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| 2. |
- Rajewsky, N., et al.
(author)
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LifeTime and improving European healthcare through cell-based interceptive medicine
- 2020
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In: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 587:7834, s. 377-386
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Journal article (peer-reviewed)abstract
- LifeTime aims to track, understand and target human cells during the onset and progression of complex diseases and their response to therapy at single-cell resolution. This mission will be implemented through the development and integration of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during progression from health to disease. Analysis of such large molecular and clinical datasets will discover molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. Timely detection and interception of disease embedded in an ethical and patient-centered vision will be achieved through interactions across academia, hospitals, patient-associations, health data management systems and industry. Applying this strategy to key medical challenges in cancer, neurological, infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.
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| 3. |
- van Bragt, JJMH, et al.
(author)
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Characteristics and treatment regimens across ERS SHARP severe asthma registries
- 2020
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In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 55:1
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Journal article (peer-reviewed)abstract
- Little is known about the characteristics and treatments of patients with severe asthma across Europe, but both are likely to vary. This is the first study in the European Respiratory Society Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) Clinical Research Collaboration and it is designed to explore these variations. Therefore, we aimed to compare characteristics of patients in European severe asthma registries and treatments before starting biologicals.This was a cross-sectional retrospective analysis of aggregated data from 11 national severe asthma registries that joined SHARP with established patient databases.Analysis of data from 3236 patients showed many differences in characteristics and lifestyle factors. Current smokers ranged from 0% (Poland and Sweden) to 9.5% (Belgium), mean body mass index ranged from 26.2 (Italy) to 30.6 kg·m−2 (the UK) and the largest difference in mean pre-bronchodilator forced expiratory volume in 1 s % predicted was 20.9% (the Netherlands versus Hungary). Before starting biologicals patients were treated differently between countries: mean inhaled corticosteroid dose ranged from 700 to 1335 µg·day−1 between those from Slovenia versus Poland when starting anti-interleukin (IL)-5 antibody and from 772 to 1344 µg·day−1 in those starting anti-IgE (Slovenia versus Spain). Maintenance oral corticosteroid use ranged from 21.0% (Belgium) to 63.0% (Sweden) and from 9.1% (Denmark) to 56.1% (the UK) in patients starting anti-IL-5 and anti-IgE, respectively.The severe asthmatic population in Europe is heterogeneous and differs in both clinical characteristics and treatment, often appearing not to comply with the current European Respiratory Society/American Thoracic Society guidelines definition of severe asthma. Treatment regimens before starting biologicals were different from inclusion criteria in clinical trials and varied between countries.
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| 4. |
- de Fouw, Jimmy, et al.
(author)
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A facultative mutualism facilitates European seagrass meadows
- 2023
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In: Ecography. - 0906-7590 .- 1600-0587. ; 2023:5
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Journal article (peer-reviewed)abstract
- Coastal ecosystem functioning often hinges on habitat-forming foundation species that engage in positive interactions (e.g. facilitation and mutualism) to reduce environmental stress. Seagrasses are important foundation species in coastal zones but are rapidly declining with losses typically linked to intensifying global change-related environmental stress. There is growing evidence that loss or disruption of positive interactions can amplify coastal ecosystem degradation as it compromises its stress mitigating capacity. Multiple recent studies highlight that seagrass can engage in a facultative mutualistic relationship with lucinid bivalves that alleviate sulphide toxicity. So far, however, the generality of this mutualism, and how its strength and relative importance depend on environmental conditions, remains to be investigated. Here we study the importance of the seagrass-lucinid mutualistic interaction on a continental-scale using a field survey across Europe. We found that the lucinid bivalve Loripes orbiculatus is associated with the seagrasses Zostera noltii and Zostera marina across a large latitudinal range. At locations where the average minimum temperature was above 1 °C, L. orbiculatus was present in 79% of the Zostera meadows; whereas, it was absent below this temperature. At locations above this minimum temperature threshold, mud content was the second most important determinant explaining the presence or absence of L. orbiculatus. Further analyses suggest that the presence of the lucinids have a positive effect on seagrass biomass by mitigating sulphide stress. Finally, results of a structural equation model (SEM) support the existence of a mutualistic feedback between L. orbiculatus and Z. noltii. We argue that this seagrass-lucinid mutualism should be more solidly integrated into management practices to improve seagrass ecosystem resilience to global change as well as the success of restoration efforts.
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| 6. |
- van de Ven, Hardy A, et al.
(author)
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Associations between shift schedule characteristics with sleep, need for recovery, health and performance measures for regular (semi-)continuous 3-shift systems.
- 2016
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In: Applied Ergonomics. - : Elsevier BV. - 0003-6870 .- 1872-9126. ; 56, s. 203-212
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Journal article (peer-reviewed)abstract
- In this cross-sectional study associations were examined between eight shift schedule characteristics with shift-specific sleep complaints and need for recovery and generic health and performance measures. It was hypothesized that shift schedule characteristics meeting ergonomic recommendations are associated with better sleep, need for recovery, health and performance. Questionnaire data were collected from 491 shift workers of 18 companies with 9 regular (semi)-continuous shift schedules. The shift schedule characteristics were analyzed separately and combined using multilevel linear regression models. The hypothesis was largely not confirmed. Relatively few associations were found, of which the majority was in the direction as expected. In particular early starts of morning shifts and many consecutive shifts seem to be avoided. The healthy worker effect, limited variation between included schedules and the cross-sectional design might explain the paucity of significant results.
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| 8. |
- Eekers, Danielle B. P., et al.
(author)
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The EPTN consensus-based atlas for CT- and MR-based contouring in neuro-oncology
- 2018
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In: Radiotherapy and Oncology. - : ELSEVIER IRELAND LTD. - 0167-8140 .- 1879-0887. ; 128:1, s. 37-43
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Journal article (peer-reviewed)abstract
- Purpose: To create a digital, online atlas for organs at risk (OAR) delineation in neuro-oncology based on high-quality computed tomography (Cr) and magnetic resonance (MR) imaging. Methods: CT and 3 Tesla (3T) MR images (slice thickness 1 mm with intravenous contrast agent) were obtained from the same patient and subsequently fused. In addition, a 7T MR without intravenous contrast agent was obtained from a healthy volunteer. Based on discussion between experienced radiation oncologists, the clinically relevant organs at risk (OARs) to be included in the atlas for neuro-oncology were determined, excluding typical head and neck OARs previously published. The draft atlas was delineated by a senior radiation oncologist, 2 residents in radiation oncology, and a senior neuro-radiologist incorporating relevant available literature. The proposed atlas was then critically reviewed and discussed by European radiation oncologists until consensus was reached. Results: The online atlas includes one CT-scan at two different window settings and one MR scan (3T) showing the OARs in axial, coronal and sagittal view. This manuscript presents the three-dimensional descriptions of the fifteen consensus OARs for neuro-oncology. Among these is a new OAR relevant for neuro-cognition, the posterior cerebellum (illustrated on 7T MR images). Conclusion: In order to decrease inter- and intra-observer variability in delineating OARs relevant for neuro-oncology and thus derive consistent dosimetric data, we propose this atlas to be used in photon and particle therapy. The atlas is available online at w.cancerdata.c and will be updated whenever required.
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| 9. |
- Lilienthal, Hellmuth, et al.
(author)
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Auditory effects of developmental exposure to purity-controlled Polychlorinated Biphenyls (PCB52 and PCB180) in rats
- 2011
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In: Toxicological Sciences. - : Oxford Journals. - 1096-6080 .- 1096-0929. ; 122:1, s. 100-111
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Journal article (peer-reviewed)abstract
- Polychlorinated biphenyls (PCBs) are still present in the environment, with ongoing exposure in humans, including babies nursed by their mothers. Whereas toxicity of dioxin-like PCBs is well described, less systematic knowledge is available for non-dioxin-like PCBs (NDL-PCBs) which do not act via the Ah receptor. This study compared effects of developmental exposure to two ultrapure NDL-PCB congeners (PCB52 and PCB180) on auditory function in rats, using the brainstem auditory evoked potential (BAEP). Pregnant rats received repeated oral doses of PCB52 (total dose - 0, 30, 100, 300, 1000, or 3000 mg/kg body weight) or of PCB180 (total dose - 0, 10, 30, 100, 300, or 1000 mg/kg). BAEPs were recorded in adult male and female offspring after stimulation with clicks or pure tones in the frequency range from 0.5 kHz to 16 kHz. Significant elevation of BAEP thresholds were detected in the low-frequency range after developmental exposure to PCB52. Calculation of benchmark doses revealed lowest values in the frequency range of 0.5 - 2 kHz. Effects were more pronounced in male compared to female offspring. Latencies of waves II and IV were prolonged in exposed males, while only wave IV was affected in females. PCB180 increased thresholds only at few conditions and only in female offspring. These results confirm that developmental exposure to ultrapure NDL-PCBs affects auditory function, but different congeners exhibit differences in potencies.
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| 10. |
- Lilienthal, Hellmuth, et al.
(author)
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Dopamine-dependent behavior in adult rats after perinatal exposure to purity-controlled polychlorinated biphenyl congeners (PCB52 and PCB180)
- 2014
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In: Toxicology Letters. - : Elsevier. - 0378-4274 .- 1879-3169. ; 224:1, s. 32-39
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Journal article (peer-reviewed)abstract
- Since knowledge about toxic effects of non-dioxinlike (NDL) PCBs is fragmentary, regulatory panels have concluded that risk assessment of these congeners is hampered or impossible. As the dopaminergic system is one of the main targets in PCB-related neurotoxic effects after developmental exposure, we selected catalepsy induced by the dopamine receptor blocker haloperidol to characterize effects of the NDL congeners PCB52 and PCB180 in adult offspring from exposed rat dams. Rat dams were treated with PCB congeners by gavage using six dose levels (total doses: PCB52 - 0, 30, 100, 300, 1000 or 3000 mg/kg body wt.; PCB180 - 0, 10, 30, 100, 300, or 1000 mg/kg body wt.) to allow benchmark dose analysis of the results. Testing of adult offspring (starting at 180 days of age) for catalepsy induced by injection with haloperidol revealed slightly prolonged latencies to movement onset in female offspring exposed to PCB52. Exposure to PCB180 resulted in more pronounced effects, with generally reduced latencies in male offspring. These results indicate reduced dopaminergic activity after PCB52 exposure, whereas the outcome for PCB180 may be related to increased extracellular dopamine as reported in the literature. Benchmark dose analyses revealed that both PCB congeners exerted effects mainly at moderate exposure levels. Together, these results underline the importance of effects on the dopaminergic system as indicated by studies in human females after occupational PCB exposure.
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