| 1. |
- Müller, T D, et al.
(författare)
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Ghrelin.
- 2015
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Ingår i: Molecular metabolism. - : Elsevier BV. - 2212-8778. ; 4:6, s. 437-60
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Tidskriftsartikel (refereegranskat)abstract
- The gastrointestinal peptide hormone ghrelin was discovered in 1999 as the endogenous ligand of the growth hormone secretagogue receptor. Increasing evidence supports more complicated and nuanced roles for the hormone, which go beyond the regulation of systemic energy metabolism.
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| 2. |
- Aguiar, A., et al.
(författare)
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Practices in prescribing protein substitutes for PKU in Europe : No uniformity of approach
- 2015
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Ingår i: Molecular Genetics and Metabolism. - : Elsevier BV. - 1096-7192 .- 1096-7206. ; 115:1, s. 17-22
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Tidskriftsartikel (refereegranskat)abstract
- Background: There appears little consensus concerning protein requirements in phenylketonuria (PKU). Methods: A questionnaire completed by 63 European and Turkish IMD centres from 18 countries collected data on prescribed total protein intake (natural/intact protein and phenylalanine-free protein substitute [PS]) by age, administration frequency and method, monitoring, and type of protein substitute. Data were analysed by European region using descriptive statistics. Results: The amount of total protein (from PS and natural/intact protein) varied according to the European region. Higher median amounts of total protein were prescribed in infants and children in Northern Europe (n = 24 centres) (infants <1 year, >2-3 g/kg/day; 1-3 years of age, >2-3 g/kg/day; 4-10 years of age, >1.5-2.5 g/kg/day) and Southern Europe (n = 10 centres) (infants <1 year, 2.5 g/kg/day, 1-3 years of age, 2 g/kg/day; 4-10 years of age, 1.5-2 g/kg/day), than by Eastern Europe (n = 4 centres) (infants <1 year, 2.5 g/kg/day, 1-3 years of age, >2-2.5 g/kg/day; 4-10 years of age, >1.5-2 g/kg/day) and with Western Europe (n = 25 centres) giving the least (infants <1 year, >2-2.5 g/kg/day, 1-3 years of age, 1.5-2 g/kg/day; 4-10 years of age, 1-1.5 g/kg/day). Total protein prescription was similar in patients aged >10 years (1-1.5 g/kg/day) and maternal patients (1-1.5 g/kg/day). Conclusions: The amounts of total protein prescribed varied between European countries and appeared to be influenced by geographical region. In PKU, all gave higher than the recommended 2007 WHO/FAO/UNU safe levels of protein intake for the general population.
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| 3. |
- Yeo, G. S. H., et al.
(författare)
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The melanocortin pathway and energy homeostasis: From discovery to obesity therapy
- 2021
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Ingår i: Molecular Metabolism. - : Elsevier BV. - 2212-8778. ; 48
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Tidskriftsartikel (refereegranskat)abstract
- Background: Over the past 20 years, insights from human and mouse genetics have illuminated the central role of the brain leptin-melanocortin pathway in controlling mammalian food intake, with genetic disruption resulting in extreme obesity, and more subtle polymorphic variations influencing the population distribution of body weight. At the end of 2020, the U.S. Food and Drug Administration (FDA) approved setmelanotide, a melanocortin 4 receptor agonist, for use in individuals with severe obesity due to either pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency. Scope of review: Herein, we chart the melanocortin pathway & rsquo;s history, explore its pharmacology, genetics, and physiology, and describe how a neuropeptidergic circuit became an important druggable obesity target. Major conclusions: Unravelling the genetics of the subset of severe obesity has revealed the importance of the melanocortin pathway in appetitive control; coupling this with studying the molecular pharmacology of compounds that bind melanocortin receptors has brought a new obesity drug to the market. This process provides a drug discovery template for complex disorders, which for setmelanotide took 25 years to transform from a single gene into an approved drug.
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| 4. |
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| 6. |
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| 7. |
- Hawinkels, L J A C, et al.
(författare)
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Interaction with colon cancer cells hyperactivates TGF-β signaling in cancer-associated fibroblasts
- 2014
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 33:1, s. 97-107
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Tidskriftsartikel (refereegranskat)abstract
- The interaction between epithelial cancer cells and cancer-associated fibroblasts (CAFs) has a major role in cancer progression and eventually in metastasis. In colorectal cancer (CRC), CAFs are present in high abundance, but their origin and functional interaction with epithelial tumor cells has not been elucidated. In this study we observed strong activation of the transforming growth factor-β (TGF-β)/Smad signaling pathway in CRC CAFs, accompanied by decreased signaling in epithelial tumor cells. We evaluated the TGF-β1 response and the expression of target genes including matrix metalloproteinases (MMPs) and plasminogen activator inhibitor (PAI)-1 of various epithelial CRC cell lines and primary CAFs in vitro. TGF-β1 stimulation caused high upregulation of MMPs, PAI-1 and TGF-β1 itself. Next we showed that incubation of CAFs with conditioned medium (CM) from epithelial cancer cells led to hyperactivation of the TGF-β signaling pathway, enhanced expression of target genes like PAI-1, and the expression of α-smooth muscle actin (α-SMA). We propose that the interaction of tumor cells with resident fibroblasts results in hyperactivated TGF-β1 signaling and subsequent transdifferentiation of the fibroblasts into α-SMA-positive CAFs. In turn this leads to cumulative production of TGF-β and proteinases within the tumor microenvironment, creating a cancer-promoting feedback loop.
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| 8. |
- Tremblay, Mark S, et al.
(författare)
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Sedentary Behavior Research Network (SBRN) - Terminology Consensus Project process and outcome.
- 2017
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Ingår i: The international journal of behavioral nutrition and physical activity. - : Springer Science and Business Media LLC. - 1479-5868. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The prominence of sedentary behavior research in health science has grown rapidly. With this growth there is increasing urgency for clear, common and accepted terminology and definitions. Such standardization is difficult to achieve, especially across multi-disciplinary researchers, practitioners, and industries. The Sedentary Behavior Research Network (SBRN) undertook a Terminology Consensus Project to address this need.First, a literature review was completed to identify key terms in sedentary behavior research. These key terms were then reviewed and modified by a Steering Committee formed by SBRN. Next, SBRN members were invited to contribute to this project and interested participants reviewed and provided feedback on the proposed list of terms and draft definitions through an online survey. Finally, a conceptual model and consensus definitions (including caveats and examples for all age groups and functional abilities) were finalized based on the feedback received from the 87 SBRN member participants who responded to the original invitation and survey.Consensus definitions for the terms physical inactivity, stationary behavior, sedentary behavior, standing, screen time, non-screen-based sedentary time, sitting, reclining, lying, sedentary behavior pattern, as well as how the terms bouts, breaks, and interruptions should be used in this context are provided.It is hoped that the definitions resulting from this comprehensive, transparent, and broad-based participatory process will result in standardized terminology that is widely supported and adopted, thereby advancing future research, interventions, policies, and practices related to sedentary behaviors.
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| 9. |
- Blösch, Günter, et al.
(författare)
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Twenty-three unsolved problems in hydrology (UPH) - a community perspective
- 2019
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Ingår i: Hydrological Sciences Journal. - : Informa UK Limited. - 0262-6667 .- 2150-3435. ; 64:10, s. 1141-1158
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Tidskriftsartikel (refereegranskat)abstract
- This paper is the outcome of a community initiative to identify major unsolved scientific problems in hydrology motivated by a need for stronger harmonisation of research efforts. The procedure involved a public consultation through online media, followed by two workshops through which a large number of potential science questions were collated, prioritised, and synthesised. In spite of the diversity of the participants (230 scientists in total), the process revealed much about community priorities and the state of our science: a preference for continuity in research questions rather than radical departures or redirections from past and current work. Questions remain focused on the process-based understanding of hydrological variability and causality at all space and time scales. Increased attention to environmental change drives a new emphasis on understanding how change propagates across interfaces within the hydrological system and across disciplinary boundaries. In particular, the expansion of the human footprint raises a new set of questions related to human interactions with nature and water cycle feedbacks in the context of complex water management problems. We hope that this reflection and synthesis of the 23 unsolved problems in hydrology will help guide research efforts for some years to come.
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| 10. |
- Broers, C J M, et al.
(författare)
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The post-infarction nurse practitioner project : A prospective study comparing nurse intervention with conventional care in a non-high-risk myocardial infarction population.
- 2009
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Ingår i: Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation. - 1568-5888. ; 17:2, s. 61-7
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To confirm the feasibility of nurse practitioner interventionin non-high-risk patients with recent myocardial infarction (MI). DESIGN: Observational study. SETTING: Acute coronary care unit in a teaching hospital. METHODS: We performed an open-label feasibility study to identify non-high-risk MI patients and evaluate the outcome of a new nurse practitioner intervention programme. The initial pilot phase served to identify the non-high-risk population. In the subsequent confirmation phase, 500 consecutive non-high-risk post-MI patients with preserved LV function without heart failure were included to receive nurse practitioner management. The nurse practitioner intervention started on transfer from the coronary care unit to the cardiology ward and continued thereafter for up to 30 days. MAIN OUTCOME MEASURES: Time to first event analysis of death from all causes or repeat myocardial infarction. RESULTS: 500 Patients without signs of heart failure or depressed LV function were identified as nonhigh- risk and eligible for inclusion in the nurse practitioner intervention programme. In the implementation phase, none of the patients died and 0.9% developed a repeat myocardial infarction after 30 days of follow-up. Compared with the pilot phase, patients in the implementation phase spent fewer days in hospital (mean 11.1 versus 6.2 days; p<0.001). CONCLUSION: It is feasible to identify non-high-risk post-MI patients, who can be managed adequately by a nurse practitioner. Embedding experienced nurse practitioners within critical care pathways may result in significant decreases in length of hospital stay. (Neth Heart J 2009;17:61-7.Neth Heart J 2009;17:61-7.).
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| 11. |
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| 12. |
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| 13. |
- Molenaar, Jan J., et al.
(författare)
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Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 483:7391, s. 107-589
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Tidskriftsartikel (refereegranskat)abstract
- Neuroblastomais a childhood tumour of the peripheral sympathetic nervous system. The pathogenesis has for a long time been quite enigmatic, as only very few gene defects were identified in this often lethal tumour(1). Frequently detected gene alterations are limited to MYCN amplification (20%) and ALK activations (7%)(2-5). Here we present a whole-genome sequence analysis of 87 neuroblastoma of all stages. Few recurrent amino-acid-changing mutations were found. In contrast, analysis of structural defects identified a local shredding of chromosomes, known as chromothripsis, in 18% of high-stage neuroblastoma(6). These tumours are associated with a poor outcome. Structural alterations recurrently affected ODZ3, PTPRD and CSMD1, which are involved in neuronal growth cone stabilization(7-9). In addition, ATRX, TIAM1 and a series of regulators of the Rac/Rho pathway were mutated, further implicating defects in neuritogenesis in neuroblastoma. Most tumours with defects in these genes were aggressive high-stage neuroblastomas, but did not carry MYCN amplifications. The genomic landscape of neuroblastoma therefore reveals two novel molecular defects, chromothripsis and neuritogenesis gene alterations, which frequently occur in high-risk tumours.
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| 14. |
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| 15. |
- van Rijn, Margreet, et al.
(författare)
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A Survey of Natural Protein Intake in Dutch Phenylketonuria Patients : Insight into Estimation or Measurement of Dietary Intake
- 2008
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Ingår i: Journal of the American Dietetic Association. - : Elsevier BV. - 0002-8223. ; 108:10, s. 1704-1707
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated which methods patients and parents used to determine phenylalanine (Phe) intake and the relationship between the methods applied, age, and blood Phe concentration, as this practice had not been studied before in relation to metabolic control. A questionnaire was sent to 327 Dutch phenylketonuria patients (age 0-29 years) to investigate the method used to determine Phe intake (either by estimation, exact measurement, or a combination of both). Mean blood Phe concentration of each individual patient was related to the method reported to be used. Three different age groups (<10 years, ≥10-15 years, and ≥16 years) were distinguished. The response rate for the questionnaires was 73%. In these 188 patients, data for both Phe concentrations and questionnaires could be used. Of these, 75 used exact measurement, 75 used estimation, and 38 used both methods. The number of patients that estimated Phe intake clearly increased with age. Whatever method was used, an increase in Phe concentrations was seen with age. During childhood, exact measurement was used more frequently, and from adolescence on estimation was used more frequently. The method (exact measurement and/or estimation) did not result in statistically different Phe concentrations in any of the three age groups, although blood Phe concentration tended to be lower in adolescence using exact measurement. Data suggest that estimation and exact measurement of Phe intake are both reliable methods. Therefore, in addition to exact measurement, patients should be instructed in both methods at an early age, so that both methods can be used adequately.
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| 16. |
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| 17. |
- Basten, B., et al.
(författare)
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Modular language implementation in Rascal - experience report
- 2015
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Ingår i: Science of Computer Programming. - : Elsevier BV. - 0167-6423. ; 114, s. 7-19
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Tidskriftsartikel (refereegranskat)abstract
- All software evolves, and programming languages and programming language tools are no exception. And just like in ordinary software construction, modular implementations can help ease the process of changing a language implementation and its dependent tools. However, the syntactic and semantic dependencies between language features make this a challenging problem. In this paper we detail how programming languages can be implemented in a modular fashion using the RASCAL meta-programming language. RASCAL supports extensible definition of concrete syntax, abstract syntax and operations on concrete and abstract syntax trees like matching, traversal and transformation. As a result, new language features can be added without having to change existing code. As a case study, we detail our solution of the LDTA'11 Tool Challenge: a modular implementation of OBERON-0, a relatively simple imperative programming language. The approach we sketch can be applied equally well to the implementation of domain-specific languages.
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| 18. |
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| 19. |
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| 20. |
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| 21. |
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| 22. |
- Kattner, Nicole, et al.
(författare)
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Development and validation of a quantitative electron microscopy score to assess acute cellular stress in the human exocrine pancreas
- 2021
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Ingår i: Journal of Pathology: Clinical Research. - : Wiley. - 2056-4538. ; 7:2, s. 173-187
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Tidskriftsartikel (refereegranskat)abstract
- The pancreas is particularly sensitive to acute cellular stress, but this has been difficult to evaluate using light microscopy. Pancreatic ischaemia associated with deceased organ donation negatively impacts whole-organ and isolated-islet transplantation outcomes. Post-mortem changes have also hampered accurate interpretation of ante-mortem pancreatic pathology. A rigorous histological scoring system accurately quantifying ischaemia is required to experimentally evaluate innovations in organ preservation and to increase rigour in clinical/research evaluation of underlying pancreatic pathology. We developed and validated an unbiased electron microscopy (EM) score of acute pancreatic exocrine cellular stress in deceased organ donor cohorts (development [n = 28] and validation [n = 16]). Standardised assessment led to clearly described numerical scores (0–3) for nuclear, mitochondrial and endoplasmic reticulum (ER) morphology and intracellular vacuolisation; with a maximum (worst) aggregate total score of 12. In the Validation cohort, a trend towards higher scores was observed for tail versus head regions (nucleus score following donation after brainstem death [DBD]: head 0.67 ± 0.19; tail 0.86 ± 0.11; p = 0.027) and donation after circulatory death (DCD) versus DBD (mitochondrial score: DCD (head + tail) 2.59 ± 0.16; DBD (head + tail) 2.38 ± 0.21; p = 0.004). Significant mitochondrial changes were seen ubiquitously even with short cold ischaemia, whereas nuclear and vacuolisation changes remained mild even after prolonged ischaemia. ER score correlated with cold ischaemia time (CIT) following DBD (pancreatic tail region: r = 0.796; p = 0.018). No relationships between CIT and EM scores were observed following DCD. In conclusion, we have developed and validated a novel EM score providing standardised quantitative assessment of subcellular ultrastructural morphology in pancreatic acinar cells. This provides a robust novel tool for gold standard measurement of acute cellular stress in studies evaluating surrogate measures of peri-transplant ischaemia, organ preservation technologies and in samples obtained for detailed pathological examination of underlying pancreatic pathology.
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| 23. |
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| 24. |
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| 25. |
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| 26. |
- Li, YH, et al.
(författare)
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Inhibition of macrophage proinflammatory cytokine expression by steroids and recombinant IL-10
- 2001
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Ingår i: Biology of the neonate. - : S. Karger AG. - 0006-3126. ; 80:2, s. 124-132
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Tidskriftsartikel (refereegranskat)abstract
- Chronic lung disease (CLD) of prematurity is a prolonged respiratory failure in very-low-birth-weight neonates. Proinflammatory cytokines have been implicated in the development of CLD. Steroids have been shown to produce some improvement in neonates with this disease. The purpose of this study was to evaluate the downregulation of these proinflammatory cytokines by dexamethasone, budesonide and recombinant IL-10 (rIL-10) in order to elucidate the mechanism of the clinical benefit of steroids in babies. Our results showed that dexamethasone, budesonide and rIL-10 significantly inhibited both IL-6 and TNF-α production in the THP-1 cell line stimulated by lipopolysaccharide and <i>Ureaplasma urealyticum</i> antigen. Similar effects were found in macrophages from tracheobronchial aspirate fluid from newborn infants. In the rat alveolar macrophage cell line, steroids inhibited IL-6 and TNF-α production, while rat rIL-10 did not significantly decrease production. In conclusion, steroids and human rIL-10 were able to downregulate proinflammatory cytokine production, which may explain the beneficial effect of steroids and suggests that rIL-10 could be tried as an anti-inflammatory agent in neonates with a high risk of CLD.
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| 27. |
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| 28. |
- Loyen, Anne, et al.
(författare)
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Sedentary Time and Physical Activity Surveillance Through Accelerometer Pooling in Four European Countries
- 2017
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Ingår i: Sports Medicine. - : Springer Science and Business Media LLC. - 0112-1642 .- 1179-2035. ; 47:7, s. 1421-1435
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The objective of this study was to pool, harmonise and re-analyse national accelerometer data from adults in four European countries in order to describe population levels of sedentary time and physical inactivity. Methods: Five cross-sectional studies were included from England, Portugal, Norway and Sweden. ActiGraph accelerometer count data were centrally processed using the same algorithms. Multivariable logistic regression analyses were conducted to study the associations of sedentary time and physical inactivity with sex, age, weight status and educational level, in both the pooled sample and the separate study samples. Results: Data from 9509 participants were used. On average, participants were sedentary for 530 min/day, and accumulated 36 min/day of moderate to vigorous intensity physical activity. Twenty-three percent accumulated more than 10 h of sedentary time/day, and 72% did not meet the physical activity recommendations. Nine percent of all participants were classified as high sedentary and low active. Participants from Norway showed the highest levels of sedentary time, while participants from England were the least physically active. Age and weight status were positively associated with sedentary time and not meeting the physical activity recommendations. Men and higher-educated people were more likely to be highly sedentary, while women and lower-educated people were more likely to be inactive. Conclusions: We found high levels of sedentary time and physical inactivity in four European countries. Older people and obese people were most likely to display these behaviours and thus deserve special attention in interventions and policy planning. In order to monitor these behaviours, accelerometer-based cross-European surveillance is recommended.
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| 29. |
- Nguyen, TN, et al.
(författare)
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Physical Activity and Plasma Glucose Control among Diabetic Patients Attending Outpatients Clinics in Hanoi, Vietnam
- 2021
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Ingår i: International journal of environmental research and public health. - : MDPI AG. - 1660-4601. ; 18:3
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Tidskriftsartikel (refereegranskat)abstract
- Reaching the recommendation on physical activity (PA) for health is highly important to effectively manage blood glucose in patients with type 2 diabetes (T2D). The aims of this study were to assess the level and pattern of PA among T2D outpatients and to relate PA levels to glucose control. A cross-sectional study was conducted in outpatient clinics in Hanoi, Vietnam. PA levels were reported using the Global Physical Activity Questionnaire (GPAQ) version 2.0. Participants meeting the WHO recommendations on PA for health or not were respectively categorized as “sufficiently active” and “insufficiently active”. FPG < 7.2 mmol/L was defined as controlled plasma glucose. In total, 407 participants with T2D (55% women, mean (SD) age 61.6 (9.7) years) were included. The fraction of T2D outpatients reporting as insufficiently active was 21%. The lowest amount of energy expenditure was from transport activities (travel from and to places). On multivariate logistic regression, being sufficiently active was associated with a two-fold increased likelihood of having better glycemic control. The findings warrant action plans to increase physical activity in general and in specific active transport for T2D patients in Vietnam.
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| 30. |
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| 31. |
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| 32. |
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| 33. |
- Ploeg, Jeroen, et al.
(författare)
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Cooperative Automated Maneuvering at the 2016 Grand Cooperative Driving Challenge
- 2018
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Ingår i: IEEE transactions on intelligent transportation systems (Print). - Piscataway : IEEE Press. - 1524-9050 .- 1558-0016. ; 19:4, s. 1213-1226
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Tidskriftsartikel (refereegranskat)abstract
- Cooperative adaptive cruise control and platooning are well- known applications in the field of cooperative automated driving. However, extension toward maneuvering is desired to accommodate common highway maneuvers, such as merging, and to enable urban applications. To this end, a layered control architecture is adopted. In this architecture, the tactical layer hosts the interaction protocols, describing the wireless information exchange to initiate the vehicle maneuvers, supported by a novel wireless message set, whereas the operational layer involves the vehicle controllers to realize the desired maneuvers. This hierarchical approach was the basis for the Grand Cooperative Driving Challenge (GCDC), which was held in May 2016 in The Netherlands. The GCDC provided the opportunity for participating teams to cooperatively execute a highway lane-reduction scenario and an urban intersection-crossing scenario. The GCDC was set up as a competition and, hence, also involving assessment of the teams' individual performance in a cooperative setting. As a result, the hierarchical architecture proved to be a viable approach, whereas the GCDC appeared to be an effective instrument to advance the field of cooperative automated driving.
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| 34. |
- Steyer, J. -Sebastien, et al.
(författare)
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A new vertebrate Lagerstatte from the Lower Permian of France (Franchesse, Massif Central) : palaeoenvironmental implications for the Bourbon-l'Archambault basin
- 2012
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Ingår i: Bulletin de la Société Géologique de France. - 0037-9409 .- 1777-5817. ; 183:6, s. 509-515
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Tidskriftsartikel (refereegranskat)abstract
- A new vertebrate locality from the Lower Permian (Cisuralian) of the Bourbon-l'Archambault basin (Massif Central, France) is reported and its associated flora and fauna preliminarily described. This locality corresponds to a mass mortality assemblage deposited in an aquatic environment. Interestingly, it has yielded hundreds of exceptionally well preserved seymouriamorph specimens, all referred to Discosauriscus austriacus. This exquisite assemblage corresponds to the first seymouriamorph Lagerstatte and the first record of D. austriacus outside the Boskovice basin in Czechia. It enlarges the geographical distribution of the species during the Early Permian, and has new palaeoenvironmental implications regarding the Palaeozoic Bourbon-l'Archambault basin.
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| 39. |
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| 40. |
- van der Ploeg, Milly A., et al.
(författare)
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Patient Characteristics and General Practitioners' Advice to Stop Statins in Oldest-Old Patients : a Survey Study Across 30 Countries
- 2019
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Ingår i: Journal of general internal medicine. - : Springer. - 0884-8734 .- 1525-1497. ; 34:9, s. 1751-1757
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Tidskriftsartikel (refereegranskat)abstract
- Background Statins are widely used to prevent cardiovascular disease (CVD). With advancing age, the risks of statins might outweigh the potential benefits. It is unclear which factors influence general practitioners' (GPs) advice to stop statins in oldest-old patients. Objective To investigate the influence of a history of CVD, statin-related side effects, frailty and short life expectancy, on GPs' advice to stop statins in oldest-old patients. Design We invited GPs to participate in this case-based survey. GPs were presented with 8 case vignettes describing patients > 80 years using a statin, and asked whether they would advise stopping statin treatment. Main Measures Cases varied in history of CVD, statin-related side effects and frailty, with and without shortened life expectancy (< 1 year) in the context of metastatic, non-curable cancer. Odds ratios adjusted for GP characteristics (ORadj) were calculated for GPs' advice to stop. Key Results Two thousand two hundred fifty GPs from 30 countries participated (median response rate 36%). Overall, GPs advised stopping statin treatment in 46% (95%CI 45-47) of the case vignettes; with shortened life expectancy, this proportion increased to 90% (95CI% 89-90). Advice to stop was more frequent in case vignettes without CVD compared to those with CVD (ORadj 13.8, 95%CI 12.6-15.1), with side effects compared to without ORadj 1.62 (95%CI 1.5-1.7) and with frailty (ORadj 4.1, 95%CI 3.8-4.4) compared to without. Shortened life expectancy increased advice to stop (ORadj 50.7, 95%CI 45.5-56.4) and was the strongest predictor for GP advice to stop, ranging across countries from 30% (95%CI 19-42) to 98% (95% CI 96-99). Conclusions The absence of CVD, the presence of statin-related side effects, and frailty were all independently associated with GPs' advice to stop statins in patients aged > 80 years. Overall, and within all countries, cancer-related short life expectancy was the strongest independent predictor of GPs' advice to stop statins.
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