| 1. |
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| 2. |
- Wilhelm, Matthias, et al.
(författare)
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Early Repolarization, Left Ventricular Diastolic Function, and Left Atrial Size in Professional Soccer Players
- 2010
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Ingår i: American Journal of Cardiology. - : Elsevier. - 0002-9149 .- 1879-1913. ; 106:4, s. 569-574
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Tidskriftsartikel (refereegranskat)abstract
- Recent data have suggested a relation among long-term endurance sport practice, left atrial remodeling, and atrial fibrillation. We investigated the influence of an increased vagal tone, represented by the early repolarization (ER) pattern, on diastolic function and left atrial size in professional soccer players. Fifty-four consecutive athletes underwent electrocardiography, echocardiography, and exercise testing as part of their preparticipation screening. Athletes were divided into 2 groups according to presence or absence of an ER pattern, defined as a ST-segment elevation at the J-point (STE) ≥0.1 mm in 2 leads. For linear comparisons average STE was calculated. Mean age was 24 ± 4 years. Twenty-five athletes (46%) showed an ER pattern. Athletes with an ER pattern had a significant lower heart rate (54 ± 9 vs 62 ± 11 beats/min, p = 0.024), an increased E/e′ ratio (6.1 ± 1.2 vs 5.1 ± 1.0, p = 0.002), and larger volumes of the left atrium (25.6 ± 7.3 vs 21.8 ± 5.0 ml/m2, p = 0.031) compared to athletes without an ER pattern. There were no significant differences concerning maximum workload, left ventricular dimensions, and systolic function. Univariate regression analysis revealed significant correlations among age, STE, and left atrial volume. In a stepwise multivariate regression analysis age, STE and e′ contributed independently to left atrial size (r = 0.659, p <0.001). In conclusion, athletes with an ER pattern had an increased E/e′ ratio, reflecting a higher left atrial filling pressure, contributing to left atrial remodeling over time.
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| 3. |
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| 4. |
- Aktaa, Suleman, et al.
(författare)
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European Society of Cardiology Quality Indicators for Cardiovascular Disease Prevention: developed by the Working Group for Cardiovascular Disease Prevention Quality Indicators in collaboration with the European Association for Preventive Cardiology of the European Society of Cardiology
- 2022
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Ingår i: European Journal of Preventive Cardiology. - : OXFORD UNIV PRESS. - 2047-4873 .- 2047-4881. ; 23:7, s. 1060-1071
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Tidskriftsartikel (refereegranskat)abstract
- Aims To develop a set of quality indicators (QIs) for the evaluation of the care and outcomes for atherosclerotic cardiovascular disease (ASCVD) prevention. Methods and results The Quality Indicator Committee of the European Society of Cardiology (ESC) formed the Working Group for Cardiovascular Disease Prevention Quality Indicators in collaboration with Task Force members of the 2021 ESC Guidelines on Cardiovascular Disease Prevention in Clinical Practice and the European Association of Preventive Cardiology (EAPC). We followed the ESC methodology for QI development, which involved (i) the identification of the key domains of care for ASCVD prevention by constructing a conceptual framework of care, (ii) the development of candidate QIs by conducting a systematic review of the literature, (iii) the selection of the final set of QIs using a modified Delphi method, and (iv) the evaluation of the feasibility of the developed QIs. In total, 17 main and 14 secondary QIs were selected across six domains of care for ASCVD prevention: (i) structural framework, (ii) risk assessment, (iii) care for people at risk for ASCVD, (iv) care for patients with established ASCVD, (v) patient education and experience, and (vi) outcomes. Conclusion We present the 2021 ESC QIs for Cardiovascular Disease Prevention, which have been co-constructed with EAPC using the ESC methodology for QI development. These indicators are supported by evidence from the literature, underpinned by expert consensus and aligned with the 2021 ESC Guidelines on Cardiovascular Disease Prevention in Clinical Practice to offer a mechanism for the evaluation of ASCVD prevention care and outcomes.
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| 7. |
- Giese, Holger, et al.
(författare)
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Towards the compositional verification of real-time UML designs
- 2003
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Ingår i: Proceedings of the 11th ACM SIGSOFT Symposium on Foundations of Software Engineering 2003 held jointly with 9th European Software Engineering Conference, ESEC/FSE 2003, Helsinki, Finland, September 1-5, 2003. ; , s. 38-47
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Konferensbidrag (refereegranskat)
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| 8. |
- Gröger, Matthias, et al.
(författare)
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Coupled regional Earth system modeling in the Baltic Sea region
- 2021
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Ingår i: Earth System Dynamics. - : Copernicus GmbH. - 2190-4979 .- 2190-4987. ; 12:3, s. 939-973
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Forskningsöversikt (refereegranskat)abstract
- Nonlinear responses to externally forced climate change are known to dampen or amplify the local climate impact due to complex cross-compartmental feedback loops in the Earth system. These feedbacks are less well represented in the traditional stand-alone atmosphere and ocean models on which many of today's regional climate assessments rely (e.g., EURO-CORDEX, NOSCCA and BACC II). This has promoted the development of regional climate models for the Baltic Sea region by coupling different compartments of the Earth system into more comprehensive models. Coupled models more realistically represent feedback loops than the information imposed on the region by prescribed boundary conditions and, thus, permit more degrees of freedom. In the past, several coupled model systems have been developed for Europe and the Baltic Sea region. This article reviews recent progress on model systems that allow two-way communication between atmosphere and ocean models; models for the land surface, including the terrestrial biosphere; and wave models at the air-sea interface and hydrology models for water cycle closure. However, several processes that have mostly been realized by one-way coupling to date, such as marine biogeochemistry, nutrient cycling and atmospheric chemistry (e.g., aerosols), are not considered here. In contrast to uncoupled stand-alone models, coupled Earth system models can modify mean near-surface air temperatures locally by up to several degrees compared with their stand-alone atmospheric counterparts using prescribed surface boundary conditions. The representation of small-scale oceanic processes, such as vertical mixing and sea-ice dynamics, appears essential to accurately resolve the air-sea heat exchange over the Baltic Sea, and these parameters can only be provided by online coupled high-resolution ocean models. In addition, the coupling of wave models at the ocean-atmosphere interface allows for a more explicit formulation of small-scale to microphysical processes with local feedbacks to water temperature and large-scale processes such as oceanic upwelling. Over land, important climate feedbacks arise from dynamical terrestrial vegetation changes as well as the implementation of land-use scenarios and afforestation/deforestation that further alter surface albedo, roughness length and evapotranspiration. Furthermore, a good representation of surface temperatures and roughness length over open sea and land areas is critical for the representation of climatic extremes such as heavy precipitation, storms, or tropical nights (defined as nights where the daily minimum temperature does not fall below 20gC), and these parameters appear to be sensitive to coupling. For the present-day climate, many coupled atmosphere-ocean and atmosphere-land surface models have demonstrated the added value of single climate variables, in particular when low-quality boundary data were used in the respective stand-alone model. This makes coupled models a prospective tool for downscaling climate change scenarios from global climate models because these models often have large biases on the regional scale. However, the coupling of hydrology models to close the water cycle remains problematic, as the accuracy of precipitation provided by atmosphere models is, in most cases, insufficient to realistically simulate the runoff to the Baltic Sea without bias adjustments. Many regional stand-alone ocean and atmosphere models are tuned to suitably represent present-day climatologies rather than to accurately simulate climate change. Therefore, more research is required into how the regional climate sensitivity (e.g., the models' response to a given change in global mean temperature) is affected by coupling and how the spread is altered in multi-model and multi-scenario ensembles of coupled models compared with uncoupled ones.
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| 9. |
- Heinzemann, Christian, et al.
(författare)
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A discipline-spanning development process for self-adaptive mechatronic systems
- 2013
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Ingår i: ACM International Conference Proceeding Series, Proc. of the International Conference on Software and Systems Process (ICSSP), May 18-19, San Francisco, CA, USA, 2013, s. 36-45. - New York, NY, USA : Association for Computing Machinery (ACM). - 9781450320627
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Konferensbidrag (refereegranskat)abstract
- Technical systems contain mechanical, electrical, and software parts. Consequently, they are developed by engineers of the respective disciplines. However, current industrial practice as well as existing development processes do not account for the required tight integration between the engineers of the different disciplines. Processes become even more complex, when self-adaptive systems are built. In this paper, we present a development process for selfadaptive mechatronic systems which particularly addresses the integration between the disciplines concerned with the development of software, namely control and software engineering. We illustrate the process by presenting examples from the development of autonomous railway vehicles which build convoys to improve energy efficiency.
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| 10. |
- Heinzemann, Christian, et al.
(författare)
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Generating Simulink and Stateflow Models From Software Specifications
- 2012
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Ingår i: Proceedings of the 12h International Design Conference DESIGN 2012. May 2012.
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Konferensbidrag (refereegranskat)abstract
- Much of the innovation in today’s technical systems is only possible by the use of embedded software. This is especially true in the case of system of systems where autonomous systems coordinate using complex message-based communication protocols. MechatronicUML is a modeling language for these systems that exploits formal methods to verify that safety requirements are always satisfied. In this paper, we present how we integrate MechatronicUML in the Simulink tool chain by means of model generation. We specifically discuss how the verified behavior is preserved in the generated models.
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| 11. |
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| 12. |
- Loza, M. J., et al.
(författare)
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Validated and longitudinally stable asthma phenotypes based on cluster analysis of the ADEPT study
- 2016
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Ingår i: Respiratory Research. - : Springer Nature. - 1465-9921 .- 1465-993X. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Asthma is a disease of varying severity and differing disease mechanisms. To date, studies aimed at stratifying asthma into clinically useful phenotypes have produced a number of phenotypes that have yet to be assessed for stability and to be validated in independent cohorts. The aim of this study was to define and validate, for the first time ever, clinically driven asthma phenotypes using two independent, severe asthma cohorts: ADEPT and U-BIOPRED. Methods: Fuzzy partition-around-medoid clustering was performed on pre-specified data from the ADEPT participants (n = 156) and independently on data from a subset of U-BIOPRED asthma participants (n = 82) for whom the same variables were available. Models for cluster classification probabilities were derived and applied to the 12-month longitudinal ADEPT data and to a larger subset of the U-BIOPRED asthma dataset (n = 397). High and low type-2 inflammation phenotypes were defined as high or low Th2 activity, indicated by endobronchial biopsies gene expression changes downstream of IL-4 or IL-13. Results: Four phenotypes were identified in the ADEPT (training) cohort, with distinct clinical and biomarker profiles. Phenotype 1 was "mild, good lung function, early onset", with a low-inflammatory, predominantly Type-2, phenotype. Phenotype 2 had a "moderate, hyper-responsive, eosinophilic" phenotype, with moderate asthma control, mild airflow obstruction and predominant Type-2 inflammation. Phenotype 3 had a "mixed severity, predominantly fixed obstructive, non-eosinophilic and neutrophilic" phenotype, with moderate asthma control and low Type-2 inflammation. Phenotype 4 had a "severe uncontrolled, severe reversible obstruction, mixed granulocytic" phenotype, with moderate Type-2 inflammation. These phenotypes had good longitudinal stability in the ADEPT cohort. They were reproduced and demonstrated high classification probability in two subsets of the U-BIOPRED asthma cohort. Conclusions: Focusing on the biology of the four clinical independently-validated easy-to-assess ADEPT asthma phenotypes will help understanding the unmet need and will aid in developing tailored therapies. Trial registration:NCT01274507(ADEPT), registered October 28, 2010 and NCT01982162(U-BIOPRED), registered October 30, 2013.
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| 13. |
- Milosevic, Jelena, et al.
(författare)
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PPM1D is a neuroblastoma oncogene and therapeutic target in childhood neural tumors
- 2020
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Majority of cancers harbor alterations of the tumor suppressor TP53. However, childhood cancers, including unfavorable neuroblastoma, often lack TP53 mutations despite frequent loss of p53 function, suggesting alternative p53 inactivating mechanisms.Here we show that p53-regulating PPM1D at chromosome 17q22.3 is linked to aggressive tumors and poor prognosis in neuroblastoma. We identified that WIP1-phosphatase encoded by PPM1D, is activated by frequent segmental 17q-gain further accumulated during clonal evolution, gene-amplifications, gene-fusions or gain-of-function somatic and germline mutations. Pharmacological and genetic manipulation established WIP1 as a druggable target in neuroblastoma. Genome-scale CRISPR-Cas9 screening demonstrated PPM1D genetic dependency in TP53 wild-type neuroblastoma cell lines, and shRNA PPM1D knockdown significantly delayed in vivo tumor formation. Establishing a transgenic mouse model overexpressing PPM1D showed that these mice develop cancers phenotypically and genetically similar to tumors arising in mice with dysfunctional p53 when subjected to low-dose irradiation. Tumors include T-cell lymphomas harboring Notch1-mutations, Pten-deletions and p53-accumulation, adenocarcinomas and PHOX2B-expressing neuroblastomas establishing PPM1D as a bona fide oncogene in wtTP53 cancer and childhood neuroblastoma. Pharmacological inhibition of WIP1 suppressed the growth of neural tumors in nude mice proposing WIP1 as a therapeutic target in neural childhood tumors.
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| 17. |
- Priesterjahn, Claudia, et al.
(författare)
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Runtime Safety Analysis for Safe Reconfiguration
- 2012
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Ingår i: IEEE International Conference on Industrial Informatics (INDIN). - 1935-4576. - 9781467303118 ; , s. 1092-1097
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Konferensbidrag (refereegranskat)abstract
- Modern technical systems are increasingly built to exhibit self-x properties as, e.g., self-healing or self-optimization. For this, they require adaptation at runtime. This is even true for embedded or mechatronic systems which often operate in safety- critical environments. There, the effects of the adaptation with respect to safety must be analyzed carefully. However, not all parameters needed for safety analyses, e.g., the concrete system architecture, are known at design time. Consequently, safety analyses need to be executed during runtime. Current approaches of runtime safety analysis typically react to anomalies that already occurred in the system. Thus, unsafe system states cannot be excluded completely. We present a runtime safety analysis that prevents system states with an unacceptable risk that have not yet occurred. For this, we generate the reachable component structures at runtime and analyze them with respect to risk. The system is modified such that component structures with an unacceptable risk are not reachable any more and are thus prevented.
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| 18. |
- Staron, Miroslaw, 1977, et al.
(författare)
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Industrial Experiences from Evolving Measurement Systems into Self-Healing Systems for Improved Availability
- 2018
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Ingår i: Software, Practice & Experience. - : Wiley. - 0038-0644 .- 1097-024X. ; 48:3
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Tidskriftsartikel (refereegranskat)abstract
- Automated measurement programs are an efficient way of collecting, processing and visualizing measures in large software development companies. The number of measurements in these programs is usually large, which is caused by diversity of the needs of the stakeholders. In this paper we present the application of self-healing concepts to assure the availability of measurements to stakeholders without the need for effort-intensive and costly manual interventions of the operators. We study the measurement infrastructure at one of the development units of a large infrastructure provider. In this paper we present how MAPE-K model was instantiated in a simplistic manner in order to reduce the need for manual intervention in the operation of measurement systems. Based on the experiences from the two cases studied in this paper we show how an evolution towards self-healing measurement systems is done both with a dedicated failure taxonomy and with an effective straightforward handling of the most common errors in the execution. The mechanisms studied and presented in this paper show that self-healing provides significant improvements to the operation of the measurement program and reduces the need for daily oversight by an operator for the measurement systems.
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| 19. |
- Thienel, Matthias, et al.
(författare)
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Intranasal insulin decreases circulating cortisol concentrations during early sleep in elderly humans
- 2017
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 54, s. 170-174
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Tidskriftsartikel (refereegranskat)abstract
- Aging is associated with increases in hypothalamic-pituitary-adrenal (HPA) axis activity that can predispose to metabolic and cognitive impairments. We investigated in elderly and young subjects whether intranasal insulin administration to the human brain reduces early-sleep nadir concentrations of adrenocorticotropin and cortisol, that is, indicators of baseline HPA axis activity. In within-subject comparisons, intranasal insulin (160 IU) or placebo was administered to 14 elderly (mean age 70.0 years) and 30 young (23.6 years) healthy subjects before bedtime. Sleep was polysomno-graphically assessed and blood samples were repeatedly collected. Elderly compared with young participants displayed increased early-sleep cortisol concentrations (p < 0.04) and reductions in slow wave and REM sleep (p < 0.001). Insulin administration reduced cortisol levels between 2300 hours and 0020 hours in the elderly (p = 0.03) but not young participants (p = 0.56; p = 0.003 for interaction). Findings indicate that central nervous insulin acts as an inhibitory signal in basal HPA axis activity regulation and suggest that intranasal insulin may normalize sleep-associated stress axis activity in older age.
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| 21. |
- Zweifel, Roman, et al.
(författare)
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Why trees grow at night
- 2021
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Ingår i: New Phytologist. - : John Wiley & Sons. - 0028-646X .- 1469-8137. ; 231:6, s. 2174-2185
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Tidskriftsartikel (refereegranskat)abstract
- The timing of diel stem growth of mature forest trees is still largely unknown, as empirical data with high temporal resolution have not been available so far. Consequently, the effects of day-night conditions on tree growth remained uncertain. Here we present the first comprehensive field study of hourly-resolved radial stem growth of seven temperate tree species, based on 57 million underlying data points over a period of up to 8 yr. We show that trees grow mainly at night, with a peak after midnight, when the vapour pressure deficit (VPD) is among the lowest. A high VPD strictly limits radial stem growth and allows little growth during daylight hours, except in the early morning. Surprisingly, trees also grow in moderately dry soil when the VPD is low. Species-specific differences in diel growth dynamics show that species able to grow earlier during the night are associated with the highest number of hours with growth per year and the largest annual growth increment. We conclude that species with the ability to overcome daily water deficits faster have greater growth potential. Furthermore, we conclude that growth is more sensitive than carbon uptake to dry air, as growth stops before stomata are known to close.
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