in the Universe. Using e(+)e(-) collisions collected with an integrated luminosity of 239.3 pb(-1), we look for a dimuon mass peak in the reaction e(+)e(-) -> mu(+)mu(-)gamma, corresponding to the decay U -> mu(+)mu(-). We find no evidence for a U vector boson signal. We set a 90% CL upper limit for the mixing parameter squared between the photon and the U boson of 1.6 x 10(-5) to 8.6 x 10(-7) for the mass region 520 < m(U) < 980 MeV.
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| 39. |
- Babusci, D., et al.
(författare)
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Study of the Dalitz decay phi -> eta e(+)e(-) with the KLOE detector
- 2015
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 742, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- We have studied the vector to pseudoscalar conversion decay phi -> eta e(+)e(-), with.. eta -> pi(0)pi(0)pi(0), with the KLOE detector at DA phi NE. The data set of 1.7 fb(-1) of e(+)e(-) collisions at root s similar to M-phi contains a clear conversion decay signal of similar to 31,000 events from which we measured a value of BR(phi -> eta e(+)e-) = (1.075 +/- 0.007 +/- 0.038) x 10(-4). The same sample is used to determine the transition form factor by a fit to the e(+)e(-) invariant mass spectrum, obtaining b(phi eta)=( 1.28 +/- 0.10(-0.08)(+0.09)) GeV-2, that improves by a factor of five the precision of the previous measurement and is in good agreement with VMD expectations.
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| 40. |
- Babuscih, D., et al.
(författare)
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Measurement of the absolute branching ratio of the K+ -> pi(+) pi(-) pi(+) (gamma) decay with the KLOE detector
- 2014
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 738, s. 128-133
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Tidskriftsartikel (refereegranskat)abstract
- The absolute branching ratio of the K+ -> pi(+) pi(-) pi(+) (gamma) decay, inclusive of final-state radiation, has been measured using similar to 17 million tagged K+ mesons collected with the KLOE detector at DA Phi NE, the Frascati phi-factory. The result is: BR(K+ -> pi(+) pi(-) pi(+) (gamma)) = 0.05565 +/- 0.00031(stat) +/- 0.00025(syst) a factor similar or equal to 5 more precise with respect to the previous result. This work completes the program of precision measurements of the dominant kaon branching ratios at KLOE.
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| 41. |
- Berendsen, A. A. M., et al.
(författare)
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Association of Adherence to a Healthy Diet with Cognitive Decline in European and American Older Adults: A Meta-Analysis within the CHANCES Consortium
- 2017
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 43:3-4, s. 215-227
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To examine the association between a healthy diet, assessed by the Healthy Diet Indicator (HDI), and cognitive decline in older adults. Methods: Data from 21,837 participants aged >= 55 years from 3 cohorts (Survey in Europe on Nutrition and the Elderly, a Concerted Action [SENECA], Rotterdam Study [RS], Nurses' Health Study [NHS]) were analyzed. HDI scores were based on intakes of saturated fatty acids, polyunsaturated fatty acids, mono-and disaccharides, protein, cholesterol, fruits and vegetables, and fiber. The Telephone Interview for Cognitive Status in NHS and Mini-Mental State Examination in RS and SENECA were used to assess cognitive function from multiple repeated measures. Using multivariable-adjusted, mixed linear regression, mean differences in annual rates of cognitive decline by HDI quintiles were estimated. Results: Multivariable-adjusted differences in rates in the highest versus the lowest HDI quintile were 0.01 (95% CI -0.01, 0.02) in NHS, 0.00 (95% CI -0.02, 0.01) in RS, and 0.00 (95% CI -0.05, 0.05) in SENECA with a pooled estimate of 0.00 (95% CI -0.01, 0.01), I-2 = 0%. Conclusions: A higher HDI score was not related to reduced rates of cognitive decline in European and American older adults. (C) 2017 The Author(s) Published by S. Karger AG, Basel
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| 42. |
- Garcia-Lopez, R., et al.
(författare)
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A measure of the size of the magnetospheric accretion region in TW Hydrae
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 584:7822, s. 547-550
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Tidskriftsartikel (refereegranskat)abstract
- Stars form by accreting material from their surrounding disks. There is a consensus that matter flowing through the disk is channelled onto the stellar surface by the stellar magnetic field. This is thought to be strong enough to truncate the disk close to the corotation radius, at which the disk rotates at the same rate as the star. Spectro-interferometric studies in young stellar objects show that hydrogen emission (a well known tracer of accretion activity) mostly comes from a region a few milliarcseconds across, usually located within the dust sublimation radius1–3. The origin of the hydrogen emission could be the stellar magnetosphere, a rotating wind or a disk. In the case of intermediate-mass Herbig AeBe stars, the fact that Brackett γ (Brγ) emission is spatially resolved rules out the possibility that most of the emission comes from the magnetosphere4–6 because the weak magnetic fields (some tenths of a gauss) detected in these sources7,8 result in very compact magnetospheres. In the case of T Tauri sources, their larger magnetospheres should make them easier to resolve. The small angular size of the magnetosphere (a few tenths of a milliarcsecond), however, along with the presence of winds9,10 make the interpretation of the observations challenging. Here we report optical long-baseline interferometric observations that spatially resolve the inner disk of the T Tauri star TW Hydrae. We find that the near-infrared hydrogen emission comes from a region approximately 3.5 stellar radii across. This region is within the continuum dusty disk emitting region (7 stellar radii across) and also within the corotation radius, which is twice as big. This indicates that the hydrogen emission originates in the accretion columns (funnel flows of matter accreting onto the star), as expected in magnetospheric accretion models, rather than in a wind emitted at much larger distance (more than one astronomical unit).
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| 43. |
- Jansen, Willemijn J, et al.
(författare)
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Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
- 2022
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
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Tidskriftsartikel (refereegranskat)abstract
- One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Alzheimer disease biomarkers detected on PET or in CSF.Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Among the 19097 participants (mean [SD] age, 69.1 [9.8] years; 10148 women [53.1%]) included, 10139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P=.04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P=.004), subjective cognitive decline (9%; 95% CI, 3%-15%; P=.005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P=.004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P=.18).This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
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| 44. |
- Lembrechts, Jonas J., et al.
(författare)
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SoilTemp : A global database of near-surface temperature
- 2020
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 26:11, s. 6616-6629
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Tidskriftsartikel (refereegranskat)abstract
- Current analyses and predictions of spatially explicit patterns and processes in ecology most often rely on climate data interpolated from standardized weather stations. This interpolated climate data represents long-term average thermal conditions at coarse spatial resolutions only. Hence, many climate-forcing factors that operate at fine spatiotemporal resolutions are overlooked. This is particularly important in relation to effects of observation height (e.g. vegetation, snow and soil characteristics) and in habitats varying in their exposure to radiation, moisture and wind (e.g. topography, radiative forcing or cold-air pooling). Since organisms living close to the ground relate more strongly to these microclimatic conditions than to free-air temperatures, microclimatic ground and near-surface data are needed to provide realistic forecasts of the fate of such organisms under anthropogenic climate change, as well as of the functioning of the ecosystems they live in. To fill this critical gap, we highlight a call for temperature time series submissions to SoilTemp, a geospatial database initiative compiling soil and near-surface temperature data from all over the world. Currently, this database contains time series from 7,538 temperature sensors from 51 countries across all key biomes. The database will pave the way toward an improved global understanding of microclimate and bridge the gap between the available climate data and the climate at fine spatiotemporal resolutions relevant to most organisms and ecosystem processes.
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| 45. |
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| 46. |
- Tschiderer, L., et al.
(författare)
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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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Ingår i: Journal of the American Heart Association (JAHA). - 2047-9980. ; 12:12
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Tidskriftsartikel (refereegranskat)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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| 47. |
- Anastasi, A., et al.
(författare)
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Limit on the production of a low-mass vector boson in e(+)e(-) -> U gamma, U -> e(+)e(-) with the KLOE experiment
- 2015
-
Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 750, s. 633-637
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Tidskriftsartikel (refereegranskat)abstract
- The existence of a new force beyond the Standard Model is compelling because it could explain several striking astrophysical observations which fail standard interpretations. We searched for the light vector mediator of this dark force, the U boson, with the KLOE detector at the DA Phi NE e(+)e(-) collider. Using an integrated luminosity of 1.54 fb(-1), we studied the process e(+)e(-) -> U gamma, with U -> e(+)e(-), using radiative return to search for a resonant peak in the dielectron invariant-mass distribution. We did not find evidence for a signal, and set a 90% CL upper limit on the mixing strength between the Standard Model photon and the dark photon, epsilon(2), at 10(-6)-10(-4) in the 5-520 MeV/c(2) mass range.
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| 48. |
- Anastasi, A., et al.
(författare)
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Limit on the production of a new vector boson in e+e− → Uγ, U → π+π− with the KLOE experiment
- 2016
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 757, s. 356-361
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Tidskriftsartikel (refereegranskat)abstract
- Abstract The recent interest in a light gauge boson in the framework of an extra U(1) symmetry motivates searches in the mass range below 1 GeV. We present a search for such a particle, the dark photon, in e + e − → U γ , U → π + π − based on 28 million e + e − → π + π − γ events collected at DAΦNE by the KLOE experiment. The π + π − production by initial-state radiation compensates for a loss of sensitivity of previous KLOE U → e + e − , μ + μ − searches due to the small branching ratios in the ρ – ω resonance region. We found no evidence for a signal and set a limit at 90% CL on the mixing strength between the photon and the dark photon, ε 2 , in the U mass range between 527 and 987 MeV . Above 700 MeV this new limit is more stringent than previous ones.
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| 49. |
- Anastasi, A., et al.
(författare)
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Measurement of the running of the fine structure constant below 1 GeV with the KLOE detector
- 2017
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Ingår i: Physics Letters B. - : ELSEVIER SCIENCE BV. - 0370-2693 .- 1873-2445. ; 767, s. 485-492
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Tidskriftsartikel (refereegranskat)abstract
- We have measured the running of the effective QED coupling constant alpha(s) in the time-like region 0.6 < root s < 0.975 GeV with the KLOE detector at DA Phi NE using the Initial-State Radiation process e(+) e(-) -> mu(+) mu(-)gamma. It represents the first measurement of the running of alpha(s) in this energy region. Our results show a more than 5 sigma significance of the hadronic contribution to the running of alpha(s), which is the strongest direct evidence both in time- and space-like regions achieved in a single measurement. By using the e(+) e(-) -> pi(+) pi(-) cross section measured by KLOE, the real and imaginary parts of the shift Delta alpha(s) have been extracted. From a fit of the real part of Delta alpha(s) and assuming the lepton universality the branching ratio BR(omega -> mu(+) mu(-)) = (6.6 +/- 1.4(stat) +/- 1.7(syst)) (.) 10 (5)has been determined.
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| 50. |
- Anastasi, A., et al.
(författare)
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Precision measurement of the η → π + π − π 0 Dalitz plot distribution with the KLOE detector
- 2016
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Ingår i: Journal of High Energy Physics (JHEP). - 1126-6708 .- 1029-8479. ; :5
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Tidskriftsartikel (refereegranskat)abstract
- Using 1.6 fb−1 of e + e − → ϕ → ηγ data collected with the KLOE detector at DAΦNE, the Dalitz plot distribution for the η → π + π − π 0 decay is studied with the world’s largest sample of ∼ 4.7 · 106 events. The Dalitz plot density is parametrized as a polynomial expansion up to cubic terms in the normalized dimensionless variables X and Y . The experiment is sensitive to all charge conjugation conserving terms of the expansion, including a gX 2 Y term. The statistical uncertainty of all parameters is improved by a factor two with respect to earlier measurements.
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