| 1. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
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| 3. |
- 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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| 4. |
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| 5. |
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| 6. |
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| 7. |
- 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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| 8. |
- Plompen, A. J. M., et al.
(författare)
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The joint evaluated fission and fusion nuclear data library, JEFF-3.3
- 2020
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Ingår i: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 56:7
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Forskningsöversikt (refereegranskat)abstract
- The joint evaluated fission and fusion nuclear data library 3.3 is described. New evaluations for neutron-induced interactions with the major actinides 235U, 238U and 239Pu, on 241Am and 23Na, 59Ni, Cr, Cu, Zr, Cd, Hf, W, Au, Pb and Bi are presented. It includes new fission yields, prompt fission neutron spectra and average number of neutrons per fission. In addition, new data for radioactive decay, thermal neutron scattering, gamma-ray emission, neutron activation, delayed neutrons and displacement damage are presented. JEFF-3.3 was complemented by files from the TENDL project. The libraries for photon, proton, deuteron, triton, helion and alpha-particle induced reactions are from TENDL-2017. The demands for uncertainty quantification in modeling led to many new covariance data for the evaluations. A comparison between results from model calculations using the JEFF-3.3 library and those from benchmark experiments for criticality, delayed neutron yields, shielding and decay heat, reveals that JEFF-3.3 performes very well for a wide range of nuclear technology applications, in particular nuclear energy.
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| 9. |
- Manry, Jérémy, et al.
(författare)
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The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies.
- 2022
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 119:21
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Tidskriftsartikel (refereegranskat)abstract
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.
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| 10. |
- Rodriguez-Tajes, C., et al.
(författare)
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Transfer reactions in inverse kinematics: An experimental approach for fission investigations
- 2014
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Ingår i: Physical Review C - Nuclear Physics. - 2469-9985 .- 2469-9993. ; 89:2
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Tidskriftsartikel (refereegranskat)abstract
- Inelastic and multinucleon transfer reactions between a U-238 beam, accelerated at 6.14 MeV/u, and a C-12 target were used for the production of neutron-rich, fissioning systems from U to Cm. A Si telescope, devoted to the detection of the targetlike nuclei, provided a characterization of the fissioning systems in atomic and mass numbers, as well as in excitation energy. Cross sections and angular and excitation-energy distributions were measured for the inelastic and transfer channels. Possible excitations of the targetlike nuclei were experimentally investigated for the first time, by means of gamma-ray measurements. The decays from the first excited states of 12C, B-11, and Be-10 were observed with probabilities of 0.12-0.14, while no evidence for the population of higher-lying states was found. Moreover, the fission probabilities of U-238, Np-239 and Pu-240,Pu-241,Pu-242 and Cm-244 were determined as a function of the excitation energy.
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| 11. |
- Ayyer, Kartik, et al.
(författare)
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3D diffractive imaging of nanoparticle ensembles using an x-ray laser
- 2021
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Ingår i: Optica. - : Optical Society of America. - 2334-2536. ; 8:1, s. 15-23
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Tidskriftsartikel (refereegranskat)abstract
- Single particle imaging at x-ray free electron lasers (XFELs) has the potential to determine the structure and dynamics of single biomolecules at room temperature. Two major hurdles have prevented this potential from being reached, namely, the collection of sufficient high-quality diffraction patterns and robust computational purification to overcome structural heterogeneity. We report the breaking of both of these barriers using gold nanoparticle test samples, recording around 10 million diffraction patterns at the European XFEL and structurally and orientationally sorting the patterns to obtain better than 3-nm-resolution 3D reconstructions for each of four samples. With these new developments, integrating advancements in x-ray sources, fast-framing detectors, efficient sample delivery, and data analysis algorithms, we illuminate the path towards sub-nano meter biomolecular imaging. The methods developed here can also be extended to characterize ensembles that are inherently diverse to obtain their full structural landscape. Published by The Optical Society under the terms of the Creative Commons Attribution 4.0 License.
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| 12. |
- Chen, H.Y., et al.
(författare)
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Dyslipidemia, inflammation, calcification, and adiposity in aortic stenosis: a genome-wide study
- 2023
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 44:21, s. 1927-1939
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Tidskriftsartikel (refereegranskat)abstract
- Aims Although highly heritable, the genetic etiology of calcific aortic stenosis (AS) remains incompletely understood. The aim of this study was to discover novel genetic contributors to AS and to integrate functional, expression, and cross-phenotype data to identify mechanisms of AS. Methods and results A genome-wide meta-analysis of 11.6 million variants in 10 cohorts involving 653 867 European ancestry participants (13 765 cases) was performed. Seventeen loci were associated with AS at P ≤ 5 × 10−8, of which 15 replicated in an independent cohort of 90 828 participants (7111 cases), including CELSR2–SORT1, NLRP6, and SMC2. A genetic risk score comprised of the index variants was associated with AS [odds ratio (OR) per standard deviation, 1.31; 95% confidence interval (CI), 1.26–1.35; P = 2.7 × 10−51] and aortic valve calcium (OR per standard deviation, 1.22; 95% CI, 1.08–1.37; P = 1.4 × 10−3), after adjustment for known risk factors. A phenome-wide association study indicated multiple associations with coronary artery disease, apolipoprotein B, and triglycerides. Mendelian randomization supported a causal role for apolipoprotein B-containing lipoprotein particles in AS (OR per g/L of apolipoprotein B, 3.85; 95% CI, 2.90–5.12; P = 2.1 × 10−20) and replicated previous findings of causality for lipoprotein(a) (OR per natural logarithm, 1.20; 95% CI, 1.17–1.23; P = 4.8 × 10−73) and body mass index (OR per kg/m2, 1.07; 95% CI, 1.05–1.9; P = 1.9 × 10−12). Colocalization analyses using the GTEx database identified a role for differential expression of the genes LPA, SORT1, ACTR2, NOTCH4, IL6R, and FADS. Conclusion Dyslipidemia, inflammation, calcification, and adiposity play important roles in the etiology of AS, implicating novel treatments and prevention strategies. © The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.
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| 13. |
- Look, M, et al.
(författare)
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Pooled analysis of prognostic impact of uPA and PAI-I in breast cancer patients
- 2003
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Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 90:3, s. 538-548
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Tidskriftsartikel (refereegranskat)abstract
- In this report we present an extension of the pooled analysis of the prognostic impact of urokinase-type plasminogen activator (uPA) and its inhibitor PAI-I in breast cancer patients. We analyzed a different endpoint, metastasis-free survival (MFS). We checked the consistency of the estimates for uPA and PAI-I for relapse-free survival (RFS) and MFS exploring possible sources of heterogeneity. Nodal status, the most important prognostic factor for breast cancer, introduced heterogeneity in the uPA/PAI-I survival analyses, reflecting the interaction between nodal status and uPA/PAI-I. The estimates for uPA and PAI-I were found to be consistent, even when a different transformation of their values was used. The heterogeneity of the separate data sets decreased if the levels of uPA and PAI-I were ranked, data sets were pooled, and the analyses corrected for the base model that included all traditional prognostic factors, and stratified by data set. We conclude that uPA and PAI-I are ready to be used in the clinic to help classify breast cancer patients into high and low risk groups.
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| 14. |
- Look, MP, et al.
(författare)
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Pooled analysis of prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 8377 breast cancer patients
- 2002
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 94:2, s. 116-128
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Tidskriftsartikel (refereegranskat)abstract
- Background: Urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) play essential roles in tumor invasion and metastasis. High levels of both uPA and PAT-1 are associated with poor prognosis in breast cancer patients. To confirm the prognostic value of uPA and PAI-1 in primary breast cancer, we reanalyzed individual patient data provided by members of the European Organization for Research and Treatment of Cancer-Receptor and Biomarker Group (EORTC-RBG). Methods: The study included 18 datasets involving 8377 breast cancer patients. During follow-up (median 79 months), 35% of the patients relapsed and 27% died. Levels of uPA and PAI-1 in tumor tissue extracts were determined by different immunoassays; values were ranked within each dataset and divided by the number of patients in that dataset to produce fractional ranks that could be compared directly across datasets. Associations of ranks of uPA and PAI-1 levels with relapse-free survival (RFS) and overall survival (OS) were analyzed by Cox multivariable regression analysis stratified by dataset, including the following traditional prognostic variables: age, menopausal status, lymph node status, tumor size, histologic grade, and steroid hormone-receptor status. All P values were two-sided. Results: Apart from lymph node status, high levels of uPA and PAI-1 were the strongest predictors of both poor RFS and poor OS in the analyses of all patients. Moreover, in both lymph node-positive and lymph nodenegative patients, higher uPA and PAI-1 values were independently associated with poor RFS and poor OS. For (untreated) lymph node-negative patients in particular, uPA and PAI-1 included together showed strong prognostic ability (all P<.001). Conclusions: This pooled analysis of the EORTC-RBG datasets confirmed the strong and independent prognostic value of uPA and PAI-1 in primary breast cancer. For patients with lymph node-negative breast cancer, uPA and PAI-1 measurements in primary tumors may be especially useful for designing individualized treatment strategies.
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| 15. |
- Reulen, Raoul C, et al.
(författare)
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Risk Factors for Primary Bone Cancer After Childhood Cancer : A PanCare Childhood and Adolescent Cancer Survivor Care and Follow-Up Studies Nested Case-Control Study
- 2023
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Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 41:21, s. 3735-3746
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Radiation to the bone and exposure to alkylating agents increases the risk of bone cancer among survivors of childhood cancer, but there is uncertainty regarding the risks of bone tissue radiation doses below 10 Gy and the dose-response relationship for specific types of chemotherapy.METHODS: Twelve European countries contributed 228 cases and 228 matched controls to a nested case-control study within a cohort of 69,460 5-year survivors of childhood cancer. Odds ratios (ORs) of developing bone cancer for different levels of cumulative radiation exposure and cumulative doses of specific types of chemotherapy were calculated. Excess ORs were calculated to investigate the shape and extent of any dose-response relationship.RESULTS: The OR associated with bone tissue exposed to 1-4 Gy was 4.8-fold (95% CI, 1.2 to 19.6) and to 5-9 Gy was 9.6-fold (95% CI, 2.4 to 37.4) compared with unexposed bone tissue. The OR increased linearly with increasing dose of radiation ( P trend < .001) up to 78-fold (95% CI, 9.2 to 669.9) for doses of ≥40 Gy. For cumulative alkylating agent doses of 10,000-19,999 and ≥20,000 mg/m 2, the radiation-adjusted ORs were 7.1 (95% CI, 2.2 to 22.8) and 8.3 (95% CI, 2.8 to 24.4), respectively, with independent contributions from each of procarbazine, ifosfamide, and cyclophosphamide. Other cytotoxics were not associated with bone cancer. CONCLUSION: To our knowledge, we demonstrate-for the first time-that the risk of bone cancer is increased 5- to 10-fold after exposure of bone tissue to cumulative radiation doses of 1-9 Gy. Alkylating agents exceeding 10,000 mg/m 2 increase the risk 7- to 8-fold, particularly following procarbazine, ifosfamide, and cyclophosphamide. These substantially elevated risks should be used to develop/update clinical follow-up guidelines and survivorship care plans.
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| 16. |
- Sobolev, Egor, et al.
(författare)
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Megahertz single-particle imaging at the European XFEL
- 2020
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Ingår i: Communications Physics. - : Springer Science and Business Media LLC. - 2399-3650. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- The emergence of high repetition-rate X-ray free-electron lasers (XFELs) powered by superconducting accelerator technology enables the measurement of significantly more experimental data per day than was previously possible. The European XFEL is expected to provide 27,000 pulses per second, over two orders of magnitude more than any other XFEL. The increased pulse rate is a key enabling factor for single-particle X-ray diffractive imaging, which relies on averaging the weak diffraction signal from single biological particles. Taking full advantage of this new capability requires that all experimental steps, from sample preparation and delivery to the acquisition of diffraction patterns, are compatible with the increased pulse repetition rate. Here, we show that single-particle imaging can be performed using X-ray pulses at megahertz repetition rates. The results obtained pave the way towards exploiting high repetition-rate X-ray free-electron lasers for single-particle imaging at their full repetition rate.
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| 17. |
- Svantesson, Eleonor, et al.
(författare)
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Clinical Outcomes After Anterior Cruciate Ligament Injury: Panther Symposium ACL Injury Clinical Outcomes Consensus Group.
- 2020
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Ingår i: Orthopaedic journal of sports medicine. - 2325-9671. ; 8:7
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Tidskriftsartikel (refereegranskat)abstract
- A stringent outcome assessment is a key aspect of establishing evidence-based clinical guidelines for anterior cruciate ligament (ACL) injury treatment. To establish a standardized assessment of clinical outcome after ACL treatment, a consensus meeting including a multidisciplinary group of ACL experts was held at the ACL Consensus Meeting Panther Symposium, Pittsburgh, Pennsylvania, USA, in June 2019. The aim was to establish a consensus on what data should be reported when conducting an ACL outcome study, what specific outcome measurements should be used, and at what follow-up time those outcomes should be assessed. The group reached consensus on 9 statements by using a modified Delphi method. In general, outcomes after ACL treatment can be divided into 4 robust categories: early adverse events, patient-reported outcomes (PROs), ACL graft failure/recurrent ligament disruption, and clinical measures of knee function and structure. A comprehensive assessment after ACL treatment should aim to provide a complete overview of the treatment result, optimally including the various aspects of outcome categories. For most research questions, a minimum follow-up of 2 years with an optimal follow-up rate of 80% is necessary to achieve a comprehensive assessment. This should include clinical examination, any sustained reinjuries, validated knee-specific PROs, and health-related quality of life questionnaires. In the midterm to long-term follow-up, the presence of osteoarthritis should be evaluated. This consensus paper provides practical guidelines for how the aforementioned entities of outcomes should be reported and suggests the preferred tools for a reliable and valid assessment of outcome after ACL treatment.
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| 18. |
- Tran, Thao Thanh, et al.
(författare)
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Inhibition of the master regulator of Listeria monocytogenes virulence enables bacterial clearance from spacious replication vacuoles in infected macrophages
- 2022
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Ingår i: PLoS Pathogens. - : Public Library Science. - 1553-7366 .- 1553-7374. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- A hallmark of Listeria (L.) monocytogenes pathogenesis is bacterial escape from maturing entry vacuoles, which is required for rapid bacterial replication in the host cell cytoplasm and cell-to-cell spread. The bacterial transcriptional activator PrfA controls expression of key virulence factors that enable exploitation of this intracellular niche. The transcriptional activity of PrfA within infected host cells is controlled by allosteric coactivation. Inhibitory occupation of the coactivator site has been shown to impair PrfA functions, but consequences of PrfA inhibition for L. monocytogenes infection and pathogenesis are unknown. Here we report the crystal structure of PrfA with a small molecule inhibitor occupying the coactivator site at 2.0 Å resolution. Using molecular imaging and infection studies in macrophages, we demonstrate that PrfA inhibition prevents the vacuolar escape of L. monocytogenes and enables extensive bacterial replication inside spacious vacuoles. In contrast to previously described spacious Listeria-containing vacuoles, which have been implicated in supporting chronic infection, PrfA inhibition facilitated progressive clearance of intracellular L. monocytogenes from spacious vacuoles through lysosomal degradation. Thus, inhibitory occupation of the PrfA coactivator site facilitates formation of a transient intravacuolar L. monocytogenes replication niche that licenses macrophages to effectively eliminate intracellular bacteria. Our findings encourage further exploration of PrfA as a potential target for antimicrobials and highlight that intra-vacuolar residence of L. monocytogenes in macrophages is not inevitably tied to bacterial persistence.
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| 19. |
- Wiedorn, Max O., et al.
(författare)
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Megahertz serial crystallography
- 2018
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The new European X-ray Free-Electron Laser is the first X-ray free-electron laser capable of delivering X-ray pulses with a megahertz inter-pulse spacing, more than four orders of magnitude higher than previously possible. However, to date, it has been unclear whether it would indeed be possible to measure high-quality diffraction data at megahertz pulse repetition rates. Here, we show that high-quality structures can indeed be obtained using currently available operating conditions at the European XFEL. We present two complete data sets, one from the well-known model system lysozyme and the other from a so far unknown complex of a beta-lactamase from K. pneumoniae involved in antibiotic resistance. This result opens up megahertz serial femtosecond crystallography (SFX) as a tool for reliable structure determination, substrate screening and the efficient measurement of the evolution and dynamics of molecular structures using megahertz repetition rate pulses available at this new class of X-ray laser source.
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| 20. |
- Abercrombie, Daniel, et al.
(författare)
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Dark Matter benchmark models for early LHC Run-2 Searches : Report of the ATLAS/CMS Dark Matter Forum
- 2020
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Ingår i: Physics of the Dark Universe. - : Elsevier BV. - 2212-6864. ; 27
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Tidskriftsartikel (refereegranskat)abstract
- This document is the final report of the ATLAS-CMS Dark Matter Forum, a forum organized by the ATLAS and CMS collaborations with the participation of experts on theories of Dark Matter, to select a minimal basis set of dark matter simplified models that should support the design of the early LHC Run-2 searches. A prioritized, compact set of benchmark models is proposed, accompanied by studies of the parameter space of these models and a repository of generator implementations. This report also addresses how to apply the Effective Field Theory formalism for collider searches and present the results of such interpretations.
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| 21. |
- Andrews, Timothy, et al.
(författare)
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On the Effect of Historical SST Patterns on Radiative Feedback
- 2022
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Ingår i: Journal of Geophysical Research - Atmospheres. - 2169-897X .- 2169-8996. ; 127:18
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Tidskriftsartikel (refereegranskat)abstract
- We investigate the dependence of radiative feedback on the pattern of sea-surface temperature (SST) change in 14 Atmospheric General Circulation Models (AGCMs) forced with observed variations in SST and sea-ice over the historical record from 1871 to near-present. We find that over 1871–1980, the Earth warmed with feedbacks largely consistent and strongly correlated with long-term climate sensitivity feedbacks (diagnosed from corresponding atmosphere-ocean GCM abrupt-4xCO2 simulations). Post 1980, however, the Earth warmed with unusual trends in tropical Pacific SSTs (enhanced warming in the west, cooling in the east) and cooling in the Southern Ocean that drove climate feedback to be uncorrelated with—and indicating much lower climate sensitivity than—that expected for long-term CO2 increase. We show that these conclusions are not strongly dependent on the Atmospheric Model Intercomparison Project (AMIP) II SST data set used to force the AGCMs, though the magnitude of feedback post 1980 is generally smaller in nine AGCMs forced with alternative HadISST1 SST boundary conditions. We quantify a “pattern effect” (defined as the difference between historical and long-term CO2 feedback) equal to 0.48 ± 0.47 [5%–95%] W m−2 K−1 for the time-period 1871–2010 when the AGCMs are forced with HadISST1 SSTs, or 0.70 ± 0.47 [5%–95%] W m−2 K−1 when forced with AMIP II SSTs. Assessed changes in the Earth's historical energy budget agree with the AGCM feedback estimates. Furthermore satellite observations of changes in top-of-atmosphere radiative fluxes since 1985 suggest that the pattern effect was particularly strong over recent decades but may be waning post 2014.
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| 22. |
- Bagwell, C B, et al.
(författare)
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Optimizing flow cytometric DNA ploidy and S-phase fraction as independent prognostic markers for node-negative breast cancer specimens
- 2001
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Ingår i: Cytometry. - : Wiley. - 0196-4763 .- 1097-0320. ; 46:3, s. 121-135
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Tidskriftsartikel (refereegranskat)abstract
- Developing a reliable and quantitative assessment of the potential virulence of a malignancy has been a long-standing goal in clinical cytometry. DNA histogram analysis provides valuable information on the cycling activity of a tumor population through S-phase estimates; it also identifies nondiploid populations, a possible indicator of genetic instability and subsequent predisposition to metastasis. Because of conflicting studies in the literature, the clinical relevance of both of these potential prognostic markers has been questioned for the management of breast cancer patients. The purposes of this study are to present a set of 10 adjustments derived from a single large study that optimizes the prognostic strength of both DNA ploidy and S-phase and to test the validity of this approach on two other large multicenter studies. Ten adjustments to both DNA ploidy and S-phase were developed from a single node-negative breast cancer database from Baylor College (n = 961 cases). Seven of the adjustments were used to reclassify histograms into low-risk and high-risk ploidy patterns based on aneuploid fraction and DNA index optimum thresholds resulting in prognostic P values changing from little (P < 0.02) or no significance to P < 0.000005. Other databases from Sweden (n = 210 cases) and France (n = 220 cases) demonstrated similar improvement of DNA ploidy prognostic significance, P < 0.02 to P < 0.0009 and P < 0.12 to P < 0.002, respectively. Three other adjustments were applied to diploid and aneuploid S-phases. These adjustments eliminated a spurious correlation between DNA ploidy and S-phase and enabled them to combine independently into a powerful prognostic model capable of stratifying patients into low, intermediate, and high-risk groups (P < 0.000005). When the Baylor prognostic model was applied to the Sweden and French databases, similar significant patient stratifications were observed (P < 0.0003 and P < 0.00001, respectively). The successful transference of the Baylor prognostic model to other studies suggests that the proposed adjustments may play an important role in standardizing this test and provide valuable prognostic information to those involved in the management of breast cancer patients.
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| 23. |
- Bastard, Paul, et al.
(författare)
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Preexisting autoantibodies to type I IFNs underlie critical COVID-19 pneumonia in patients with APS-1.
- 2021
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Ingår i: The Journal of experimental medicine. - 1540-9538. ; 218:7
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Tidskriftsartikel (refereegranskat)abstract
- Patients with biallelic loss-of-function variants of AIRE suffer from autoimmune polyendocrine syndrome type-1 (APS-1) and produce a broad range of autoantibodies (auto-Abs), including circulating auto-Abs neutralizing most type I interferons (IFNs). These auto-Abs were recently reported to account for at least 10% of cases of life-threatening COVID-19 pneumonia in the general population. We report 22 APS-1 patients from 21 kindreds in seven countries, aged between 8 and 48 yr and infected with SARS-CoV-2 since February 2020. The 21 patients tested had auto-Abs neutralizing IFN-α subtypes and/or IFN-ω; one had anti-IFN-β and another anti-IFN-ε, but none had anti-IFN-κ. Strikingly, 19 patients (86%) were hospitalized for COVID-19 pneumonia, including 15 (68%) admitted to an intensive care unit, 11 (50%) who required mechanical ventilation, and four (18%) who died. Ambulatory disease in three patients (14%) was possibly accounted for by prior or early specific interventions. Preexisting auto-Abs neutralizing type I IFNs in APS-1 patients confer a very high risk of life-threatening COVID-19 pneumonia at any age.
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| 24. |
- Beaufils, Philipp, et al.
(författare)
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Reprint of : Surgical management of degenerative meniscus lesions: The 2016 ESSKA meniscus consensus
- 2017
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Ingår i: Sports Orthopaedics and Traumatology. - : Elsevier BV. - 0949-328X. ; 33:3, s. 293-304
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: A degenerative meniscus lesion is a slowly developing process typically involving a horizontal cleavage in a middle-aged or older person. When the knee is symptomatic, arthroscopic partial meniscectomy has been practised for a long time with many case series reporting improved patient outcomes. Since 2002, several randomised clinical trials demonstrated no additional benefit of arthroscopic partial meniscectomy compared to nonoperative treatment, sham surgery or sham arthroscopic partial meniscectomy. These results introduced controversy in the medical community and made clinical decision-making challenging in the daily clinical practice. To facilitate the clinical decision-making process, a consensus was developed. This initiative was endorsed by ESSKA. Methods: A degenerative meniscus lesion was defined as a lesion occurring without any history of significant acute trauma in a patient older than 35 years. Congenital lesions, traumatic meniscus tears and degenerative lesions occurring in young patients, especially in athletes, were excluded. The project followed the so-called formal consensus process, involving a steering group, a rating group and a peer-review group. A total of 84 surgeons and scientists from 22 European countries were included in the process. Twenty questions, their associated answers and an algorithm based on extensive literature review and clinical expertise, were proposed. Each question and answer set was graded according to the scientific level of the corresponding literature. Results: The main finding was that arthroscopic partial meniscectomy should not be proposed as a first line oftreatment for degenerative meniscus lesions. Arthroscopic partial meniscectomy should only be considered after a proper standardised clinical and radiological evaluation and when the response to non-operative management has not been satisfactory. Magnetic resonance imaging of the knee is typically not indicated in the first-line work-up, but knee radiography should be used as an imaging tool to support a diagnosis of osteoarthritis or to detect certain rare pathologies, such as tumours or fractures of the knee. Discussion: The present work offers a clear framework for the management of degenerative meniscus lesions, with the aim to balance information extracted from the scientific evidence and clinical expertise. Because of biases and weaknesses of the current literature and lack of definition of important criteria such as mechanical symptoms, it cannot be considered as an exact treatment algorithm. It summarises the results of the "ESSKA Meniscus Consensus Project" (http://www.esska.org/education/projects) and is the first official European consensus on this topic. The consensus may be updated and refined as more high-quality evidence emerges. Level of evidence: I.
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| 25. |
- Bowden, John A., et al.
(författare)
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Harmonizing lipidomics : NIST interlaboratory comparison exercise for lipidomics using SRM 1950-Metabolites in Frozen Human Plasma
- 2017
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Ingår i: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 58:12, s. 2275-2288
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Tidskriftsartikel (refereegranskat)abstract
- As the lipidomics field continues to advance, self-evaluation within the community is critical. Here, we performed an interlaboratory comparison exercise for lipidomics using Standard Reference Material (SRM) 1950-Metabolites in Frozen Human Plasma, a commercially available reference material. The interlaboratory study comprised 31 diverse laboratories, with each laboratory using a different lipidomics workflow. A total of 1,527 unique lipids were measured across all laboratories and consensus location estimates and associated uncertainties were determined for 339 of these lipids measured at the sum composition level by five or more participating laboratories. These evaluated lipids detected in SRM 1950 serve as community-wide benchmarks for intra-and interlaboratory quality control and method validation. These analyses were performed using nonstandardized laboratory-independent workflows. The consensus locations were also compared with a previous examination of SRM 1950 by the LIPID MAPS consortium.jlr While the central theme of the interlaboratory study was to provide values to help harmonize lipids, lipid mediators, and precursor measurements across the community, it was also initiated to stimulate a discussion regarding areas in need of improvement.
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| 26. |
- Brette, Romain, et al.
(författare)
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Simulation of networks of spiking neurons : A review of tools and strategies
- 2007
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Ingår i: Journal of Computational Neuroscience. - : Springer Science and Business Media LLC. - 0929-5313 .- 1573-6873. ; 23:3, s. 349-398
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Forskningsöversikt (refereegranskat)abstract
- We review different aspects of the simulation of spiking neural networks. We start by reviewing the different types of simulation strategies and algorithms that are currently implemented. We next review the precision of those simulation strategies, in particular in cases where plasticity depends on the exact timing of the spikes. We overview different simulators and simulation environments presently available (restricted to those freely available, open source and documented). For each simulation tool, its advantages and pitfalls are reviewed, with an aim to allow the reader to identify which simulator is appropriate for a given task. Finally, we provide a series of benchmark simulations of different types of networks of spiking neurons, including Hodgkin-Huxley type, integrate-and-fire models, interacting with current-based or conductance-based synapses, using clock-driven or event-driven integration strategies. The same set of models are implemented on the different simulators, and the codes are made available. The ultimate goal of this review is to provide a resource to facilitate identifying the appropriate integration strategy and simulation tool to use for a given modeling problem related to spiking neural networks.
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| 27. |
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| 28. |
- Corpas, Javier, et al.
(författare)
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Interplay between the Directing Group and Multifunctional Acetate Ligand in Pd-Catalyzed anti-Acetoxylation of Unsymmetrical Dialkyl-Substituted Alkynes
- 2022
-
Ingår i: ACS Catalysis. - : American Chemical Society (ACS). - 2155-5435. ; 12:11, s. 6596-6605
-
Tidskriftsartikel (refereegranskat)abstract
- The cooperative action of the acetate ligand, the 2-pyridyl sulfonyl (SO2Py) directing group on the alkyne substrate,and the palladium catalyst has been shown to be crucial forcontrolling reactivity, regioselectivity, and stereoselectivity in theacetoxylation of unsymmetrical internal alkynes under mildreaction conditions. The corresponding alkenyl acetates wereobtained in good yields with complete levels of beta-regioselectivityandanti-acetoxypalladation stereocontrol. Experimental andcomputational analyses provide insight into the reasons behindthis delicate interplay between the ligand, directing group, and themetal in the reaction mechanism. In fact, these studies unveil themultiple important roles of the acetate ligand in the coordinationsphere at the Pd center: (i) it brings the acetic acid reagent into close proximity to the metal to allow the simultaneous activation ofthe alkyne and the acetic acid, (ii) it serves as an inner-sphere base while enhancing the nucleophilicity of the acid, and (iii) it acts asan intramolecular acid to facilitate protodemetalation and regeneration of the catalyst. Further insight into the origin of the observedregiocontrol is provided by the mapping of potential energy profiles and distortion-interaction analysis
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| 29. |
- Diermeier, Theresa, et al.
(författare)
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Treatment After Anterior Cruciate Ligament Injury: Panther Symposium ACL Treatment Consensus Group
- 2020
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Ingår i: Orthopaedic Journal of Sports Medicine. - 2325-9671. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Treatment strategies for anterior cruciate ligament (ACL) injuries continue to evolve. Evidence supporting best-practice guidelines for the management of ACL injury is to a large extent based on studies with low-level evidence. An international consensus group of experts was convened to collaboratively advance toward consensus opinions regarding the best available evidence on operative versus nonoperative treatment for ACL injury. The purpose of this study was to report the consensus statements on operative versus nonoperative treatment of ACL injuries developed at the ACL Consensus Meeting Panther Symposium 2019. There were 66 international experts on the management of ACL injuries, representing 18 countries, who were convened and participated in a process based on the Delphi method of achieving consensus. Proposed consensus statements were drafted by the scientific organizing committee and session chairs for the 3 working groups. Panel participants reviewed preliminary statements before the meeting and provided initial agreement and comments on the statement via online survey. During the meeting, discussion and debate occurred for each statement, after which a final vote was then held. Ultimately, 80% agreement was defined a priori as consensus. A total of 11 of 13 statements on operative versus nonoperative treatment of ACL injury reached consensus during the symposium. Overall, 9 statements achieved unanimous support, 2 reached strong consensus, 1 did not achieve consensus, and 1 was removed because of redundancy in the information provided. In highly active patients engaged in jumping, cutting, and pivoting sports, early anatomic ACL reconstruction is recommended because of the high risk of secondary meniscal and cartilage injuries with delayed surgery, although a period of progressive rehabilitation to resolve impairments and improve neuromuscular function is recommended. For patients who seek to return to straight-plane activities, nonoperative treatment with structured, progressive rehabilitation is an acceptable treatment option. However, with persistent functional instability, or when episodes of giving way occur, anatomic ACL reconstruction is indicated. The consensus statements derived from international leaders in the field will assist clinicians in deciding between operative and nonoperative treatment with patients after an ACL injury.
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| 30. |
- Dorschel, Boris, et al.
(författare)
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The International Bathymetric Chart of the Southern Ocean Version 2
- 2022
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- The Southern Ocean surrounding Antarctica is a region that is key to a range of climatic and oceanographic processes with worldwide effects, and is characterised by high biological productivity and biodiversity. Since 2013, the International Bathymetric Chart of the Southern Ocean (IBCSO) has represented the most comprehensive compilation of bathymetry for the Southern Ocean south of 60 degrees S. Recently, the IBCSO Project has combined its efforts with the Nippon Foundation - GEBCO Seabed 2030 Project supporting the goal of mapping the world's oceans by 2030. New datasets initiated a second version of IBCSO (IBCSO v2). This version extends to 50 degrees S (covering approximately 2.4 times the area of seafloor of the previous version) including the gateways of the Antarctic Circumpolar Current and the Antarctic circumpolar frontal systems. Due to increased (multibeam) data coverage, IBCSO v2 significantly improves the overall representation of the Southern Ocean seafloor and resolves many submarine landforms in more detail. This makes IBCSO v2 the most authoritative seafloor map of the area south of 50 degrees S.
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| 31. |
- Garnier, Romain, et al.
(författare)
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Length of intervals between epidemics: evaluating the influence of maternal transfer of immunity
- 2014
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Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 4:5, s. 568-575
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Tidskriftsartikel (refereegranskat)abstract
- The length of intervals between epidemic outbreaks of infectious diseases is critical in epidemiology. In several species of marine mammals and birds, it is pivotal to also consider the life history of the species of concern, as the contact rate between individuals can have a seasonal flux, for example, due to aggregations during the breeding season. Recently, particular interest has been given to the role of the dynamics of immunity in determining the intervals between epidemics in wild animal populations. One potentially powerful, but often neglected, process in this context is the maternal transfer of immunity. Here, we explore theoretically how the transfer of maternal antibodies can delay the recurrence of epidemics using Phocine Distemper in harbor seals as an example of a system in which epidemic outbreaks are followed by pathogen extinction. We show that the presence of temporarily protected newborns can significantly increase the predicted interval between epidemics, and this effect is strongly dependent on the degree of synchrony in the breeding season. Furthermore, we found that stochasticity in the onset of epidemics in combination with maternally acquired immunity increases the predicted intervals between epidemics even more. These effects arise because newborns with maternal antibodies temporarily boost population level immunity above the threshold of herd immunity, particularly when breeding is synchronous. Overall, our results show that maternal antibodies can have a profound influence on the dynamics of wildlife epidemics, notably in gregarious species such as many marine mammals and seabirds.
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| 32. |
- Gojon, Romain, et al.
(författare)
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Azimuthal organisation of turbulent structures in underexpanded impinging round jets
- 2016
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Ingår i: 22nd AIAA/CEAS Aeroacoustics Conference, 2016. - Reston, Virginia : American Institute of Aeronautics and Astronautics. - 9781624103865
-
Konferensbidrag (refereegranskat)abstract
- The azimuthal organisation of the turbulent structures in underexpanded round jets impinging on a flat plate have been investigated using compressible large eddy simulation. The jet shear-layer region, as well as the region of the wall jets created on the plate after the impact are considered. The jets are characterized by a Nozzle Pressure Ratio of 4.03, a fully expanded Mach number of 1.56, and a Reynolds number of 6 × 104. The distance between the nozzle and the plate varies from 4.16r0 to 9.32r0. The jets generate acoustic tones due to a feedback mechanism. In this paper, the near pressure and density fields of the jets are analysed using Fast Fourier Transform on the nozzle exit plane, the plate, and an azimuthal plane. The amplitude and the phase fields on these sections at the tone frequencies are represented. Similar organisations of the turbulent structures are found in the jet shear layers and the wall jets. Thus, axisymmetric and helical arrangements of the structures in the shear layers lead to spiral and concentric distributions of the structures on the plate, respectively. In particular, for one of the jets, a spiral shape and concentric rings, associated with two tone frequencies generated simultaneously, are observed on the flat plate in the pressure and density phase fields. Moreover, the convection velocity of the turbulent structures on the plate is evaluated from the phase fields. Several diameters away from the jet axis, the velocities found for the present jets compare well with those found experimentally in the phase-averaged distributions of fluctuating pressure for impinging ideally expanded jets using fast-response Pressure-Sensitive Paint. Near the jet axis, given that the present jets are underexpanded, differences are observed, due to the presence of shock cell structures in the jets. Finally, the convection velocity of the turbulent structures on the wall are estimated from cross-correlations of radial velocity. The values obtained compare well with those determined from the phase fields.
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| 33. |
- Gojon, Romain, et al.
(författare)
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Investigation of the feedback mechanism in ideally expanded round impinging jets using large-eddy simulation
- 2016
-
Ingår i: 22nd AIAA/CEAS Aeroacoustics Conference, 2016. - Reston, Virginia : American Institute of Aeronautics and Astronautics.
-
Konferensbidrag (refereegranskat)abstract
- Large-eddy simulations (LES) have been performed in order to study the tone generation mechanism in four supersonic ideally expanded round impinging jets. The jets have a Mach number of 1.5, and a Reynolds number of 6 × 104. They impinge normally on a flat plate located at a distance from the nozzle exit varying from 6r0 up to 12r0 where r0 is the jet nozzle radius. The aerodynamic properties of the jets are first investigated. In particular, the convection velocity of the turbulent structures in the jet shear layers is computed. In the spectra of pressure fluctuations in the vicinity of the nozzle exit, intense tones emerge. Their associated Strouhal numbers are in agreement with measurements available for round impinging jets with similar exit conditions. The tone frequencies also correspond well to the frequencies predicted by the classical model of the aeroacoustic feedback establishing between the nozzle lips and the flat plate. A study of the feedback mechanism is then proposed by applying Fourier decomposition to the near pressure fields. The feedback mechanism is found to lead to the formation of hydrodynamic-acoustic standing waves. Moreover, for each tone frequency, the corresponding axisymmetric or helical oscillation mode of the jet is examined. Finally, an analysis is conducted using a vortex sheet model of the jet in order to determine the allowable frequency ranges of the upstream-propagating neutral acoustic wave modes. The tone frequencies obtained in the LES fall within these ranges, depending on their axisymmetric or helical nature.
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| 34. |
- Gronoff, Guillaume, et al.
(författare)
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The Effect of Cosmic Rays on Cometary Nuclei. I. Dose Deposition
- 2020
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Ingår i: Astrophysical Journal. - : Institute of Physics (IOP). - 0004-637X .- 1538-4357. ; 890:1
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Tidskriftsartikel (refereegranskat)abstract
- Comets are small bodies thought to contain the most pristine material in the solar system. However, since their formation ≈4.5 Gy ago, they have been altered by different processes. While not exposed to much electromagnetic radiation, they experience intense particle radiation. Galactic cosmic rays and solar energetic particles have a broad spectrum of energies and interact with the cometary surface and subsurface; they are the main source of space weathering for a comet in the Kuiper Belt or in the Oort Cloud, and also affect the ice prior to the comet agglomeration. While low-energy particles interact only with the cometary surface, the most energetic ones deposit a significant amount of energy down to tens of meters. This interaction can modify the isotopic ratios in cometary ices and create secondary compounds through radiolysis, such as O2 and H2O2 (Paper II). In this paper, we model the energy deposition of energetic particles as a function of depth using a Geant4 application modified to account for the isotope creation process. We quantify the energy deposited in cometary nucleus by galactic cosmic rays and solar energetic particles. The consequences of the energy deposition on the isotopic and chemical composition of cometary ices and their implication on the interpretation of cometary observations, notably of 67P/Churyumov Gerasimenko by the ESA Rosetta spacecraft, will be discussed in Paper II.
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| 35. |
- Gülk, Birte, 1994, et al.
(författare)
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Impacts of Vertical Convective Mixing Schemes and Freshwater Forcing on the 2016-2017 Maud Rise Polynya Openings in a Regional Ocean Simulation
- 2024
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Ingår i: JOURNAL OF ADVANCES IN MODELING EARTH SYSTEMS. - 1942-2466. ; 16:5
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Tidskriftsartikel (refereegranskat)abstract
- The correct representation of the Maud Rise open-ocean polynya in the Weddell Sea remains a challenge for ocean models. Here we reproduce the most recent polynya openings in 2016-2017 using a regional configuration, and assess their dependencies on vertical convective mixing schemes and freshwater forcing, both separately and in combination. We test three vertical convective mixing schemes: the enhanced vertical diffusion (EVD), the Eddy-Diffusivity Mass-Flux (EDMF) parameterization, and a modified version of EDMF accounting for thermobaric effects. Using simulations for the period 2007-2017, we find that the modified EDMF reproduces the observed climatological evolution of the mixed layer depth better than the original EDMF and the EVD, but a polynya fails to open due to excessive freshwater forcing. We thus use the modified EDMF to perform sensitivity experiments with reduced precipitation during 2012-2017. The imposed freshwater forcing strongly affects the number of years with polynyas. The simulation with the best representation of the 2016-2017 polynyas is analyzed to evaluate the triggering mechanisms. The 2016 polynya was induced by the action of thermobaric instabilities on a weak ambient stratification. This opening preconditioned the water column for 2017, which produced a stronger polynya. By examining the impacts of the different convective mixing schemes, we show that the modified EDMF generates more realistic patterns of deep convection. Our results highlight the importance of surface freshwater forcing and thermobaricity in governing deep convection around Maud Rise, and the need to represent thermobaric instabilities to realistically model Maud Rise polynyas. We investigate the impacts of representing numerical vertical mixing and surface freshwater forcing in a regional ocean model on polynyas (large openings in the pack ice) at Maud Rise, Southern Ocean. Maud Rise is prone to hosting polynyas, often associated with deep convection, which is a local vertical mixing process homogenizing the water column between surface and depths of several hundred meters. Numerical models often use simplistic strategies to represent this process, but improved parameterizations have recently become available. In this work, we test the impact of the representation of convective mixing in a particularly sensitive region. The last Maud Rise polynyas were observed in 2016 and 2017. Our regional simulation is capable of reproducing these polynyas, which has long been a challenge for ocean-sea ice models. We show that the 2016 polynya resulted from the action of a vertical instability at depth acting on weak ambient stratification. This event preconditioned the stronger 2017 polynya and deep convection. We conclude that representing convective plumes as a sub-grid scale process in models leads to a more realistic representation of open-ocean polynyas and associated convection events. The Eddy-Diffusivity Mass-Flux (EDMF) parameterization is tested in a regional simulation of the ocean around Maud Rise Thermobaric effects on convective plumes are enabled by modifying the EDMF parameterization Simulations of Maud Rise polynyas are highly sensitive to freshwater forcing and mixing schemes
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| 36. |
- Gupta, G., et al.
(författare)
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Exploiting Mass Spectrometry to Unlock the Mechanism of Nanoparticle-Induced Inflammasome Activation
- 2023
-
Ingår i: Acs Nano. - : AMER CHEMICAL SOC. - 1936-0851 .- 1936-086X. ; 17:17, s. 17451-17467
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Tidskriftsartikel (refereegranskat)abstract
- Nanoparticles (NPs) elicit sterile inflammation, but the underlying signaling pathways are poorly understood. Here, we report that human monocytes are particularly vulnerable to amorphous silica NPs, as evidenced by single-cell-based analysis of peripheral blood mononuclear cells using cytometry by time-of-flight (CyToF), while silane modification of the NPs mitigated their toxicity. Using human THP-1 cells as a model, we observed cellular internalization of silica NPs by nanoscale secondary ion mass spectrometry (nanoSIMS) and this was confirmed by transmission electron microscopy. Lipid droplet accumulation was also noted in the exposed cells. Furthermore, time-of-flight secondary ion mass spectrometry (ToF-SIMS) revealed specific changes in plasma membrane lipids, including phosphatidylcholine (PC) in silica NP-exposed cells, and subsequent studies suggested that lysophosphatidylcholine (LPC) acts as a cell autonomous signal for inflammasome activation in the absence of priming with a microbial ligand. Moreover, we found that silica NPs elicited NLRP3 inflammasome activation in monocytes, whereas cell death transpired through a non-apoptotic, lipid peroxidation-dependent mechanism. Together, these data further our understanding of the mechanism of sterile inflammation.
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| 37. |
- Jakobsson, Martin, et al.
(författare)
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The International Bathymetric Chart of the Arctic Ocean Version 4.0
- 2020
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Bathymetry (seafloor depth), is a critical parameter providing the geospatial context for a multitude of marine scientific studies. Since 1997, the International Bathymetric Chart of the Arctic Ocean (IBCAO) has been the authoritative source of bathymetry for the Arctic Ocean. IBCAO has merged its efforts with the Nippon Foundation-GEBCO-Seabed 2030 Project, with the goal of mapping all of the oceans by 2030. Here we present the latest version (IBCAO Ver. 4.0), with more than twice the resolution (200 x 200m versus 500 x 500m) and with individual depth soundings constraining three times more area of the Arctic Ocean (similar to 19.8% versus 6.7%), than the previous IBCAO Ver. 3.0 released in 2012. Modern multibeam bathymetry comprises similar to 14.3% in Ver. 4.0 compared to similar to 5.4% in Ver. 3.0. Thus, the new IBCAO Ver. 4.0 has substantially more seafloor morphological information that offers new insights into a range of submarine features and processes; for example, the improved portrayal of Greenland fjords better serves predictive modelling of the fate of the Greenland Ice Sheet. Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.12369314
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| 38. |
- Kliemann, Nathalie, et al.
(författare)
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Metabolically Defined Body Size Phenotypes and Risk of Endometrial Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)
- 2022
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : NLM. - 1055-9965 .- 1538-7755. ; 31:7, s. 1359-1367
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Obesity is a risk factor for endometrial cancer but whether metabolic dysfunction is associated with endometrial cancer independent of body size is not known.METHODS: The association of metabolically defined body size phenotypes with endometrial cancer risk was investigated in a nested case-control study (817 cases/ 817 controls) within the European Prospective Investigation into Cancer and Nutrition (EPIC). Concentrations of C-peptide were used to define metabolically healthy (MH; <1st tertile) and metabolically unhealthy (MU; ≥1st tertile) status among the control participants. These metabolic health definitions were combined with normal weight (NW); body mass index (BMI)<25 kg/m2 or waist circumference (WC)<80 cm or waist-to-hip ratio (WHR)<0.8) and overweight (OW; BMI≥25 kg/m2 or WC≥80 cm or WHR≥0.8) status, generating four phenotype groups for each anthropometric measure: (i) MH/NW, (ii) MH/OW, (iii) MU/NW, and (iv) MU/OW.RESULTS: In a multivariable-adjusted conditional logistic regression model, compared with MH/NW individuals, endometrial cancer risk was higher among those classified as MU/NW [ORWC, 1.48; 95% confidence interval (CI), 1.05-2.10 and ORWHR, 1.68; 95% CI, 1.21-2.35] and MU/OW (ORBMI, 2.38; 95% CI, 1.73-3.27; ORWC, 2.69; 95% CI, 1.92-3.77 and ORWHR, 1.83; 95% CI, 1.32-2.54). MH/OW individuals were also at increased endometrial cancer risk compared with MH/NW individuals (ORWC, 1.94; 95% CI, 1.24-3.04).CONCLUSIONS: Women with metabolic dysfunction appear to have higher risk of endometrial cancer regardless of their body size. However, OW status raises endometrial cancer risk even among women with lower insulin levels, suggesting that obesity-related pathways are relevant for the development of this cancer beyond insulin.IMPACT: Classifying women by metabolic health may be of greater utility in identifying those at higher risk for endometrial cancer than anthropometry per se.
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| 39. |
- Lehikoinen, Aleksi, et al.
(författare)
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Wintering bird communities are tracking climate change faster than breeding communities
- 2021
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Ingår i: Journal of Animal Ecology. - : Wiley. - 0021-8790 .- 1365-2656. ; 90:5, s. 1085-1095
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Tidskriftsartikel (refereegranskat)abstract
- Global climate change is driving species' distributions towards the poles and mountain tops during both non-breeding and breeding seasons, leading to changes in the composition of natural communities. However, the degree of season differences in climate-driven community shifts has not been thoroughly investigated at large spatial scales. We compared the rates of change in the community composition during both winter (non-breeding season) and summer (breeding) and their relation to temperature changes. Based on continental-scale data from Europe and North America, we examined changes in bird community composition using the community temperature index (CTI) approach and compared the changes with observed regional temperature changes during 1980–2016. CTI increased faster in winter than in summer. This seasonal discrepancy is probably because individuals are less site-faithful in winter, and can more readily shift their wintering sites in response to weather in comparison to the breeding season. Regional long-term changes in community composition were positively associated with regional temperature changes during both seasons, but the pattern was only significant during summer due to high annual variability in winter communities. Annual changes in community composition were positively associated with the annual temperature changes during both seasons. Our results were broadly consistent across continents, suggesting some climate-driven restructuring in both European and North American avian communities. Because community composition has changed much faster during the winter than during the breeding season, it is important to increase our knowledge about climate-driven impacts during the less-studied non-breeding season.
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| 40. |
- Perrot, Nicolas, et al.
(författare)
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Genetic and In Vitro Inhibition of PCSK9 and Calcific Aortic Valve Stenosis
- 2020
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Ingår i: JACC: Basic to Translational Science. - : Elsevier BV. - 2452-302X. ; 5:7, s. 649-661
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Tidskriftsartikel (refereegranskat)abstract
- The authors investigated whether PCSK9 inhibition could represent a therapeutic strategy in calcific aortic valve stenosis (CAVS). A meta-analysis of 10 studies was performed to determine the impact of the PCSK9 R46L variant on CAVS, and the authors found that CAVS was less prevalent in carriers of this variant (odds ratio: 0.80 [95% confidence interval: 0.70 to 0.91]; p = 0.0011) compared with noncarriers. PCSK9 expression was higher in the aortic valves of patients CAVS compared with control patients. In human valve interstitials cells submitted to a pro-osteogenic medium, PCSK9 levels increased and a PCSK9 neutralizing antibody significantly reduced calcium accumulation.
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| 41. |
- Perrot, Nicolas, et al.
(författare)
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Lipoprotein-associated phospholipase A2 activity, genetics and calcific aortic valve stenosis in humans
- 2020
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Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 106:18, s. 1407-1412
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Lipoprotein-associated phospholipase A2 (Lp-PLA2) activity has been shown to predict calcific aortic valve stenosis (CAVS) outcomes. Our objective was to test the association between plasma Lp-PLA2 activity and genetically elevated Lp-PLA2 mass/activity with CAVS in humans. Methods and results: Lp-PLA2 activity was measured in 890 patients undergoing cardiac surgery, including 476 patients undergoing aortic valve replacement for CAVS and 414 control patients undergoing coronary artery bypass grafting. After multivariable adjustment, Lp-PLA2 activity was positively associated with the presence of CAVS (OR=1.21 (95% CI 1.04 to 1.41) per SD increment). We selected four single nucleotide polymorphisms (SNPs) at the PLA2G7 locus associated with either Lp-PLA2 mass or activity (rs7756935, rs1421368, rs1805017 and rs4498351). Genetic association studies were performed in eight cohorts: Quebec-CAVS (1009 cases/1017 controls), UK Biobank (1350 cases/349 043 controls), European Prospective Investigation into Cancer and Nutrition-Norfolk (504 cases/20 307 controls), Genetic Epidemiology Research on Aging (3469 cases/51 723 controls), Malmö Diet and Cancer Study (682 cases/5963 controls) and three French cohorts (3123 cases/6532 controls), totalling 10 137 CAVS cases and 434 585 controls. A fixed-effect meta-analysis using the inverse-variance weighted method revealed that none of the four SNPs was associated with CAVS (OR=0.99 (95% CI 0.96 to 1.02, p=0.55) for rs7756935, 0.97 (95% CI 0.93 to 1.01, p=0.11) for rs1421368, 1.00 (95% CI 1.00 to 1.01, p=0.29) for rs1805017, and 1.00 (95% CI 0.97 to 1.04, p=0.87) for rs4498351). Conclusions: Higher Lp-PLA2 activity is significantly associated with the presence of CAVS and might represent a biomarker of CAVS in patients with heart disease. Results of our genetic association study suggest that Lp-PLA2 is however unlikely to represent a causal risk factor or therapeutic target for CAVS.
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| 42. |
- Reuter, Fabian, et al.
(författare)
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Laser-induced, single droplet fragmentation dynamics revealed through megahertz x-ray microscopy
- 2023
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Ingår i: Physics of Fluids. - 1070-6631. ; 35:11
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Tidskriftsartikel (refereegranskat)abstract
- The fragmentation dynamics of single water droplets from laser irradiation is studied with megahertz frame rate x-ray microscopy. Owed to the nearly refraction-free and penetrating imaging technique, we could look into the interior of the droplet and reveal that two mechanisms are responsible for the initial explosive fragmentation of the droplet. First, reflection and diffraction of the laser beam at the droplet interface result in the formation of laser ray caustics that lead to non-homogeneous heating of the droplet, locally above the critical temperature. Second, homogeneous cavitation in the droplet that is likely caused from shockwaves reflected as tension waves at the acoustic soft boundaries of the droplet. Further atomization occurs in three stages, first a fine sub-micrometer sized mist forms on the side of the droplet posterior to laser incidence, then micrometer sized droplets are expelled from the rim of an expanding liquid sheet, and finally into droplets of larger size through hole and ligament formation in the thinning liquid sheet where ligaments pinch off.
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| 43. |
- Rochman, Dimitri, et al.
(författare)
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The TENDL library : Hope, reality and future
- 2017
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Ingår i: Nd 2016 Bruges. - Les Ulis : EDP Sciences. - 9782759890200
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Konferensbidrag (refereegranskat)abstract
- The TALYS Evaluated Nuclear Data Library (TENDL) has now 8 releases since 2008. Considerable experience has been acquired for the production of such general-purpose nuclear data library based on the feedback from users, evaluators and processing experts. The backbone of this achievement is simple and robust: completeness, quality and reproducibility. If TENDL is extensively used in many fields of applications, it is necessary to understand its strong points and remaining weaknesses. Alternatively, the essential knowledge is not the TENDL library itself, but rather the necessary method and tools, making the library a side product and focusing the efforts on the evaluation knowledge. The future of such approach will be discussed with the hope of nearby greater success.
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| 44. |
- Santos, Alan C., et al.
(författare)
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Generating long-lived entangled states with free-space collective spontaneous emission
- 2022
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Ingår i: Physical Review A: covering atomic, molecular, and optical physics and quantum information. - 2469-9926 .- 2469-9934. ; 105:5
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Tidskriftsartikel (refereegranskat)abstract
- Considering the paradigmatic case of a cloud of two-level atoms interacting through common vacuum modes, we show how cooperative spontaneous emission, which is at the origin of superradiance, leads the system to long-lived entangled states at late times. These subradiant modes are characterized by an entanglement between all particles, independently of their geometrical configuration. While there is no threshold on the interaction strength necessary to entangle all particles, stronger interactions lead to longer-lived entanglement.
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| 45. |
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| 46. |
- Soyama, Hitoshi, et al.
(författare)
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Revealing the origins of vortex cavitation in a Venturi tube by high speed X-ray imaging
- 2023
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Ingår i: Ultrasonics Sonochemistry. - 1350-4177. ; 101
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Tidskriftsartikel (refereegranskat)abstract
- Hydrodynamic cavitation is useful in many processing applications, for example, in chemical reactors, water treatment and biochemical engineering. An important type of hydrodynamic cavitation that occurs in a Venturi tube is vortex cavitation known to cause luminescence whose intensity is closely related to the size and number of cavitation events. However, the mechanistic origins of bubbles constituting vortex cavitation remains unclear, although it has been concluded that the pressure fields generated by the cavitation collapse strongly depends on the bubble geometry. The common view is that vortex cavitation consists of numerous small spherical bubbles. In the present paper, aspects of vortex cavitation arising in a Venturi tube were visualized using high-speed X-ray imaging at SPring-8 and European XFEL. It was discovered that vortex cavitation in a Venturi tube consisted of angulated rather than spherical bubbles. The tangential velocity of the surface of vortex cavitation was assessed considering the Rankine vortex model.
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| 47. |
- van Dijk, Joanke, et al.
(författare)
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Managing PMT/vPvM substances in consumer products through the concepts of essential-use and functional substitution : a case-study for cosmetics
- 2023
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Ingår i: Environmental Science. - 2050-7887 .- 2050-7895. ; 25:6, s. 1067-1081
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Tidskriftsartikel (refereegranskat)abstract
- Measures are needed to protect water sources from substances that are mobile, persistent and toxic (PMT) or very persistent and very mobile (vPvM). PMT/vPvM substances are used in a diverse range of applications, including consumer products. The combined application of the essential-use and functional substitution concepts has been proposed to phase out substances of concern and support the transition to safer and more sustainable chemicals, a key goal of the European Commission’s Chemicals Strategy for Sustainability. Here, we first identified the market share of PMT/vPvM containing cosmetic products. We found that 6.4% of cosmetic products available on the European market contain PMT or vPvM substances. PMT/vPvM substances were most often found in hair care products. Based on their high occurrence, the substances Allura red (CAS 25956-17-6), benzophenone-4 (CAS 4065-45-6) and climbazole (CAS 38083-17-9) were selected as case-studies for assessment of their functionality, availability of safer alternatives and essentiality. Following the functional substitution framework, we found that the technical function of Allura red was not necessary for the performance of some cosmetic products, making the use non-essential. For other applications of Allura red, as well as all applications of benzophenone-4 and climbazole, the technical function of the chemical was considered necessary for the performance. Via the alternative’s assessment procedure, which used experimental and in silico data and three different multicriteria decision analysis (MCDA) strategies, safer alternatives were identified for all case-study chemicals. All assessed uses of PMT/vPvM substances were thus deemed non-essential and should consequently be phased out.
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| 48. |
- Villanueva Perez, Pablo, et al.
(författare)
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Megahertz X-ray Multi-projection imaging
- 2023
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Ingår i: arXiv.org. - 2331-8422.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- X-ray time-resolved tomography is one of the most popular X-raytechniques to probe dynamics in three dimensions (3D). Recent developments in time-resolved tomography opened the possibility of recordingkilohertz-rate 3D movies. However, tomography requires rotating thesample with respect to the X-ray beam, which prevents characterization of faster structural dynamics. Here, we present megahertz (MHz)X-ray multi-projection imaging (MHz-XMPI), a technique capable ofrecording volumetric information at MHz rates and micrometer resolution without scanning the sample. We achieved this by harnessing theunique megahertz pulse structure and intensity of the European X-rayFree-electron Laser with a combination of novel detection and reconstruction approaches that do not require sample rotations. Our approachenables generating multiple X-ray probes that simultaneously record several angular projections for each pulse in the megahertz pulse burst.We provide a proof-of-concept demonstration of the MHz-XMPI technique’s capability to probe 4D (3D+time) information on stochasticphenomena and non-reproducible processes three orders of magnitudefaster than state-of-the-art time-resolved X-ray tomography, by generating 3D movies of binary droplet collisions. We anticipate that MHz-XMPIwill enable in-situ and operando studies that were impossible before,either due to the lack of temporal resolution or because the systemswere opaque (such as for MHz imaging based on optical microscopy).
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| 49. |
- Zhuang, Yulong, et al.
(författare)
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Unsupervised learning approaches to characterizing heterogeneous samples using X-ray single-particle imaging
- 2022
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Ingår i: IUCrJ. - : International Union of Crystallography (IUCr). - 2052-2525. ; 9, s. 204-214
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Tidskriftsartikel (refereegranskat)abstract
- One of the outstanding analytical problems in X-ray single-particle imaging (SPI) is the classification of structural heterogeneity, which is especially difficult given the low signal-to-noise ratios of individual patterns and the fact that even identical objects can yield patterns that vary greatly when orientation is taken into consideration. Proposed here are two methods which explicitly account for this orientation-induced variation and can robustly determine the structural landscape of a sample ensemble. The first, termed common-line principal component analysis (PCA), provides a rough classification which is essentially parameter free and can be run automatically on any SPI dataset. The second method, utilizing variation auto-encoders (VAEs), can generate 3D structures of the objects at any point in the structural landscape. Both these methods are implemented in combination with the noise-tolerant expand-maximizecompress (EMC) algorithm and its utility is demonstrated by applying it to an experimental dataset from gold nanoparticles with only a few thousand photons per pattern. Both discrete structural classes and continuous deformations are recovered. These developments diverge from previous approaches of extracting reproducible subsets of patterns from a dataset and open up the possibility of moving beyond the study of homogeneous sample sets to addressing open questions on topics such as nanocrystal growth and dynamics, as well as phase transitions which have not been externally triggered.
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