| 1. |
- 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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| 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. |
- 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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| 5. |
- 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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| 7. |
- 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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| 10. |
- Elmqvist, Thomas, et al.
(författare)
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Benefits of restoring ecosystem services in urban areas
- 2015
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Ingår i: Current Opinion in Environmental Sustainability. - : Elsevier BV. - 1877-3435 .- 1877-3443. ; 14, s. 101-108
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Tidskriftsartikel (refereegranskat)abstract
- Cities are a key nexus of the relationship between people and nature and are huge centers of demand for ecosystem services and also generate extremely large environmental impacts. Current projections of rapid expansion of urban areas present fundamental challenges and also opportunities to design more livable, healthy and resilient cities (e.g. adaptation to climate change effects). We present the results of an analysis of benefits of ecosystem services in urban areas. Empirical analyses included estimates of monetary benefits from urban ecosystem services based on data from 25 urban areas in the USA, Canada, and China. Our results show that investing in ecological infrastructure in cities, and the ecological restoration and rehabilitation of ecosystems such as rivers, lakes, and woodlands occurring in urban areas, may not only be ecologically and socially desirable, but also quite often, economically advantageous, even based on the most traditional economic approaches.
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| 11. |
- Jungo, Katharina Tabea, et al.
(författare)
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General practitioners' deprescribing decisions in older adults with polypharmacy : a case vignette study in 31 countries
- 2021
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Ingår i: BMC Geriatrics. - : BioMed Central (BMC). - 1471-2318. ; 21:1, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- Background General practitioners (GPs) should regularly review patients' medications and, if necessary, deprescribe, as inappropriate polypharmacy may harm patients' health. However, deprescribing can be challenging for physicians. This study investigates GPs' deprescribing decisions in 31 countries. Methods In this case vignette study, GPs were invited to participate in an online survey containing three clinical cases of oldest-old multimorbid patients with potentially inappropriate polypharmacy. Patients differed in terms of dependency in activities of daily living (ADL) and were presented with and without history of cardiovascular disease (CVD). For each case, we asked GPs if they would deprescribe in their usual practice. We calculated proportions of GPs who reported they would deprescribe and performed a multilevel logistic regression to examine the association between history of CVD and level of dependency on GPs' deprescribing decisions. Results Of 3,175 invited GPs, 54% responded (N = 1,706). The mean age was 50 years and 60% of respondents were female. Despite differences across GP characteristics, such as age (with older GPs being more likely to take deprescribing decisions), and across countries, overall more than 80% of GPs reported they would deprescribe the dosage of at least one medication in oldest-old patients (> 80 years) with polypharmacy irrespective of history of CVD. The odds of deprescribing was higher in patients with a higher level of dependency in ADL (OR =1.5, 95%CI 1.25 to 1.80) and absence of CVD (OR =3.04, 95%CI 2.58 to 3.57). Interpretation The majority of GPs in this study were willing to deprescribe one or more medications in oldest-old multimorbid patients with polypharmacy. Willingness was higher in patients with increased dependency in ADL and lower in patients with CVD.
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| 12. |
- 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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| 14. |
- 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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| 19. |
- 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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