| 1. |
- Li, Constance H., et al.
(author)
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Sex differences in oncogenic mutational processes
- 2020
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11
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Journal article (peer-reviewed)abstract
- Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.
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| 2. |
- Sánchez-Cano, Beatriz, et al.
(author)
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Solar Energetic Particle Events Detected in the Housekeeping Data of the European Space Agency's Spacecraft Flotilla in the Solar System
- 2023
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In: Space Weather. - : American Geophysical Union (AGU). - 1542-7390. ; 21:8
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Journal article (peer-reviewed)abstract
- Despite the growing importance of planetary Space Weather forecasting and radiation protection for science and robotic exploration and the need for accurate Space Weather monitoring and predictions, only a limited number of spacecraft have dedicated instrumentation for this purpose. However, every spacecraft (planetary or astronomical) has hundreds of housekeeping sensors distributed across the spacecraft, some of which can be useful to detect radiation hazards produced by solar particle events. In particular, energetic particles that impact detectors and subsystems on a spacecraft can be identified by certain housekeeping sensors, such as the Error Detection and Correction (EDAC) memory counters, and their effects can be assessed. These counters typically have a sudden large increase in a short time in their error counts that generally match the arrival of energetic particles to the spacecraft. We investigate these engineering datasets for scientific purposes and perform a feasibility study of solar energetic particle event detections using EDAC counters from seven European Space Agency Solar System missions: Venus Express, Mars Express, ExoMars-Trace Gas Orbiter, Rosetta, BepiColombo, Solar Orbiter, and Gaia. Six cases studies, in which the same event was observed by different missions at different locations in the inner Solar System are analyzed. The results of this study show how engineering sensors, for example, EDAC counters, can be used to infer information about the solar particle environment at each spacecraft location. Therefore, we demonstrate the potential of the various EDAC to provide a network of solar particle detections at locations where no scientific observations of this kind are available.
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| 3. |
- Achten, Peter, et al.
(author)
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MEASURING THE LOSSES OF HYDROSTATIC PUMPS AND MOTORS: A CRITICAL REVIEW OF ISO4409:2007
- 2020
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In: PROCEEDINGS OF THE ASME/BATH SYMPOSIUM ON FLUID POWER AND MOTION CONTROL, 2019. - : AMER SOC MECHANICAL ENGINEERS. - 9780791859339
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Conference paper (peer-reviewed)abstract
- ISO 4409 is the most important international standard for measuring the efficiency of hydraulic pumps and motors, the latest edition being 4409:2007. The standard describes methods for determining the steady-state performance in terms of overall efficiency. It also defines equations for calculating the volumetric efficiency of pumps and motors. The hydromechanical efficiency is only defined for motors, not for pumps. This paper analyses the efficiency and losses of pumps and motors in an alternative way. The preference is on loss analysis instead of efficiencies. Especially the effects of the bulk modulus are considered in a different and more inclusive manner. The new methodology results in a higher total loss for motor and a lower total loss for pumps than the current ISO 4409 standard. Furthermore, it results in significant changes of the hydro-mechanical and volumetric losses. The differences between the new methodology and ISO 4409 become larger for high load pressures. The new methodology demands knowledge about the minimum volume of the displacement chamber. The ratio between this volume and the full displacement of a single displacement chamber strongly influences the hydro mechanical and volumetric losses of the pump or motor. The new methodology is valid for all positive displacement hydrostatic pumps and motors. The volumetric efficiency, as defined in ISO 4409, can still be used as a flow rate factor, but should not be regarded as an energy conversion efficiency. The importance of adopting the proposed methodology is further demonstrated by analyzing and comparing the measurement data about a fixed displacement pump and motor, showing the differences in the loss analysis by means of ISO 4409 and the new equations. The methodology, observations and validation results presented in this paper are significant and can pave the road for improving the current ISO 4409:2007 standard, which would ultimately benefit the industry.
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| 4. |
- Barucca, G., et al.
(author)
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The potential of Λ and Ξ- studies with PANDA at FAIR
- 2021
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In: European Physical Journal A. - : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:4
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Journal article (peer-reviewed)abstract
- The antiproton experiment PANDA at FAIR is designed to bring hadron physics to a new level in terms of scope, precision and accuracy. In this work, its unique capability for studies of hyperons is outlined. We discuss ground-state hyperons as diagnostic tools to study non-perturbative aspects of the strong interaction, and fundamental symmetries. New simulation studies have been carried out for two benchmark hyperon-antihyperon production channels: p¯ p→ Λ¯ Λ and p¯ p→ Ξ¯ +Ξ-. The results, presented in detail in this paper, show that hyperon-antihyperon pairs from these reactions can be exclusively reconstructed with high efficiency and very low background contamination. In addition, the polarisation and spin correlations have been studied, exploiting the weak, self-analysing decay of hyperons and antihyperons. Two independent approaches to the finite efficiency have been applied and evaluated: one standard multidimensional efficiency correction approach, and one efficiency independent approach. The applicability of the latter was thoroughly evaluated for all channels, beam momenta and observables. The standard method yields good results in all cases, and shows that spin observables can be studied with high precision and accuracy already in the first phase of data taking with PANDA.
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| 5. |
- Frykholm, Peter, 1961-, et al.
(author)
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Pre-operative fasting in children : A guideline from the European Society of Anaesthesiology and Intensive Care
- 2022
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In: European Journal of Anaesthesiology. - : European Society of Anaesthesiology and Intensive Care. - 0265-0215 .- 1365-2346. ; 39:1, s. 4-25
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Journal article (peer-reviewed)abstract
- Current paediatric anaesthetic fasting guidelines have recommended conservative fasting regimes for many years and have not altered much in the last decades. Recent publications have employed more liberal fasting regimes with no evidence of increased aspiration or regurgitation rates. In this first solely paediatric European Society of Anaesthesiology and Intensive Care (ESAIC) pre-operative fasting guideline, we aim to present aggregated and evidence-based summary recommendations to assist clinicians, healthcare providers, patients and parents.We identified six main topics for the literature search: studies comparing liberal with conservative regimens; impact of food composition; impact of comorbidity; the use of gastric ultrasound as a clinical tool; validation of gastric ultrasound for gastric content and gastric emptying studies; and early postoperative feeding. The literature search was performed by a professional librarian in collaboration with the ESAIC task force.Recommendations for reducing clear fluid fasting to 1 h, reducing breast milk fasting to 3 h, and allowing early postoperative feeding were the main results, with GRADE 1C or 1B evidence. The available evidence suggests that gastric ultrasound may be useful for clinical decision-making, and that allowing a ‘light breakfast’ may be well tolerated if the intake is well controlled. More research is needed in these areas as well as evaluation of how specific patient or treatment-related factors influence gastric emptying.
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| 6. |
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| 7. |
- Kranaster, Laura, et al.
(author)
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The novel seizure quality index for the antidepressant outcome prediction in electroconvulsive therapy: association with biomarkers in the cerebrospinal fluid.
- 2020
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In: European archives of psychiatry and clinical neuroscience. - : Springer Science and Business Media LLC. - 1433-8491 .- 0940-1334. ; 270:7, s. 911-919
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Journal article (peer-reviewed)abstract
- For patients with depression treated with electroconvulsive therapy (ECT), the novel seizure quality index (SQI) can predict the risk of non-response (and non-remission)-as early as after the second ECT session-based the extent of several ictal parameters of the seizure. We aim to test several CSF markers on their ability to predict the degree of seizure quality, measured by the SQI to identify possible factors, that could explain some variability of the seizure quality. Baseline CSF levels of metabolites from the kynurenine pathway, markers of neurodegeneration (tau proteins, β-amyloids and neurogranin), elements of the innate immune system, endocannabinoids, sphingolipids, neurotrophic factors (VEGF) and Klotho were measured before ECT in patients with depression (n=12) to identify possible correlations with the SQI by Pearson's partial correlation. Negative, linear relationships with the SQI for response were observed for CSF levels of T-tau (rpartial=-0.69, p=0.019), phosphatidylcholines (rpartial=-0.52, p=0.038) and IL-8 (rpartial=-0.67, p=0.047). Regarding the SQI for remission, a negative, linear relationship was noted with CSF levels of the endocannabinoid AEA (rpartial=-0.70, p=0.024) and CD163 (rpartial=-0.68, p=0.029). In sum, CSF Markers for the innate immune system, for neurodegeneration and from lipids were found to be associated with the SQI for response and remission after adjusting for age. Consistently, higher CSF levels of the markers were always associated with lower seizure quality. Based on these results, further research regarding the mechanism of seizure quality in ECT is suggested.
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| 8. |
- Llorens, Franc, et al.
(author)
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Cerebrospinal fluid lipocalin 2 as a novel biomarker for the differential diagnosis of vascular dementia
- 2020
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In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- The clinical diagnosis of vascular dementia (VaD) is based on imaging criteria, and specific biochemical markers are not available. Here, we investigated the potential of cerebrospinal fluid (CSF) lipocalin 2 (LCN2), a secreted glycoprotein that has been suggested as mediating neuronal damage in vascular brain injuries. The study included four independent cohorts with a total n=472 samples. LCN2 was significantly elevated in VaD compared to controls, Alzheimers disease (AD), other neurodegenerative dementias, and cognitively unimpaired patients with cerebrovascular disease. LCN2 discriminated VaD from AD without coexisting VaD with high accuracy. The main findings were consistent over all cohorts. Neuropathology disclosed a high percentage of macrophages linked to subacute infarcts, reactive astrocytes, and damaged blood vessels in multi-infarct dementia when compared to AD. We conclude that CSF LCN2 is a promising candidate biochemical marker in the differential diagnosis of VaD and neurodegenerative dementias. Diagnosis of vascular dementia is hampered by the lack of biochemical markers for this disease. Here, the authors show that vascular dementia is associated with increased lipocalin-2 in cerebrospinal fluid, compared to controls and patients with other forms of dementia.
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| 9. |
- Marchetto, Aldo, et al.
(author)
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Good Agreement Between Modeled and Measured Sulfur and Nitrogen Deposition in Europe, in Spite of Marked Differences in Some Sites
- 2021
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In: Frontiers in Environmental Science. - : Frontiers Media SA. - 2296-665X. ; 9
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Journal article (peer-reviewed)abstract
- Atmospheric nitrogen and sulfur deposition is an important effect of atmospheric pollution and may affect forest ecosystems positively, for example enhancing tree growth, or negatively, for example causing acidification, eutrophication, cation depletion in soil or nutritional imbalances in trees. To assess and design measures to reduce the negative impacts of deposition, a good estimate of the deposition amount is needed, either by direct measurement or by modeling. In order to evaluate the precision of both approaches and to identify possible improvements, we compared the deposition estimates obtained using an Eulerian model with the measurements performed by two large independent networks covering most of Europe. The results are in good agreement (bias <25%) for sulfate and nitrate open field deposition, while larger differences are more evident for ammonium deposition, likely due to the greater influence of local ammonia sources. Modeled sulfur total deposition compares well with throughfall deposition measured in forest plots, while the estimate of nitrogen deposition is affected by the tree canopy. The geographical distribution of pollutant deposition and of outlier sites where model and measurements show larger differences are discussed.
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| 10. |
- Schmitz, Alexander, et al.
(author)
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Longitudinal minimal residual disease assessment in multiple myeloma patients in complete remission : results from the NMSG flow-MRD substudy within the EMN02/HO95 MM trial
- 2022
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In: BMC Cancer. - : BMC. - 1471-2407. ; 22:1
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Journal article (peer-reviewed)abstract
- Background: Multiple myeloma remains an incurable disease with multiple relapses due to residual myeloma cells in the bone marrow of patients after therapy. Presence of small number of cancer cells in the body after cancer treatment, called minimal residual disease, has been shown to be prognostic for progression-free and overall survival. However, for multiple myeloma, it is unclear whether patients attaining minimal residual disease negativity may be candidates for treatment discontinuation. We investigated, if longitudinal flow cytometry-based monitoring of minimal residual disease (flow-MRD) may predict disease progression earlier and with higher sensitivity compared to biochemical assessments. Methods: Patients from the Nordic countries with newly diagnosed multiple myeloma enrolled in the European-Myeloma-Network-02/Hovon-95 (EMN02/HO95) trial and undergoing bone marrow aspiration confirmation of complete response, were eligible for this Nordic Myeloma Study Group (NMSG) substudy. Longitdudinal flow-MRD assessment of bone marrow samples was performed to identify and enumerate residual malignant plasma cells until observed clinical progression. Results: Minimal residual disease dynamics were compared to biochemically assessed changes in serum free light chain and M-component. Among 20 patients, reaching complete response or stringent complete response during the observation period, and with >= 3 sequential flow-MRD assessments analysed over time, increasing levels of minimal residual disease in the bone marrow were observed in six cases, preceding biochemically assessed disease and clinical progression by 5.5 months and 12.6 months (mean values), respectively. Mean malignant plasma cells doubling time for the six patients was 1.8 months (95% CI, 1.4-2.3 months). Minimal malignant plasma cells detection limit was 4 x 10-5. Conclusions: Flow-MRD is a sensitive method for longitudinal monitoring of minimal residual disease dynamics in multiple myeloma patients in complete response. Increasing minimal residual disease levels precedes biochemically assessed changes and is an early indicator of subsequent clinical progression.
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