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  • Sumnik, Z., et al. (author)
  • Persistent heterogeneity in diabetes technology reimbursement for children with type 1 diabetes: The SWEET perspective
  • 2019
  • In: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 20:4, s. 434-443
  • Journal article (peer-reviewed)abstract
    • Background: Frequent use of modern diabetes technologies increases the chance for optimal type 1 diabetes (T1D) control. Limited reimbursement influences the access of patients with T1D to these modalities and could worsen their prognosis. We aimed to describe the situation of reimbursement for insulins, glucometers, insulin pumps (CSII) and continuous glucose monitoring (CGM) for children with T1D in European countries participating in the SWEET Project and to compare data from EU countries with data from our previous study in 2009. Methods: The study was conducted between March 2017 and August 2017. First, we approached diabetes technology companies with a survey to map the reimbursement of insulins and diabetic devices. The data collected from these companies were then validated by members of the SWEET consortium. Results: We collected data from 29 European countries, whereas all types of insulins are mostly fully covered, heterogeneity was observed regarding the reimbursement of strips for glucometers (from 90 strips/month to no limit). CSII is readily available in 20 of 29 countries. Seven countries reported significant quota issues or obstacles for CSII prescription, and two countries had no CSII reimbursement. CGM is at least partially reimbursed in 17 of 29 countries. The comparison with the 2009 study showed an increasing availability of CSII and CGM across the EU. Conclusions: Although innovative diabetes technology is available, a large proportion of children with T1D still do not benefit from it due to its limited reimbursement. © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
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  • Bergman, Peter N., et al. (author)
  • Do job demands and job control affect problem-solving?
  • 2012
  • In: Work. - : IOS Press. - 1051-9815 .- 1875-9270. ; 42:2, s. 195-203:42, s. 195-203
  • Journal article (peer-reviewed)abstract
    • Objective: The Job Demand Control model presents combinations of working conditions that may facilitate learning, the active learning hypothesis, or have detrimental effects on health, the strain hypothesis. To test the active learning hypothesis, this study analysed the effects of job demands and job control on general problem-solving strategies. Participants: A population-based sample of 4,636 individuals (55% women, 45% men) with the same job characteristics measured at two times with a three year time lag was used. Methods: Main effects of demands, skill discretion, task authority and control, and the combined effects of demands and control were analysed in logistic regressions, on four outcomes representing general problem-solving strategies. Results: Those reporting high on skill discretion, task authority and control, as well as those reporting high demand/high control and low demand/high control job characteristics were more likely to state using problem solving strategies. Conclusions: Results suggest that working conditions including high levels of control may affect how individuals cope with problems and that workplace characteristics may affect behaviour in the non-work domain.
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  • Hodik, Monika, et al. (author)
  • Enterovirus infection of human islets of Langerhans affects beta-cell function resulting in disintegrated islets, decreased glucose stimulated insulin secretion and loss of Golgi structure
  • 2016
  • In: BMJ OPEN DIABETES RESEARCH & CARE. - : BMJ. - 2052-4897. ; 4:1
  • Journal article (peer-reviewed)abstract
    • Aims/hypothesis: In type 1 diabetes (T1D), most insulin-producing beta cells are destroyed, but the trigger is unknown. One of the possible triggers is a virus infection and the aim of this study was to test if enterovirus infection affects glucose stimulated insulin secretion and the effect of virus replication on cellular macromolecules and organelles involved in insulin secretion. Methods: Isolated human islets were infected with different strains of coxsackievirus B (CVB) virus and the glucose-stimulated insulin release (GSIS) was measured in a dynamic perifusion system. Classical morphological electron microscopy, large-scale electron microscopy, so-called nanotomy, and immunohistochemistry were used to study to what extent virus-infected beta cells contained insulin, and real-time PCR was used to analyze virus induced changes of islet specific genes. Results: In islets infected with CVB, GSIS was reduced in correlation with the degree of virus-induced islet disintegration. The expression of the gene encoding insulin was decreased in infected islets, whereas the expression of glucagon was not affected. Also, in islets that were somewhat disintegrated, there were uninfected beta cells. Ultrastructural analysis revealed that virus particles and virus replication complexes were only present in beta cells. There was a significant number of insulin granules remaining in the virus-infected beta cells, despite decreased expression of insulin mRNA. In addition, no typical Golgi apparatus was detected in these cells. Exposure of islets to synthetic dsRNA potentiated glucose-stimulated insulin secretion. Conclusions/interpretation: Glucose-stimulated insulin secretion; organelles involved in insulin secretion and gene expression were all affected by CVB replication in beta cells.
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  • Ivarsson, Ylva, 1976- (author)
  • Evolutionary Analysis and Posttranslational Chemical Modifications in Protein Redesign : A Study on Mu Class Glutathione Transferases
  • 2006
  • Doctoral thesis (other academic/artistic)abstract
    • Glutathione transferases (GSTs) constitute a family of multifarious enzymes that conjugate glutathione (GSH) with a wide range of electrophiles. GSTs are grouped into different classes based on protein sequence similarities. Despite high sequence identities between GSTs of the same class they often display different substrate specificites. Human GST M1-1 is efficiently catalyzing the conjugation of GSH and various epoxide substrates, whereas the 84% sequence-identical GST M2-2 has low activities with the same substrates.Evolutionary rate analysis was used to identify hypervariable amino acid positions among GST Mu class sequences. A Thr to Ser conversion of the variable residue 210 in GST M2-2 elicited a drastic increase in catalytic activity with epoxides, which is the characteristic activity of GST M1-1. This provides support for the usefulness of evolutionary analysis in identifying functionally important residues, although the additional mutations of two other variable residues did not confer any noteworthy changes in activity.To further investigate the functional importance of residue T210 in GST M2-2 it was replaced by all other commonly occurring amino acids. The replacements caused marked changes in substrate specificity, stability, and expressivity, indicating how functionalities of a duplicated Mu class GST may easily be altered by point mutations. The stereo- and regioselectivity in epoxide-conjugation catalyzed by GSTs M1-1 and M2-2 was investigated. The results show that a serine in position 210 is beneficial for high enantioselectivity with trans-stilbene oxide. However, an alanine in position 210 is more favorable for stereo- and regioselectivity with the smaller epoxide substrate styrene-7,8-oxide. The low enantioselectivity of GST M1-1 was improved 10- and 9- fold with styrene-7,8-oxide and 1-phenylpropylene oxide, respectively, through different combination of site-specific mutations and posttranslational chemical modifications. The approach can be employed in more extensive screening experiments where a large variety of modifications easily can be tested.
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  • Koc-Januchta, Marta, 1977-, et al. (author)
  • Visualizers versus verbalizers : Effects of cognitive style on learning with texts and pictures - An eye-tracking study
  • 2017
  • In: Computers in human behavior. - : Elsevier. - 0747-5632 .- 1873-7692. ; 68, s. 170-179
  • Journal article (peer-reviewed)abstract
    • This study was conducted in order to examine the differences between visualizers and verbalizers in the way they gaze at pictures and texts while learning. Using a collection of questionnaires, college students were classified according to their visual or verbal cognitive style and were asked to learn about two different, in terms of subject and type of knowledge, topics by means of text-picture combinations. Eye-tracking was used to investigate their gaze behavior. The results show that visualizers spent significantly more time inspecting pictures than verbalizers, while verbalizers spent more time inspecting texts. Results also suggest that both visualizers' and verbalizers' way of learning is active but mostly within areas providing the source of information in line with their cognitive style (pictures or text). Verbalizers tended to enter non-informative, irrelevant areas of pictures sooner than visualizers. The comparison of learning outcomes showed that the group of visualizers achieved better results than the group of verbalizers on a comprehension test.
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  • Mobasheri, Ali, et al. (author)
  • Osteoarthritis Research Society International (OARSI) : Past, present and future
  • 2021
  • In: Osteoarthritis and Cartilage Open. - : Elsevier BV. - 2665-9131. ; 3:2
  • Research review (peer-reviewed)abstract
    • We provide a detailed account of the origin and establishment of the Osteoarthritis Research Society International (OARSI) and celebrate its history from inception to the current day. We discuss the mission, vision and strategic objectives of OARSI and how these have developed and evolved over the last 3 decades. We celebrate the achievements of the society as we approach its 30th birthday, honor the entire presidential line and respectfully pay tribute to the past presidents who are no longer with us. We reflect on the strong foundations of our society, OARSI's efforts to disseminate understanding of the health, disability and economic burdens of osteoarthritis (OA) to policymakers, and the exciting initiatives to make the society inclusive and international. We thank our corporate and industrial sponsors, who have supported us over many years, without whom our annual congresses would not have been possible. We celebrate our longstanding strategic partnership with our publisher, Elsevier, and the successful launch of our new journal Osteoarthritis and Cartilage Open, the most significant new development in our dissemination toolbox. For the first time in the history of the organization, our annual congress was cancelled in April 2020 and the 2021 meeting will be virtual. Despite the numerous challenges posed by the ongoing COVID-19 pandemic and the need to adapt quickly to a rapidly changing landscape, we must remain optimistic about the future. We will take advantage of new exciting opportunities to advance our mission and vision to enhance the quality of life of persons with OA.
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  • Pleijel, Håkan, 1958, et al. (author)
  • Differential ozone sensitivity in an old and a modem Swedish wheat cultivar - grain yield and quality, leaf chlorophyll and stomatal conductance
  • 2006
  • In: Environmental and Experimental Botany. - : Elsevier BV. - 0098-8472. ; 56:1, s. 63-71
  • Journal article (peer-reviewed)abstract
    • Field-grown crops of one modem ('Dragon') and one 100-year old ('Lantvete') wheat (Triticum aestivum L.) cultivar were exposed to charcoal-filtered air (CF) or non-filtered air plus additional ozone (NF+) in open-top chambers (n = 6). Ambient air plots (11 = 3) were used to monitor the effects of the chamber enclosure. Quantitative (ear weight, harvest index and 1000-grain weight), as well as qualitative (grain concentration of N. P. K, Ca, Mg, Cd), aspects of crop yield were studied. In addition, the chlorophyll content of the top leaf was followed during the 10-week-long ozone exposure and flag leaf stomatal conductance was monitored. Ear weight was negatively affected by ozone. The effect was smaller in the lower yielding 'Lantvete' compared to the modem cultivar 'Dragon'. A similar ozone effect was found for the harvest index and 1000-grain weight. The difference between cultivars was small for 1000-grain weight, with harvest index significantly lower in 'Lantvete' compared with 'Dragon'. The crude protein concentration of the grain was higher in 'Lantvete', and was enhanced by ozone exposure. No significant treatment or cultivar effects were observed on grain Ca and Cd concentrations, but the greatest chamber effect was on Cd, which was considerably higher in grain from treatment chambers compared with ambient air (possibly due to the higher rate of transpiration in the plants enclosed in the chambers). There were strong differences with respect to grain P, K and Mg concentration between cultivars; 'Lantvete' exhibiting higher concentrations than 'Dragon' in all cases, apart from K. Weak, but significant, increases in grain P, K and Mg concentrations were evident in O-3-treated plants. The chlorophyll concentration of the flag leaf was negatively affected by ozone exposure after approximately I month, but chlorophyll content declined faster in 'Dragon' than 'Lantvete'. Flag leaf chlorophyll concentration was significantly lower in 'Lantvete' compared with 'Dragon' before onset of ozone effects in NF+ and during most of the experiment in CF. Stomatal conductance was also significantly lower in 'Lantvete' than in 'Dragon'. The most important conclusion drawn from the present study is that the 'older' cultivar, 'Lantvete', was less affected by ozone than the modem, bred cultivar, 'Dragon'. This observation might to a large extent be explained by the higher stomatal conductance exhibited by the modern wheat cultivar. The result is consistent with earlier investigations for Greek wheat cultivars, and suggests that the findings reported by others, based on vegetative growth, may extend to grain yield. Growth dilution effects (i.e. the lower observed concentration of an element at higher biomass yield) may explain observed differences between cultivars, and between ozone treatments, in the level of various elements, except for potassium. (c) 2005 Elsevier B.V. All rights reserved.
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  • Sarteau, A. C., et al. (author)
  • Changes to care delivery at nine international pediatric diabetes clinics in response to the COVID-19 global pandemic
  • 2021
  • In: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 22:3, s. 463-468
  • Journal article (peer-reviewed)abstract
    • Background Pediatric diabetes clinics around the world rapidly adapted care in response to COVID-19. We explored provider perceptions of care delivery adaptations and challenges for providers and patients across nine international pediatric diabetes clinics. Methods Providers in a quality improvement collaborative completed a questionnaire about clinic adaptations, including roles, care delivery methods, and provider and patient concerns and challenges. We employed a rapid analysis to identify main themes. Results Providers described adaptations within multiple domains of care delivery, including provider roles and workload, clinical encounter and team meeting format, care delivery platforms, self-management technology education, and patient-provider data sharing. Providers reported concerns about potential negative impacts on patients from COVID-19 and the clinical adaptations it required, including fears related to telemedicine efficacy, blood glucose and insulin pump/pen data sharing, and delayed care-seeking. Particular concern was expressed about already vulnerable patients. Simultaneously, providers reported 'silver linings' of adaptations that they perceived as having potential to inform care and self-management recommendations going forward, including time-saving clinic processes, telemedicine, lifestyle changes compelled by COVID-19, and improvements to family and clinic staff literacy around data sharing. Conclusions Providers across diverse clinical settings reported care delivery adaptations in response to COVID-19-particularly telemedicine processes-created challenges and opportunities to improve care quality and patient health. To develop quality care during COVID-19, providers emphasized the importance of generating evidence about which in-person or telemedicine processes were most beneficial for specific care scenarios, and incorporating the unique care needs of the most vulnerable patients.
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  • Sator, Lea, et al. (author)
  • Overdiagnosis of COPD in Subjects With Unobstructed Spirometry A BOLD Analysis
  • 2019
  • In: Chest. - : Elsevier BV. - 0012-3692 .- 1931-3543. ; 156:2, s. 277-288
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: There are several reports on underdiagnosis of COPD, while little is known about COPD overdiagnosis and overtreatment. We describe the overdiagnosis and the prevalence of spirometrically defined false positive COPD, as well as their relationship with overtreatment across 23 population samples in 20 countries participating in the BOLD Study between 2003 and 2012.METHODS: A false positive diagnosis of COPD was considered when participants reported a doctor's diagnosis of COPD, but postbronchodilator spirometry was unobstructed (FEV1/FVC > LLN). Additional analyses were performed using the fixed ratio criterion (FEV1/FVC < 0.7).RESULTS: Among 16,177 participants, 919 (5.7%) reported a previous medical diagnosis of COPD. Postbronchodilator spirometry was unobstructed in 569 subjects (61.9%): false positive COPD. A similar rate of overdiagnosis was seen when using the fixed ratio criterion (55.3%). In a subgroup analysis excluding participants who reported a diagnosis of "chronic bronchitis" or "emphysema" (n = 220), 37.7% had no airflow limitation. The site-specific prevalence of false positive COPD varied greatly, from 1.9% in low- to middle-income countries to 4.9% in high-income countries. In multivariate analysis, overdiagnosis was more common among women, and was associated with higher education; former and current smoking; the presence of wheeze, cough, and phlegm; and concomitant medical diagnosis of asthma or heart disease. Among the subjects with false positive COPD, 45.7% reported current use of respiratory medication. Excluding patients with reported asthma, 34.4% of those with normal spirometry still used a respiratory medication.CONCLUSIONS: False positive COPD is frequent. This might expose nonobstructed subjects to possible adverse effects of respiratory medication.
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  • Watson, Hunna J., et al. (author)
  • Common Genetic Variation and Age of Onset of Anorexia Nervosa
  • 2022
  • In: BIOLOGICAL PSYCHIATRY: GLOBAL OPEN SCIENCE. - : Elsevier BV. - 2667-1743. ; 2:4, s. 368-378
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche.METHODS: A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed, which included 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of onset, early-onset AN (,13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses.RESULTS: Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (single nucleotide polymorphism-h2) were 0.01-0.04 for age of onset, 0.16-0.25 for early-onset AN, and 0.17-0.25 for typical-onset AN. Early-and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age of onset and early-onset AN estimated from independent GWASs significantly predicted age of onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early -onset AN.CONCLUSIONS: Our results provide evidence consistent with a common variant genetic basis for age of onset and implicate biological pathways regulating menarche and reproduction.
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