| 1. |
- Swat, M. J., et al.
(författare)
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Pharmacometrics Markup Language (PharmML) : Opening New Perspectives for Model Exchange in Drug Development
- 2015
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Ingår i: CPT. - : American Society for Clinical Pharmacology & Therapeutics. - 2163-8306. ; 4:6, s. 316-319
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Tidskriftsartikel (refereegranskat)abstract
- The lack of a common exchange format for mathematical models in pharmacometrics has been a long-standing problem. Such a format has the potential to increase productivity and analysis quality, simplify the handling of complex workflows, ensure reproducibility of research, and facilitate the reuse of existing model resources. Pharmacometrics Markup Language (PharmML), currently under development by the Drug Disease Model Resources (DDMoRe) consortium, is intended to become an exchange standard in pharmacometrics by providing means to encode models, trial designs, and modeling steps.
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| 2. |
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| 3. |
- Baklanov, D. V., et al.
(författare)
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Comparison of transendocardial and retrograde coronary venous intramyocardial catheter delivery systems in healthy and infarcted pigs
- 2006
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Ingår i: Catheterization and cardiovascular interventions. - : Wiley-Blackwell. - 1522-1946 .- 1522-726X. ; 68:3, s. 416-423
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Tidskriftsartikel (refereegranskat)abstract
- We compared two routes for myocardial delivery of therapeutics, transendocardial (TE) delivery with an intramyocardial injection catheter, and retrograde coronary venous (RCV) delivery with a balloon occlusion catheter in the interventricular vein. Methods: TE and RCV injection of 15 mu m, neutron-activatable microspheres was compared in healthy pigs (Group I, n = 3), pigs with a 1-week-old myocardial infarction (MI; group II, n = 5), and pigs with a 2-weeks-old MI (group III, n = 4). The MI was induced by a 1-hr balloon occlusion in the LAD. Both methods were compared in the same animal using different microspheres. The RCV catheter allowed for continuous measurement of distal pressure and 2.5 x 10(6) microspheres were injected in 10 ml at 300 mmHg above balloon occlusion pressure. The TE injections were targeted to the infarct zone and 2.5 x 10(6) microspheres were distributed over 10 injections of 200 mu l. Results: The retention of microspheres decreased with increase in MI age, but was comparable between devices within the groups. RCV delivery resulted in (14.3 +/- 0.9)% microsphere retention in Group I, (10.3 +/- 0.2)% in Group II, and (6.4 +/- 0.1)% in group III (P less than 0.05 versus group I). Microsphere retention after TE was (15.1 +/- 0.7)% in group I, (18.9 +/- 0.6)% in group II, (4.1 +/- 0.1)% in Group III (P less than 0.05 versus groups I and II). The RCV catheter delivered primarily to midventricular, antero-septal segments, whereas TE targeted apical areas predominantly. Conclusions: Delivery efficacy was comparable between devices in each group however RCV targeted midventricular areas whereas TE targeted apical areas.
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| 4. |
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| 5. |
- Hesketh, Kylie D., et al.
(författare)
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Protocol for the Lets Grow randomised controlled trial : examining efficacy, cost-effectiveness and scalability of a m-Health intervention for movement behaviours in toddlers
- 2022
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Ingår i: BMJ Open. - : BMJ Publishing Group. - 2044-6055. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Despite being an important period for the development of movement behaviours (physical activity, sedentary behaviour and sleep), few interventions commencing prior to preschool have been trialled. The primary aim of this trial is to assess the 12-month efficacy of the Lets Grow mHealth intervention, designed to improve the composition of movement behaviours in children from 2 years of age. Lets Grow is novel in considering composition of movement behaviours as the primary outcome, using non-linear dynamical approaches for intervention delivery, and incorporating planning for real-world implementation and scale-up from its inception. Methods and analysis A randomised controlled trial will test the effects of the 12-month parental support mHealth intervention, Lets Grow, compared with a control group that will receive usual care plus electronic newsletters on unrelated topics for cohort retention. Lets Grow will be delivered via a purpose-designed mobile web application with linked SMS notifications. Intervention content includes general and movement-behaviour specific parenting advice and incorporates established behaviour change techniques. Intervention adherence will be monitored by app usage data. Data will be collected from participants using 24-hour monitoring of movement behaviours and parent report at baseline (T-0), mid-intervention (T-1; 6 months post baseline), at intervention conclusion (T-2; 12 months post baseline) and 1-year post intervention (T-3; 2 years post baseline). The trial aims to recruit 1100 families from across Australia during 2021. In addition to assessment of efficacy, an economic evaluation and prospective scalability evaluation will be conducted. Ethics and dissemination The study was approved by the Deakin University Human Ethics Committee (2020-077). Study findings will be disseminated through publication in peer-reviewed journals, presentation at scientific and professional conferences, and via social and traditional media.
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| 6. |
- Morf, Andrea, 1968, et al.
(författare)
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Challenges and Enablers to Integrate Land-Sea-Interactions in Cross-Border Marine and Coastal Planning: Experiences from the Pan Baltic Scope Collaboration
- 2022
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Ingår i: Planning Practice and Research. - : Informa UK Limited. - 0269-7459 .- 1360-0583. ; 37:3, s. 333-354
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Tidskriftsartikel (refereegranskat)abstract
- This paper analyses challenges and enablers for integrating a transboundary land-sea interaction (LSI) perspective into marine spatial planning (MSP) practice as experienced in the Baltic Sea Region. Collaborative research results from the Pan Baltic Scope project indicate that LSI remains an amorphous concept, particularly within a transboundary MSP context. Difficulty lies in bridging planning practices across land and sea and between varying uses, administrative settings and governance functions. Addressing LSI requires capacity, time, resources, awareness, reflection, and forums for collaborative learning across sectors and governance levels.
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| 7. |
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| 8. |
- Brahim, Lydia Ould, et al.
(författare)
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The effects of self-management interventions on depressive symptoms in adults with chronic physical disease(s) experiencing depressive symptomatology : a systematic review and meta-analysis
- 2021
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Ingår i: BMC Psychiatry. - : BioMed Central (BMC). - 1471-244X. ; 21:1
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Forskningsöversikt (refereegranskat)abstract
- Background Chronic diseases are the leading cause of death worldwide. It is estimated that 20% of adults with chronic physical diseases experience concomitant depression, increasing their risk of morbidity and mortality. Low intensity psychosocial interventions, such as self-management, are part of recommended treatment; however, no systematic review has evaluated the effects of depression self-management interventions for this population. The primary objective was to examine the effect of self-management interventions on reducing depressive symptomatology in adults with chronic disease(s) and co-occurring depressive symptoms. Secondary objectives were to evaluate the effect of these interventions on improving other psychosocial and physiological outcomes (e.g., anxiety, glycemic control) and to assess potential differential effect based on key participant and intervention characteristics (e.g., chronic disease, provider). Methods Studies comparing depression self-management interventions to a control group were identified through a) systematic searches of databases to June 2018 [MEDLINE (1946 -), EMBASE (1996 -), PsycINFO (1967 -), CINAHL (1984 -)] and b) secondary 'snowball' search strategies. The methodological quality of included studies was critically reviewed. Screening of all titles, abstracts, and full texts for eligibility was assessed independently by two authors. Data were extracted by one author and verified by a second. Results Fifteen studies were retained: 12 for meta-analysis and three for descriptive review. In total, these trials included 2064 participants and most commonly evaluated interventions for people with cancer (n = 7) or diabetes (n = 4). From baseline to < 6-months (T1), the pooled mean effect size was - 0.47 [95% CI -0.73, - 0.21] as compared to control groups for the primary outcome of depression and - 0.53 [95% CI -0.91, - 0.15] at >= 6-months (T2). Results were also significant for anxiety (T1) and glycemic control (T2). Self-management skills of decision-making and taking action were significant moderators of depression at T1. Conclusion Self-management interventions show promise in improving depression and anxiety in those with concomitant chronic physical disease. The findings may contribute to the development of future Self-management interventions and delivering evidence-based care to this population. Further high-quality RCTs are needed to identify sources of heterogeneity and investigate key intervention components.
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| 9. |
- Cahill, P. L., et al.
(författare)
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Creating New Antifoulants Using the Tools and Tactics of Medicinal Chemistry
- 2024
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Ingår i: Accounts of Chemical Research. - : American Chemical Society. - 0001-4842 .- 1520-4898. ; 57:3, s. 399-
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Tidskriftsartikel (refereegranskat)abstract
- Conspectus The unwanted accumulation of marine micro- and macroorganisms such as algae and barnacles on submerged man-made structures and vessel hulls is a major challenge for any marine operation. Known as biofouling, this problem leads to reduced hydrodynamic efficiency, significantly increased fuel usage, microbially induced corrosion, and, if not managed appropriately, eventual loss of both performance and structural integrity. Ship hull biofouling in the international maritime transport network conservatively accounts for 0.6% of global carbon emissions, highlighting the global scale and the importance of this problem. Improved antifouling strategies to limit surface colonization are paramount for essential activities such as shipping, aquaculture, desalination, and the marine renewable energy sector, representing both a multibillion dollar cost and a substantial practical challenge. From an ecological perspective, biofouling is a primary contributor to the global spread of invasive marine species, which has extensive implications for the marine environment. Historically, heavy metal-based toxic biocides have been used to control biofouling. However, their unwanted collateral ecological damage on nontarget species and bioaccumulation has led to recent global bans. With expanding human activities within aquaculture and offshore energy, it is both urgent and apparent that environmentally friendly surface protection remains key for maintaining the function of both moving and stationary marine structures. Biofouling communities are typically a highly complex network of both micro- and macroorganisms, representing a broad section of life from bacteria to macrophytes and animals. Given this diversity, it is unrealistic to expect that a single antifouling “silver bullet” will prevent colonization with the exception of generally toxic biocides. For that reason, modern and future antifouling solutions are anticipated to rely on novel coating technologies and “combination therapies” where mixtures of narrow-spectrum bioactive components are used to provide coverage across fouling species. In contrast to the existing cohort of outdated, toxic antifouling strategies, such as copper- and tributyltin-releasing paints, modern drug discovery techniques are increasingly being employed for the rational design of effective yet safe alternatives. The challenge for a medicinal chemistry approach is to effectively account for the large taxonomic diversity among fouling organisms combined with a lack of well-defined conserved molecular targets within most taxa. The current Account summarizes our work employing the tools of modern medicinal chemistry to discover, modify, and develop optimized and scalable antifouling solutions based on naturally occurring antifouling and repelling compounds from both marine and terrestrial sources. Inspiration for rational design comes from targeted studies on allelopathic natural products, natural repelling peptides, and secondary metabolites from sessile marine organisms with clean exteriors, which has yielded several efficient and promising antifouling leads.
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| 10. |
- Goetghebeur, Els, et al.
(författare)
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Formulating causal questions and principled statistical answers
- 2020
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Ingår i: Statistics in Medicine. - : WILEY. - 0277-6715 .- 1097-0258. ; 39:30, s. 4922-4948
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Tidskriftsartikel (refereegranskat)abstract
- Although review papers on causal inference methods are now available, there is a lack of introductory overviews onwhatthey can render and on the guiding criteria for choosing one particular method. This tutorial gives an overview in situations where an exposure of interest is set at a chosen baseline ("point exposure") and the target outcome arises at a later time point. We first phrase relevant causal questions and make a case for being specific about the possible exposure levels involved and the populations for which the question is relevant. Using the potential outcomes framework, we describe principled definitions of causal effects and of estimation approaches classified according to whether they invoke the no unmeasured confounding assumption (including outcome regression and propensity score-based methods) or an instrumental variable with added assumptions. We mainly focus on continuous outcomes and causal average treatment effects. We discuss interpretation, challenges, and potential pitfalls and illustrate application using a "simulation learner," that mimics the effect of various breastfeeding interventions on a child's later development. This involves a typical simulation component with generated exposure, covariate, and outcome data inspired by a randomized intervention study. The simulation learner further generates various (linked) exposure types with a set of possible values per observation unit, from which observed as well as potential outcome data are generated. It thus provides true values of several causal effects. R code for data generation and analysis is available on , where SAS and Stata code for analysis is also provided.
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| 11. |
- Holopainen, Päivi, et al.
(författare)
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Candidate gene region 2q33 in European families with coeliac disease.
- 2004
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Ingår i: Tissue antigens. - : Wiley. - 0001-2815 .- 1399-0039. ; 63:3, s. 212-22
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Tidskriftsartikel (refereegranskat)abstract
- Chromosome region 2q33 harbours a cluster of genes, CTLA-4, CD28, ICOS and closely located PD-1, all related to immune activation and considered as promising candidate genes for susceptibility to coeliac disease (CD). We present here the results of a genetic linkage and association analysis of nine markers located in this gene region in a large combined European material of 796 families with CD from Finland, Sweden, Norway, UK, France and Italy. The joint analysis supports earlier findings that this susceptibility locus, assigned as CELIAC3, merits further studies. Nominally significant linkage to CD was found in 314 families including affected sib pairs. Each of the five populations showed weak associations to several marker alleles, but the analysis revealed, however, no conclusive evidence for a primary functional gene or gene variant present in the total set of families. The results suggest that the CD risk due to 2q33 gene region is complex and may involve more than one susceptibility allele, which possibly differ from other autoimmune diseases.
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| 12. |
- Mandinov, L., et al.
(författare)
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Inhibition of in-stent restenosis by oral copper chelation in porcine coronary arteries
- 2006
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Ingår i: American Journal of Physiology. Heart and Circulatory Physiology. - : American Physiological Society. - 0363-6135 .- 1522-1539. ; 291:6, s. H2692-H2697
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Tidskriftsartikel (refereegranskat)abstract
- Stress-induced release of IL-1 alpha and fibroblast growth factor-1 is dependent on intracellular copper and is a major driver of neointimal hyperplasia. Therefore, we assessed the effect of tetrathiomolybdate (TTM), a clinically proven copper chelator, on in-stent restenosis. Nine pigs were treated with TTM (5 mg/kg po) twice daily for 2 wk before stent implantation and for 4 wk thereafter, and nine pigs served as controls. In-stent restenosis was assessed by quantitative coronary angiography (QCA), intravascular ultrasound (IVUS), and histomorphometry. Serum ceruloplasmin activity was used as a surrogate marker of copper bioavailability. In TTM-treated animals, ceruloplasmin dropped 70 +/- 10% below baseline levels. Baseline characteristics were comparable in TTM-treated and control animals. At 4-wk follow-up, all parameters relevant to in-stent restenosis were significantly reduced in TTM-treated animals: minimal lumen diameter by QCA was 2.03 +/- 0.57 and 1.47 +/- 0.45 mm in TTM-treated and control animals, respectively (P less than 0.05), percent stenosis diameter was 39% less in TTM-treated animals (27.1 +/- 16.6% vs. 44.5 +/- 16.1%, P less than 0.05), minimal lumen area by IVUS was 60% larger in TTM-treated animals (4.27 +/- 1.56 vs. 2.67 +/- 1.19 mm(2), P less than 0.05), and neointimal volume by histomorphometry was 37% less in TTM-treated animals (34.9 +/- 11.5 vs. 55.2 +/- 19.6 mm(3), P less than 0.05). We conclude that systemic copper chelation with a clinically approved chelator significantly inhibits in-stent restenosis.
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| 13. |
- Moodie, Katherine F., et al.
(författare)
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The Relationship of Ultrasound Measurements of Muscle Deformation With Torque and Electromyography During Isometric Contractions of the Cervical Extensor Muscles
- 2020
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Ingår i: Journal of Manipulative and Physiological Therapeutics. - : MOSBY-ELSEVIER. - 0161-4754 .- 1532-6586. ; 43:4, s. 284-293
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Speckle tracking analysis (STA) of ultrasound (US) images quantifies the longitudinal deformation of a region of muscle tissue to provide a mechanical measure of muscle activity. As the validity and reliability of this method has not yet been adequately assessed, the aim of this study was to determine the validity and reliability of STA in the dorsal neck muscles during isometric neck extension contractions. Methods: Twenty volunteers performed 3 repetitions of isometric neck extension in a dynamometer at 10%, 20%, 40%, 60%, and 80% of maximal voluntary torque while US and surface electromyography (EMG) data were recorded. Speckle tracking analysis was then used to calculate measurements of muscle deformation. The relationship among torque, muscle deformation (separate for each muscle and summed), and EMG was evaluated using linear regressions and Spearmans correlation coefficients. The reliability of EMG and muscle deformation was determined using intraclass correlation coefficients (ICCs). Results: Muscle deformation in 4 of the 5 muscles when examined separately and collectively was significantly related to torque (P < .05); however, the relationship was weak (r(2) = 0.03-0.18). In contrast, a strong linear relationship was observed between torque and EMG (P < .001, r(2) = 0.83). Poor to moderate reliability of muscle deformation measures (ICC: 0.02-0.69) was found compared with EMG, which was highly reliable (ICC: 0.67-0.90). Conclusion: These results suggest that the validity of US STA measurements for isometric contractions of the dorsal neck muscles is questionable. Further investigation into this method is required before it can be used as a tool to measure muscle activity.
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| 14. |
- Morf, Andrea, 1968, et al.
(författare)
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Towards sustainability of marine governance: Challenges and enablers for stakeholder integration in transboundary marine spatial planning in the Baltic Sea
- 2019
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Ingår i: Ocean & Coastal Management. - : Elsevier BV. - 0964-5691. ; 177, s. 200-212
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Tidskriftsartikel (refereegranskat)abstract
- Integrating stakeholder knowledge, views and needs in marine or maritime spatial planning (MSP) processes is important from a governance and social sustainability perspective both for MSP practitioners and for the evolving field of MSP research. Transboundary MSP appears particularly challenging for participation, which is why it is important to identify opportunities and address obstacles for stakeholder integration in this specific context. This article examines how stakeholder integration is currently practiced in the Baltic Sea Region (BSR), an enclosed sea where policy coherence and addressing conflicting interests across borders are especially relevant. It synthesises a range of challenges and enablers for stakeholder participation and mobilisation that have emerged from two transboundary MSP research and development projects, BaltSpace and Baltic SCOPE. The article finds that with the exception of statutory authorities, stakeholder engagement in the BSR is mostly limited to self-motivated stakeholders and consultation rather than more inclusive forms of participation. This can reduce the quality and legitimacy of MSP processes and risks to concentrate power in the hands of a small group of actors. For transboundary stakeholder integration to become more interactive and effective, five types of challenges need attention, regarding a) timing, b) governance systems, c) capacity and processes, d) stakeholder characteristics and e) knowledge and language. These obstacles can be addressed by (1) a dedicated research and development agenda that critically reflects on integrative tools and processes, and (2) by encouraging transnational institutions in the BSR to devote more resources to transboundary stakeholder integration and adopt flexible and adaptive strategies and tools that can facilitate stakeholder involvement throughout the MSP policy cycle.
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| 15. |
- Petersen, Solveig, et al.
(författare)
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Relationship between overweight and health-related quality of life in secondary school children in Fiji : results from a cross-sectional population-based study
- 2014
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Ingår i: International Journal of Obesity. - : Nature Publishing Group. - 0307-0565 .- 1476-5497. ; 38:4, s. 539-546
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the relationship between excess weight (overweight and obesity) and health-related quality of life (HRQoL) in a sample of secondary school children in Fiji, by gender, age and ethnicity.Methods: The study comprised 8947 children from forms 3-6 (age 12-18 years) in 18 secondary schools on Viti Levu, the main island of Fiji. Body mass index (BMI) was calculated from measured height and weight, and weight status was classified according to the International Obesity Task Force recommendations. HRQoL was measured by the self-report version of the Pediatric Quality of Life Inventory 4.0.Results: HRQoL was similar in children with obesity and normal weight. Generally, this was replicated when analyzed separately by gender and ethnicity, but age stratification revealed disparities. In 12-14-year-old children, obesity was associated with better HRQoL, owing to better social and school functioning and well-being, and in 15-18-year olds with poorer HRQoL, owing to worse physical, emotional and social functioning and well-being (Cohen's d 0.2-0.3). Children with a BMI in the overweight range also reported a slightly lower HRQoL than children with a BMI in the normal weight range, but although statistically significant, the size of this difference was trivial (Cohen's d <0.2).Discussion: The results suggest that, overall there is no meaningful negative association between excess weight and HRQoL in secondary school children in Fiji. This is in contradiction to the negative relationship between excess weight and HRQoL shown in studies from other countries and cultures. The assumption that a large body size is associated with a lower quality of life cannot be held universally. Although a generally low HRQoL among children in Fiji may be masking or overriding the potential effect of excess weight on HRQoL, socio-economic and/or socio-cultural factors, may help to explain these relationships.
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| 16. |
- Rodrigues, Leticia, et al.
(författare)
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Cellular uptake of self-assembled phytantriol-based hexosomes is independent of major endocytic machineries
- 2019
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier. - 0021-9797 .- 1095-7103. ; 553, s. 820-833
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Tidskriftsartikel (refereegranskat)abstract
- Despite increasing interests in non-lamellar liquid crystalline dispersions, such as hexosomes, for drug delivery, little is known about their interactions with cells and mechanism of cell entry. Here we examine the cellular uptake of hexosomes based on phytantriol and mannide monooleate by HeLa cells using live cell microscopy in comparison to conventional liposomes. To investigate the importance of specific endocytosis pathways upon particle internalization, we silenced regulatory proteins of major endocytosis pathways using short interfering RNA. While endocytosis plays a significant role in liposome internalization, hexosomes are not taken up via endocytosis but through a mechanism that is dependent on cell membrane tension. Biophysical studies using biomembrane models highlighted that hexosomes have a high affinity for membranes and an ability to disrupt lipid layers. Our data suggest that direct biomechanical interactions of hexosomes with membrane lipids play a crucial role and that the unique morphology of hexosomes is vital for their membrane activity. Based on these results, we propose a mechanism, where hexosomes destabilize the bilayer, allowing them to "phase through" the membrane. Understanding parameters that influence the uptake of hexosomes is critical to establish them as carrier systems that can potentially deliver therapeutics efficiently to intracellular sites of action.
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