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1.
  • Simonsson, Christian, et al. (author)
  • A uni fi ed framework for prediction of liver steatosis dynamics in response to different diet and drug interventions
  • 2024
  • In: Clinical Nutrition. - : CHURCHILL LIVINGSTONE. - 0261-5614 .- 1532-1983. ; 43:6, s. 1532-1543
  • Journal article (peer-reviewed)abstract
    • Background & aims: Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder, characterized by the accumulation of excess fat in the liver, and is a driving factor for various severe liver diseases. These multi -factorial and multi-timescale changes are observed in different clinical studies, but these studies have not been integrated into a uni fied framework. In this study, we aim to present such a uni fied framework in the form of a dynamic mathematical model. Methods: For model training and validation, we collected data for dietary or drug -induced interventions aimed at reducing or increasing liver fat. The model was formulated using ordinary differential equations (ODEs) and the mathematical analysis, model simulation, model formulation and the model parameter estimation were all performed in MATLAB. Results: Our mathematical model describes accumulation of fat in the liver and predicts changes in lipid fluxes induced by both dietary and drug interventions. The model is validated using data from a wide range of drug and dietary intervention studies and can predict both short-term (days) and long-term (weeks) changes in liver fat. Importantly, the model computes the contribution of each individual lipid flux to the total liver fat dynamics. Furthermore, the model can be combined with an established bodyweight model, to simulate even longer scenarios (years), also including the effects of insulin resistance and body weight. To help prepare for corresponding eHealth applications, we also present a way to visualize the simulated changes, using dynamically changing lipid droplets, seen in images of liver biopsies. Conclusion: In conclusion, we believe that the minimal model presented herein might be a useful tool for future applications, and to further integrate and understand data regarding changes in dietary and drug induced changes in ectopic TAG in the liver. With further development and validation, the minimal model could be used as a disease progression model for steatosis. (c) 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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2.
  • Herrgårdh, Tilda, et al. (author)
  • A multi-scale digital twin for adiposity-driven insulin resistance in humans : diet and drug effects
  • 2023
  • In: Diabetology & Metabolic Syndrome. - : BioMed Central (BMC). - 1758-5996. ; 15:1
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The increased prevalence of insulin resistance is one of the major health risks in society today. Insulin resistance involves both short-term dynamics, such as altered meal responses, and long-term dynamics, such as the development of type 2 diabetes. Insulin resistance also occurs on different physiological levels, ranging from disease phenotypes to organ-organ communication and intracellular signaling. To better understand the progression of insulin resistance, an analysis method is needed that can combine different timescales and physiological levels. One such method is digital twins, consisting of combined mechanistic mathematical models. We have previously developed a model for short-term glucose homeostasis and intracellular insulin signaling, and there exist long-term weight regulation models. Herein, we combine these models into a first interconnected digital twin for the progression of insulin resistance in humans.METHODS: The model is based on ordinary differential equations representing biochemical and physiological processes, in which unknown parameters were fitted to data using a MATLAB toolbox. RESULTS: The interconnected twin correctly predicts independent data from a weight increase study, both for weight-changes, fasting plasma insulin and glucose levels, and intracellular insulin signaling. Similarly, the model can predict independent weight-change data in a weight loss study with the weight loss drug topiramate. The model can also predict non-measured variables.CONCLUSIONS: The model presented herein constitutes the basis for a new digital twin technology, which in the future could be used to aid medical pedagogy and increase motivation and compliance and thus aid in the prevention and treatment of insulin resistance.
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3.
  • Ling, Charlotte, et al. (author)
  • Genetic and epigenetic factors are associated with expression of respiratory chain component NDUFB6 in human skeletal muscle.
  • 2007
  • In: The Journal of clinical investigation. - 0021-9738. ; 117:11, s. 3427-35
  • Journal article (peer-reviewed)abstract
    • Insulin resistance and type 2 diabetes are associated with decreased expression of genes that regulate oxidative phosphorylation in skeletal muscle. To determine whether this defect might be inherited or acquired, we investigated the association of genetic, epigenetic, and nongenetic factors with expression of NDUFB6, a component of the respiratory chain that is decreased in muscle from diabetic patients. Expression of NDUFB6 was influenced by age, with lower gene expression in muscle of elderly subjects. Heritability of NDUFB6 expression in muscle was estimated to be approximately 60% in twins. A polymorphism in the NDUFB6 promoter region that creates a possible DNA methylation site (rs629566, A/G) was associated with a decline in muscle NDUFB6 expression with age. Although young subjects with the rs629566 G/G genotype exhibited higher muscle NDUFB6 expression, this genotype was associated with reduced expression in elderly subjects. This was subsequently explained by the finding of increased DNA methylation in the promoter of elderly, but not young, subjects carrying the rs629566 G/G genotype. Furthermore, the degree of DNA methylation correlated negatively with muscle NDUFB6 expression, which in turn was associated with insulin sensitivity. Our results demonstrate that genetic, epigenetic, and nongenetic factors associate with NDUFB6 expression in human muscle and suggest that genetic and epigenetic factors may interact to increase age-dependent susceptibility to insulin resistance.
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4.
  • Silfvergren, Oscar, et al. (author)
  • Digital twin predicting diet response before and after long-term fasting
  • 2022
  • In: PloS Computational Biology. - : Public Library of Science. - 1553-734X .- 1553-7358. ; 18:9
  • Journal article (peer-reviewed)abstract
    • Today, there is great interest in diets proposing new combinations of macronutrient compositions and fasting schedules. Unfortunately, there is little consensus regarding the impact of these different diets, since available studies measure different sets of variables in different populations, thus only providing partial, non-connected insights. We lack an approach for integrating all such partial insights into a useful and interconnected big picture. Herein, we present such an integrating tool. The tool uses a novel mathematical model that describes mechanisms regulating diet response and fasting metabolic fluxes, both for organ-organ crosstalk, and inside the liver. The tool can mechanistically explain and integrate data from several clinical studies, and correctly predict new independent data, including data from a new study. Using this model, we can predict non-measured variables, e.g. hepatic glycogen and gluconeogenesis, in response to fasting and different diets. Furthermore, we exemplify how such metabolic responses can be successfully adapted to a specific individuals sex, weight, height, as well as to the individuals historical data on metabolite dynamics. This tool enables an offline digital twin technology.
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5.
  • Simonsson, Charlotta, et al. (author)
  • Classic Psychedelic Use and Current Meditation Practice
  • 2023
  • In: Mindfulness. - : SPRINGER. - 1868-8527 .- 1868-8535. ; 14, s. 763-768
  • Journal article (peer-reviewed)abstract
    • ObjectivesPrevious research has investigated potential synergies between classic psychedelics and meditation practice, but relatively little remains known about the relationship between classic psychedelic experiences and engagement with meditation practice. The purpose of this study was to investigate associations between classic psychedelic experiences and engagement with two popular types of meditation: mindfulness meditation and loving-kindness or compassion meditation.MethodThis retrospective, population-based observational study included 2822 respondents aged 18 years or older in the United States. Using covariate-adjusted regression models, this study examined associations of classic psychedelic experiences with current practice of mindfulness meditation and loving-kindness or compassion meditation.ResultsIn covariate-adjusted regression models, lifetime classic psychedelic use was associated with a higher frequency of current mindfulness meditation practice but not current loving-kindness or compassion meditation practice. Both psychological insight and "ego dissolution" were associated with a higher frequency of current mindfulness meditation practice and current loving-kindness or compassion meditation practice. Notably, when psychological insight and "ego dissolution" were entered into the regression model simultaneously, only greater psychological insight was associated with having a higher frequency of current mindfulness meditation practice and current loving-kindness or compassion meditation practice.ConclusionsAlthough the findings in this study cannot demonstrate causality, they suggest that classic psychedelic experiences may exert a positive effect on the cultivation and maintenance of health-related behaviors such as regular meditation practice, with psychological insight appearing to be a stronger predictor than "ego dissolution."PreregistrationThis study was not preregistered.
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6.
  • Simonsson, Kjell, et al. (author)
  • Kamratutvärdering i kurser med stort datorlaborativt inslag
  • 2014
  • Reports (other academic/artistic)abstract
    • De mångfacetterade krav som idag ställs på yrkesverksamma högskole- och civilingenjörer handlar inte enbart om rena ämnesmässiga kunskaper och förmågor, utan även om t.ex. erfarenhet och förmåga att delta i och leda projekt samt (kopplat till detta) kommunikativ skicklighet (såväl muntlig som skriftlig). En annan uppgift som yrkesverksamma ingenjörer måste kunna bemästra i sin profession är att (individuellt, eller som medlemmar i olika typer av styrgrupper) bedöma och utvärdera andras ingenjörsmässiga arbete, en oerhört central uppgift i ett projekt- och kvalitetssäkringsperspektiv.Det övergripande syftet med arbetet har varit att studera hur kamratbedömning kan implementeras i redan existerande kurser, för att på så sätt ge de studerande möjlighet att träna på att ge och ta emot kritisk bedömning, att förbättra de studerandes lärande via ett större aktivt engagemang under kursen samt att se om potential finns att effektivisera undervisningen m.a.p. lärarinsatsen, genom att lyfta över en del av enklare rutinkontroller till de studerande själva.Kamratbedömning har implementerats i två sinsemellan likartade kurser inom beräkningsmekanik vid högskole- resp. civilingenjörsprogrammen i Maskinteknik, LiTH (600 studenter ingick i studien). Mer specifikt har till två enklare inledande laborationsuppgifter inkluderats ett moment av kamratbedömning. Utvärderingen av det genomförda arbetet har skett via en kvalitativ studie, där de studerandes perspektiv/synpunkter inhämtats i samband med skriftlig redovisning av inlämningsuppgifter. Utöver detta har den kursansvarige gjort observationer av hur kamratutvärderingsarbetet fortskridit under laborationstid.Resultatet visar att de studerande har uppskattat granskningen av såväl det egna som kamraternas arbeten, och att de sett det som ett led i lärandeprocessen. Även professionsperspektivet har lyfts fram där de studerande betonar vikten av moment och uppgifter i utbildningen som har en direkt relevans i det kommande yrkeslivet. Den kursansvariges bedömning är vidare att andelen ”viktiga” och ”relevanta” frågor ökat, vilket ger indikationer på att kamratbedömning kan vara en såväl pedagogiskt som effektivitetsmässigt gynnsam metodik. De studerande har dock upplevt logistiken/administrationen kring kamratvärderingen som i vissa avseenden besvärlig.Sammanfattningsvis är det vår slutsats att kamratbedömning har en stor potential att berika utbildningar m.a.p. förmåga till kritisk granskning, djupinlärning och effektivisering, men att verksamheten inte bara skall implementeras kursvis (med risk för suboptimering och ineffektivitet), utan att den bör inlemmas i ett större perspektiv, med progression genom utbildningen som riktmärke.
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7.
  • Simonsson, Otto, et al. (author)
  • Psychedelic use and psychiatric risks
  • 2023
  • In: Psychopharmacology. - : SPRINGER. - 0033-3158 .- 1432-2072.
  • Journal article (peer-reviewed)abstract
    • RationaleResearch on psychedelics has recently shown promising results in the treatment of various psychiatric disorders, but relatively little remains known about the psychiatric risks associated with naturalistic use of psychedelics.ObjectiveThe objective of the current study was to investigate associations between naturalistic psychedelic use and psychiatric risks.MethodsUsing a sample representative of the US adult population with regard to sex, age, and ethnicity (N=2822), this study investigated associations between lifetime naturalistic psychedelic use, lifetime unusual visual experiences, and past 2-week psychotic symptoms.ResultsAmong respondents who reported lifetime psychedelic use (n=613), 1.3% reported having been told by a doctor or other medical professional that they had hallucinogen persisting perception disorder. In covariate-adjusted linear regression models, lifetime psychedelic use was associated with more unusual visual experiences at any point across the lifetime, but no association was observed between lifetime psychedelic use and past 2-week psychotic symptoms. There was an interaction between lifetime psychedelic use and family (but not personal) history of psychotic or bipolar disorders on past 2-week psychotic symptoms such that psychotic symptoms were highest among respondents who reported lifetime psychedelic use and a family history of psychotic or bipolar disorders and lowest among those who reported lifetime psychedelic use and no family history of psychotic or bipolar disorders.ConclusionsAlthough the results in this study should be interpreted with caution, the findings suggest that lifetime naturalistic use of psychedelics might be associated with more unusual visual experiences across the lifetime, as well as more psychotic symptoms in the past 2 weeks for individuals with a family history of psychotic or bipolar disorders and the reverse for those without such a family history. Future research should distinguish between different psychotic and bipolar disorders and should also utilize other research designs (e.g., longitudinal) and variables (e.g., polygenic risk scores) to better understand potential cause-and-effect relationships.
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8.
  • Simonsson, Peter (author)
  • Buildability of concrete structures : processes, methods and material
  • 2011
  • Doctoral thesis (other academic/artistic)abstract
    • The causes for the slow development of the construction industry is often attributed the traditional ”peculiarities of construction“, including such factors as one-of-a-kind products, temporary organisation, and on-site production. However, signs of new thinking are becoming apparent in the construction industry in Sweden that emphasise change. Globalization and increased competition are factors for change. The possible future shortage of available qualified workers, demand for shorter construction times and calculated higher risks for projects are also catalysers for the implementation of new and alternative solutions. Still, new production methods and construction ideas are rarely introduced in construction projects, with low or no productivity increase of the industry as a result. Within the scope of this thesis work, the combination of creating buildability during the design phase and utilizing the philosophies of lean construction during the construction phase has been adapted to improve civil engineering concrete construction work. Several full scale projects have been studied and a questionnaire survey has been performed. In order to be able to introduce changes such as prefabricated reinforcement solutions, left concrete form systems and Self-Compacting Concrete (SCC) as a mean to increase productivity at site, there is a need to create projects that are buildable and able to be constructed, i.e. constructions that we know in advance are practically feasible and productive. All involved participants throughout the whole project are therefore responsible for creating buildability in the project. The case studies show that the potential increase in productivity can be vast. The introduction of prefabricated rebar sections, e.g. rebar carpets and rebar cages, decreases time spent on fixing reinforcement with up to 80%. The use of SCC potentially saves 65% on time spent during casting. Both methods improve the working environment substantially. However, the introduction of new methods also put demands on properly planned, communicated and managed construction operations on-site. Thus, the use of Buildability in the design can promote new solutions together with Lean Construction philosophies in management of these alternatives are suitable tools in changing the construction industry. Buildability deals with creating design for “ease of construction” whilst Lean construction focus on planning of a productive flow of work tasks and resources for the selected production methods. The combination of buildability in the “design for” part and lean construction philosophy in the “ease of construction” part within one of the most accepted definitions of buildability i.e. “the extent to which the design of a building facilitates ease of construction” will be able to encourage an increase in productivity at construction sites. This is possible if important factors are considered and utilised sufficiently. Some of these important factors highlighted in this thesis work are: • early project involvement of contractor, to increase construction knowledge during design, a result from the questionnaire survey; • design projects in 3D and create adequate virtual work instructions for workers to study prior to performing the work task, a result from full scale studies; • plan the construction work tasks and material supply thoroughly using lean tools, a result from full scale studies; • make sure adequate attention is spent on the working environment early in a project, this will result in workers feeling confident in a safe work environment, a result from full scale studies. The thesis corroborates the conclusion that, if these factors are considered and encouraged there is a potential for improvement of productivity at site, enhanced quality of finished structures as well as lowered costs for constructing structures in the future.
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9.
  • Venturi, Giorgia, et al. (author)
  • Strengthening old steel railway bridges: a review
  • 2021
  • In: IABSE Congress Ghent 2021. - Zurich, Switzerland : International Association for Bridge and Structural Engineering (IABSE). ; , s. 1718-1727
  • Conference paper (peer-reviewed)abstract
    • Strengthening old bridges is an increasingly relevant strategy for risk prevention and operation continuity in management of infrastructures. Transportation networks are subjected to progressively stricter environmental and load conditions, leading to a growing number of deficient structures, also due to aging and deterioration. However, employable resources are finite, from both economical and environmental points of view. For these reasons, strengthening opportunities should be considered as a viable option, improving bridges behaviour with low economical and environmental impact. With this perspective, a selection of some of the most interesting strengthening techniques for old truss railway bridges is presented. To address effective solutions, the most frequent problems in old truss railway bridges are first presented. Literature analysis and experts’ interviews were conducted and compared to results obtained from a representative bridge cluster. Different solutions addressing highlighted problems are then collected and qualitatively evaluated, in terms of efficacy on structural behaviour and typical construction requirements. Finally, general remarks and recommendations based on collected evidence are presented.
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10.
  • Widlund, Hans R., et al. (author)
  • Identification and characterization of genomic nucleosome-positioning sequences
  • 1997
  • In: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836. ; 267, s. 807-817
  • Journal article (peer-reviewed)abstract
    • Positioned nucleosomes are believed to play important roles in transcriptional regulation and for the organization of chromatin in cell nuclei. Here, we have isolated the DNA segments in the mouse genome that form the most stable nucleosomes yet characterized. In separate molecules we find phased runs of three to four adenine nucleotides, extensive CA repeats, and in a few cases phased TATA tetranucleotides. The latter forms the most stable nucleosome yet characterized. One sequence with CAG repeats was also found. By fluorescence in situ hydridization the selected sequences are shown to be localized at the centromeric regions of mouse metaphase chromosomes.
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11.
  • Zvada, Simbarashe P., et al. (author)
  • Population pharmacokinetics of rifampicin, pyrazinamide and isoniazid in children with tuberculosis : in silico evaluation of currently recommended doses
  • 2014
  • In: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 69:5, s. 1339-1349
  • Journal article (peer-reviewed)abstract
    • To describe the population pharmacokinetics of rifampicin, pyrazinamide and isoniazid in children and evaluate the adequacy of steady-state exposures. We used previously published data for 76 South African children with tuberculosis to describe the population pharmacokinetics of rifampicin, pyrazinamide and isoniazid. Monte Carlo simulations were used to predict steady-state exposures in children following doses in fixed-dose combination tablets in accordance with the revised guidelines. Reference exposures were derived from an ethnically similar adult population with tuberculosis taking currently recommended doses. The final models included allometric scaling of clearance and volume of distribution using body weight. Maturation was included for clearance of isoniazid and clearance and absorption transit time of rifampicin. For a 2-year-old child weighing 12.5 kg, the estimated typical oral clearances of rifampicin and pyrazinamide were 8.15 and 1.08 L/h, respectively. Isoniazid typical oral clearance (adjusted for bioavailability) was predicted to be 4.44, 11.6 and 14.6 L/h for slow, intermediate and fast acetylators, respectively. Higher oral clearance values in intermediate and fast acetylators also resulted from 23 lower bioavailability compared with slow acetylators. Simulations based on our models suggest that with the new WHO dosing guidelines and utilizing available paediatric fixed-dose combinations, children will receive adequate rifampicin exposures when compared with adults, but with a larger degree of variability. However, pyrazinamide and isoniazid exposures in many children will be lower than in adults. Further studies are needed to confirm these findings in children administered the revised dosages and to optimize pragmatic approaches to dosing.
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12.
  • Ahrén, Bo, et al. (author)
  • Inhibition of dipeptidyl peptidase IV improves metabolic control over a 4-week study period in type 2 diabetes.
  • 2002
  • In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 25:5, s. 869-75
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: Glucagon-like peptide-1 (GLP-1) has been proposed as a new treatment modality for type 2 diabetes. To circumvent the drawback of the short half-life of GLP-1, inhibitors of the GLP-1-degrading enzyme dipeptidyl peptidase IV (DPP IV) have been examined. Such inhibitors improve glucose tolerance in insulin-resistant rats and mice. In this study, we examined the 4-week effect of 1-[[[2-[(5-cyanopyridin-2-yl)amino]ethyl]amino]acetyl]-2-cyano-(S)-pyrrolidine (NVP DPP728), a selective, orally active inhibitor of DPP IV, in subjects with diet-controlled type 2 diabetes in a placebo-controlled double-blind multicenter study.RESEARCH DESIGN AND METHODS: A total of 93 patients (61 men and 32 women), aged 64 +/- 9 years (means +/- SD) and with BMI 27.3 +/- 2.7 kg/m(2), entered the study. Fasting blood glucose was 8.5 +/- 1.5 mmol/l, and HbA(1c) was 7.4 +/- 0.7%. Before and after treatment with NVP DPP728 at 100 mg x 3 (n = 31) or 150 mg x 5 (n = 32) or placebo (n = 30), subjects underwent a 24-h study with standardized meals (total 2,000 kcal).RESULTS: Compared with placebo, NVP DPP728 at 100 mg t.i.d. reduced fasting glucose by 1.0 mmol/l (mean), prandial glucose excursions by 1.2 mmol/l, and mean 24-h glucose levels by 1.0 mmol/l (all P < 0.001). Similar reductions were seen in the 150-mg b.i.d. treatment group. Mean 24-h insulin was reduced by 26 pmol/l in both groups (P = 0.017 and P = 0.023). Although not an efficacy parameter foreseen in the study protocol, HbA(1c) was reduced to 6.9 +/- 0.7% in the combined active treatment groups (P < 0.001). Laboratory safety and tolerability was good in all groups.CONCLUSIONS: We conclude that inhibition of DPP IV is a feasible approach to the treatment of type 2 diabetes in the early stage of the disease.
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13.
  • Andersson, Håkan, et al. (author)
  • A co-simulation method for system-level simulation of fluid-structure couplings in hydraulic percussion units
  • 2017
  • In: Engineering with Computers. - : SPRINGER. - 0177-0667 .- 1435-5663. ; 33:2, s. 317-333
  • Journal article (peer-reviewed)abstract
    • This paper addresses a co-simulation method for fluid power driven machinery equipment, i.e. oil hydraulic machinery. In these types of machinery, the fluid-structure interaction affects the end-product performance to a large extent, hence an efficient co-simulation method is of high importance. The proposed method is based on a 1D system model representing the fluid components of the hydraulic machinery, within which structural 3D Finite Element (FE) models can be incorporated for detailed simulation of specific sub-models or complete structural assemblies. This means that the fluid system simulation will get a more accurate structural response, and that the structural simulation will get more correct fluid loads at every time step, compared to decoupled analysis. Global system parameters such as fluid flow, performance and efficiency can be evaluated from the 1D system model simulation results. From the 3D FE-models, it is possible to evaluate displacements, stresses and strains to be used in stress analysis, fatigue evaluation, acoustic analysis, etc. The method has been implemented using two well-known simulation tools for fluid power system simulations and FE-simulations, respectively, where the interface between the tools is realised by use of the Functional Mock-up Interface standard. A simple but relevant model is used to validate the method.
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15.
  • Asp, Margareta, professor, 1958-, et al. (author)
  • Physical mobility, physical activity, and obesity among elderly : findings from a large population-based Swedish survey
  • 2017
  • In: Public Health. - : Elsevier B.V.. - 0033-3506 .- 1476-5616. ; 147, s. 84-91
  • Journal article (peer-reviewed)abstract
    • Objective To examine how physical activity and physical mobility are related to obesity in the elderly. Study design A cross-sectional study of 2558 men and women aged 65 years and older who participated in a population survey in 2012 was conducted in mid-Sweden with an overall response rate of 67%. Methods Obesity (body mass index ≥30 kg/m2) was based on self-reported weight and height, and physical activity and physical mobility on questionnaire data. Chi-squared test and multiple logistic regressions were used as statistical analyses. Results The overall prevalence of obesity was 19% in women and 15% in men and decreased after the age of 75 years. A strong association between both physical activity and obesity, and physical mobility and obesity was found. The odds for obesity were higher for impaired physical mobility (odds ratio [OR] 2.83, 95% confidence interval [CI] 2.14–3.75) than for physical inactivity (OR 1.63, 95% CI 1.28–2.08) when adjusted for gender, age, socio-economic status and fruit and vegetable intake. However, physical activity was associated with obesity only among elderly with physical mobility but not among those with impaired physical mobility. Conclusion It is important to focus on making it easier for elderly with physical mobility to become or stay physically active, whereas elderly with impaired physical mobility have a higher prevalence of obesity irrespective of physical activity.
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17.
  • Björk, Mårten, et al. (author)
  • Vilka av de döpta är kristna? [bloggpost]
  • 2021
  • Other publication (pop. science, debate, etc.)abstract
    • Ingress: Sedan länge har risken för förföljelse på grund av religion varit påtaglig för kristna asylsökande här i landet. Inte framförallt risken att förföljas i Sverige, om än den inte är obefintlig, utan risken att utvisas till ett land där ens trostillhörighet riskerar en trakasserier, hot, våld och i värsta fall död. Hur skall då svenska domstolar hantera påståenden om att en asylsökande är kristen och risken att denne förföljs vid resa till ursprungslandet? Särskilt tillspetsad blir frågan då någon konverterar under vistelsen i Sverige. Skall den svenska rättsordningen ta sådana konvertiter på allvar? Föreligger inte risken att den nya tron bara är en taktisk manöver för att förstärka ens asylskäl?
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18.
  • Björnfot, Anders, et al. (author)
  • 'Find-think-write-publish' : Lean thinking in scientific paper writing
  • 2012
  • Conference paper (peer-reviewed)abstract
    • Construction research supports long-term development of the construction industry and the society. Thus it is important to evaluate research against existing knowledge and to constantly develop new knowledge. The main mechanism for doing so is publishing scientific papers. In Sweden, praxis has developed that a Ph.D. consists of a handful of scientific papers. The average time period for a Ph.D. is five years after which the funding situation changes drastically. Previously, the duration of Ph.D. studies at Luleå University of Technology, Sweden often exceeded the planned five years, disrupting the flow of Ph.D. examinations. To increase awareness and interest in paper writing, a method was sought to visualise and manage the writing process. This paper investigates how an Oobeya room can be implemented in construction research to support paper writing. Experiences of working with the Oobeya room in three separate research divisions prove that it is possible and fruitful to better manage knowledge in academic institutions. Even though research is creative, it can be properly managed without hampering scientific freedom. Evidence from managing scientific paper writing using the Oobeya room shows that proper management of research will actually create better research that is more publishable with shorter lead times!.
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19.
  • Björnfot, Anders, et al. (author)
  • Lessons learned from successful value stream mapping (VSM)
  • 2011
  • In: Proceedings of IGLC-19. - Lima : Fondo Ed. Pontificia Universidad Católica del Peru. - 9781622768233 ; , s. 163-173
  • Conference paper (other academic/artistic)abstract
    • To improve, it’s crucial to see! Vital characteristics of Lean are visualisation and transparency, i.e. allowing everyone to see all what occurs in production. A common tool for this purpose is Value Stream Mapping (VSM). Due to varying flows, performing a successful VSM in construction confers additional challenges. In this paper, lessons learned from successful VSM studies in construction are provided.Three VSM case studies were performed at different companies ranging from patio door manufacturing to kitchen cabinet assembly. Lessons learned can be structured into three phases; preparing the VSM (selecting “value stream leaders” and VSM team, clarifying values, etc.), performing the VSM (use of mapping tools, approximation of key indicators, waste identification, etc.), and following-up the VSM (Plan-Do-Check-Act, evaluating customer values, etc.).For the involved companies, the lessons learned imply the start of a “Lean journey” even though the involved companies found it difficult to relate VSM improvements to business strategies. Consequently, there are opportunities to further improve the application of VSM. However, it’s important to remember that VSM is about the straight-forward visualisation of flows and that these flows are made transparent for the whole organisation.
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20.
  • Borgmästars, Emmy, et al. (author)
  • Improved Detection of Norovirus and Hepatitis A Virus in Surface Water by Applying Pre-PCR Processing
  • 2017
  • In: Food and Environmental Virology. - : Springer Science and Business Media LLC. - 1867-0334 .- 1867-0342. ; 9:4, s. 395-405
  • Journal article (peer-reviewed)abstract
    • Quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) detection of waterborne RNA viruses generally requires concentration of large water volumes due to low virus levels. A common approach is to use dead-end ultrafiltration followed by precipitation with polyethylene glycol. However, this procedure often leads to the co-concentration of PCR inhibitors that impairs the limit of detection and causes false-negative results. Here, we applied the concept of pre-PCR processing to optimize RT-qPCR detection of norovirus genogroup I (GI), genogroup II (GII), and hepatitis A virus (HAV) in challenging water matrices. The RT-qPCR assay was improved by screening for an inhibitor-tolerant master mix and modifying the primers with twisted intercalating nucleic acid molecules. Additionally, a modified protocol based on chaotropic lysis buffer and magnetic silica bead nucleic acid extraction was developed for complex water matrices. A validation of the modified extraction protocol on surface and drinking waters was performed. At least a 26-fold improvement was seen in the most complex surface water studied. The modified protocol resulted in average recoveries of 33, 13, 8, and 4% for mengovirus, norovirus GI, GII, and HAV, respectively. The modified protocol also improved the limit of detection for norovirus GI and HAV. RT-qPCR inhibition with Cq shifts of 1.6, 2.8, and 3.5 for norovirus GI, GII, and HAV, respectively, obtained for the standard nucleic acid extraction were completely eliminated by the modified protocol. The standard nucleic acid extraction method worked well on drinking water with no RT-qPCR inhibition observed and average recoveries of 80, 124, 89, and 32% for mengovirus, norovirus GI, GII, and HAV, respectively.
  •  
21.
  • Bäckström, Erik, 1983-, et al. (author)
  • Storing keV negative ions for an hour : The lifetime of the metastable 2P1/2 level in 32S−
  • 2015
  • In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 114:14
  • Journal article (peer-reviewed)abstract
    • We use a novel electrostatic ion storage ring to measure the radiative lifetime of the upper level in the 3p 5  P 2  o 1/2 →3p 5  P 2  o 3/2   spontaneous radiative decay in S −  32   to be 503±54  sec . This is by orders of magnitude the longest lifetime ever measured in a negatively charged ion. Cryogenic cooling of the storage ring gives a residual-gas pressure of a few times 10 −14   mbar at 13 K and storage of 10 keV sulfur anions for more than an hour. Our experimental results differ by 1.3σ  from the only available theoretical prediction.
  •  
22.
  • Chartkunchand, Kiattichart C., et al. (author)
  • Dianion diagnostics in DESIREE : High-sensitivity detection of C-n(2-) from a sputter ion source
  • 2018
  • In: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 89:3
  • Journal article (peer-reviewed)abstract
    • A sputter ion source with a solid graphite target has been used to produce dianions with a focus on carbon cluster dianions, C-n(2-), with n = 7-24. Singly and doubly charged anions from the source were accelerated together to kinetic energies of 10 keV per atomic unit of charge and injected into one of the cryogenic (13 K) ion-beam storage rings of the Double ElectroStatic Ion Ring Experiment facility at Stockholm University. Spontaneous decay of internally hot C-n(2-) dianions injected into the ring yielded C-n(2-) anions with kinetic energies of 20 keV, which were counted with a microchannel plate detector. Mass spectra produced by scanning the magnetic field of a 90 degrees analyzing magnet on the ion injection line reflect the production of internally hot C-7(2-) - C-24(2-) dianions with lifetimes in the range of tens of microseconds to milliseconds. In spite of the high sensitivity of this method, no conclusive evidence of C-6(2-) was found while there was a clear C-7(2-) signal with the expected isotopic distribution. This is consistent with earlier experimental studies and with theoretical predictions. An upper limit is deduced for a C-6(2-) signal that is two orders-of-magnitude smaller than that for C-7(2-). In addition, CnO2- and CnCu2- dianions were detected.
  •  
23.
  • Chartkunchand, Kiattichart C., et al. (author)
  • Radiative lifetimes of the bound excited states of Pt-
  • 2016
  • In: Physical Review A - Atomic, Molecular, and Optical Physics. - 1050-2947 .- 1094-1622. ; 94:3
  • Journal article (peer-reviewed)abstract
    • © 2016 American Physical Society.The intrinsic radiative lifetimes of the 5d106sS1/22 and 5d96s2 D3/22 bound excited states in the platinum anion Pt- have been studied at cryogenic temperatures at the Double ElectroStatic Ion Ring Experiment (DESIREE) facility at Stockholm University. The intrinsic lifetime of the higher-lying 5d106s S1/22 state was measured to be 2.54±0.10s, while only a lifetime in the range of 50-200 ms could be estimated for the 5d96s2 D3/22 fine-structure level. The storage lifetime of the Pt- ion beam was measured to be a little over 15 min at a ring temperature of 13K. The present study reports the lifetime of an atomic negative ion in an excited bound state with an electron configuration different from that of the ground state.
  •  
24.
  •  
25.
  • Eklund, Gustav, et al. (author)
  • Cryogenic merged-ion-beam experiments in DESIREE : Final-state-resolved mutual neutralization of Li+ and D-
  • 2020
  • In: Physical Review A: covering atomic, molecular, and optical physics and quantum information. - : American Physical Society (APS). - 2469-9926 .- 2469-9934. ; 102:1
  • Journal article (peer-reviewed)abstract
    • We have developed an experimental technique to study charge-and energy-flow processes in sub-eV collisions between oppositely charged, internally cold, ions of atoms, molecules, and clusters. Two ion beams are stored in separate rings of the cryogenic ion-beam storage facility DESIREE, and merged in a common straight section where a set of biased drift tubes is used to control the center-of-mass collision energy locally in fine steps. Here, we present measurements on mutual neutralization between Li+ and D- where a time-sensitive imaging-detector system is used to measure the three-dimensional distance between the neutral Li and D atoms as they reach the detector. This scheme allows for direct measurements of kinetic-energy releases, and here it reveals separate populations of the 3s state and the (3p + 3d) states in neutral Li while the D atom is left in its ground state 1s. The branching fraction of the 3s final state is measured to be 57.8 +/- 0.7% at a center-of-mass collision energy of 78 +/- 13 meV. The technique paves the way for studies of charge-, energy-, and mass-transfer reactions in single collisions involving molecular and cluster ions in well-defined quantum states.
  •  
26.
  •  
27.
  • Ekström, Daniel P T, 1976, et al. (author)
  • Climate impact optimization in concrete bridge construction
  • 2017
  • In: IABSE Conference, Vancouver 2017. - : International Association for Bridge and Structural Engineering (IABSE). - 9783857481536 ; , s. 1161-1168, s. 1161-1168
  • Conference paper (peer-reviewed)abstract
    • Estimates indicate that the total climate impact, from a lifecycle perspective, generated by Swedish construction processes reaches the same magnitude as emissions from all passenger cars in Sweden. A large part of the emissions from construction of roads and railways arise from production of steel and concrete used in bridges and other infrastructure structures. In this research, several cases of existing concrete bridges have been investigated. The case studies are in a very firm way analyzed, and then opportunities for reducing climate gas emissions are described and elaborated upon. Accordingly, design and dimensioning through the use of today's technology and material selection are discussed. Without developing new ways to construct bridges, or comparing concrete with other materials, a useful guide on how to use technology and opportunities that are available for constructing climate smarter versions of standard bridges today is developed and described.
  •  
28.
  • Ekström, Daniel P T, 1976, et al. (author)
  • Integrated project teams in early design stages - Key variables influencing cost effectiveness in bridge building
  • 2016
  • In: 19th IABSE Congress Stockholm, 21-23 September 2016, Challenges in Design and Construction of an Innovative and Sustainable Built Environment. ; , s. 598-606
  • Conference paper (peer-reviewed)abstract
    • The construction industry is usually regarded as a complex, multidisciplinary and project focused environment. It is also regularly identified as a one-of-a-kind nature, hence focus is on the uniqueness of projects rather than in similarities. The results presented in this article are based on questionnaire addressed to clients, contractors, and designers, mainly active within the Swedish infrastructure sector. The purpose is to highlight key-variables influencing cost effectiveness for the organization of integrated project teams, designing of projects, and construction at site. The results indicate that more attention needs to be paid to the actual project setting if to fully gain the benefits from integrated project teams. Further, the results indicates that it is mainly project culture; collaboration and social relationships, and project competence, the ability to solve mutual issues, that needs to be developed.
  •  
29.
  • Elsherbiny, Doaa, et al. (author)
  • Population pharmacokinetics of nevirapine in combination with rifampicin-based short course chemotherapy in HIV- and tuberculosis-infected South African patients
  • 2009
  • In: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 65:1, s. 71-80
  • Journal article (peer-reviewed)abstract
    • The aim was to develop a model to describe the population pharmacokinetics of nevirapine in South African human immunodeficiency virus (HIV)-infected patients who were taking nevirapine-based antiretroviral therapy concomitantly or in the absence of rifampicin-based tuberculosis therapy. Patients were divided into two groups: (1) patients receiving   nevirapine-containing antiretroviral regimen (200 mg twice daily) and continuation phase rifampicin-containing tuberculosis therapy (n = 27) in whom blood samples were obtained before and not less than 14 days after they completed tuberculosis therapy; (2) patients without tuberculosis who were receiving a nevirapine-containing antiretroviral regimen for at least 3 weeks (n = 26). The population pharmacokinetics of nevirapine was described using nonlinear mixed effects modelling   with NONMEM software. Based on the developed model, plasma concentration profiles after 300, 400 and 500 mg of nevirapine twice daily were simulated. Concomitant administration of rifampicin increased nevirapine oral clearance (CL/F) by 37.4% and reduced the absorption rate constant (k(a)) by almost sixfold. Rifampicin reduced the nevirapine average minimum concentration by 39%. Simulated doses of 300 mg twice daily elevated nevirapine concentrations above subtherapeutic levels in most patients, with minimum exposure above the recommended maximum concentration. The area under the concentration-time curve of 12-hydroxynevirapine was not different in the presence of rifampicin. 2-, 3- and 8-Hydroxynevirapine were not detectable (LLOQ = 0.025 mg/L). The developed model adequately describes nevirapine population   pharmacokinetics in a South African population when taken with/and in the absence of rifampicin treatment. The simulations suggest that an increased dose of 300 mg twice daily would achieve adequate nevirapine concentrations in most patients during rifampicin-containing treatment for tuberculosis.
  •  
30.
  • Emborg, Mats, et al. (author)
  • Designing robust SCC for industrial construction with cast in place concrete
  • 2005
  • In: Second North American Conference on the Design and Use of Self-Consolidating Concrete [and] Fourth International RILEM Symposium on Self-Compacting Concrete; [October 30 - November 2, 2005];Second North American Conference on the Design and Use of Self-Consolidating Concrete [and] Fourth International RILEM Symposium on Self-Compacting Concrete; [October 30 - November 2, 2005. - Hanley Wood. ; , s. 1251-1257
  • Conference paper (peer-reviewed)
  •  
31.
  • Emborg, Mats, et al. (author)
  • Increasing the market share of SCC
  • 2010
  • In: Concrete Plant International. - 1437-9023. ; :3, s. 218-222
  • Journal article (other academic/artistic)
  •  
32.
  •  
33.
  •  
34.
  • Emborg, Mats, et al. (author)
  • Industrial concrete construction for a better economy and working environment : possibilities and obstacles with self compacting concrete
  • 2008
  • In: Nordic Concrete Research. - 0800-6377. ; :2, s. 47-59
  • Journal article (peer-reviewed)abstract
    • The implementation of SCC together with new reinforcement and form techniques make it possible to increase the degree of industrialisation. It has been found in research at LTU that detailed planning and optimization of the building process, are essential utensils to successfully introduce such new techniques. However, also important is to address the technical issues hindering the marketing of SCC. Such issues are the robustness of the concrete and he surface quality. Thus, a discussion is given in the article on the optimization of robust SCC mixes and test results both from laboratory and building site as well as how criteria of SCC can be defined.
  •  
35.
  • Fischer, D., et al. (author)
  • Importance of Thomas single-electron transfer in fast p-He collisions
  • 2010
  • In: Physical Review A. Atomic, Molecular, and Optical Physics. - 1050-2947 .- 1094-1622. ; 81:1, s. 12714-
  • Journal article (peer-reviewed)abstract
    • We report experimental angular differential cross sections for nonradiative single-electron capture in p-He collisions (p + He -> H + He+) with a separate peak at the 0.47 mrad Thomas scattering angle for energies in the 1.3-12.5 MeV range. We find that the intensity of this peak scales with the projectile velocity as v(P)(-11). This constitutes the first experimental test of the prediction from 1927 by L. H. Thomas [Proc. R. Soc. 114, 561 (1927)]. At our highest energy, the peak at the Thomas angle contributes with 13.5% to the total integrated nonradiative single-electron capture cross section.
  •  
36.
  • Furuskär, Anders, et al. (author)
  • Controlling QoS for Mixed Voice and Data Services in GERAN - The GSM/EDGE Radio Access Network
  • 2001
  • In: Proceedings - 2001 International Conference on Third Generation Wireless and Beyond. - New York : IEEE. - 0780367286 ; , s. 147-151
  • Conference paper (peer-reviewed)abstract
    • This paper describes and evaluates service-based power setting for the GSM/EDGE Radio Access Network (GERAN). Service-based power setting is a simple radio resource management scheme that allows management of multiple services with controlled quality of service (QoS), which is crucial for 3rd generation systems. Simulation results indicate that with proper power offsets between bearer services previously established single service capacities may be maintained also for a mix of different services. It is further shown that the power setting principles work well in combination with power control.
  •  
37.
  • Furuskär, Anders, et al. (author)
  • Managing Mixed Services with Controlled QoS in GERAN - The GSM/EDGE Radio Access Network
  • 2001
  • In: 3G Mobile Communication Technologies, 2001. Second International Conference on (Conf. Publ. No. 477). - New York : IEEE. - 0852967314 ; , s. 147-151
  • Conference paper (peer-reviewed)abstract
    • Managing multiple services with controlled quality of service (QoS) is crucial to 3rd generation cellular systems. This paper describes and evaluates a simple radio resource management scheme; service-based power setting, employed to accomplish this goal for the GSM/EDGF radio access network (GERAN). Simulation results indicate that with proper power offsets between bearer services previously established high capacities for single services may be maintained also for a mix of different services with controlled QoS.
  •  
38.
  • Furuskär, Anders, et al. (author)
  • Mixed Service Management with QoS Control for GERAN - The GSM/EDGE Radio Access Network
  • 2001
  • In: IEEE Vehicular Technology Conference. - New York : IEEE. - 0780367286 ; , s. 2635-2639
  • Conference paper (peer-reviewed)abstract
    • This paper describes and evaluates service-based power setting for the GSM/EDGE Radio Access Network (GERAN). Service-based power setting is a simple radio resource management scheme that allows management of multiple services with controlled Quality of Service (QoS), which is crucial for 3rd generation systems. Simulation results indicate that with proper power offsets between bearer services previously established single service capacities may be maintained also for a mix of different services. It is further shown that the power setting principles work well in combination with power control.
  •  
39.
  • Gatchell, Michael, et al. (author)
  • Commissioning of the DESIREE storage rings - a new facility for cold ion-ion collisions
  • 2014
  • In: XXVIII International Conference on Photonic, Electronic and Atomic Collisions (ICPEAC 2013). - : Institute of Physics (IOP). ; 488:1
  • Conference paper (peer-reviewed)abstract
    • We report on the ongoing commissioning of the Double ElectroStatic Ion Ring ExpEriment, DESIREE, at Stockholm University. Beams of atomic carbon anions (C-) and smaller carbon anion molecules (C-2(-), C-3(-), C-4(-) etc.) have been produced in a sputter ion source, accelerated to 10 keV or 20 keV, and stored successfully in the two electrostatic rings. The rings are enclosed in a common vacuum chamber cooled to below 13 Kelvin. The DESIREE facility allows for studies of internally relaxed single isolated atomic, molecular and cluster ions and for collision experiments between cat-and anions down to very low center-of-mass collision energies (meV scale). The total thermal load of the vacuum chamber at this temperature is measured to be 32 W. The decay rates of stored ion beams have two components: a non-exponential component caused by the space charge of the beam itself which dominates at early times and an exponential term from the neutralization of the beam in collisions with residual gas at later times. The residual gas limited storage lifetime of carbon anions in the symmetric ring is over seven minutes while the 1/e lifetime in the asymmetric ring is measured to be about 30 seconds. Although we aim to improve the storage in the second ring, the number of stored ions are now sufficient for many merged beams experiments with positive and negative ions requiring milliseconds to seconds ion storage.
  •  
40.
  • Gatchell, Michael, et al. (author)
  • First results from the Double ElectroStatic Ion-Ring ExpEriment, DESIREE
  • 2014
  • In: XXVIII International Conference on Photonic, Electronic and Atomic Collisions (ICPEAC 2013). - : Institute of Physics (IOP). ; 488
  • Conference paper (peer-reviewed)abstract
    • We have stored the first beams in one of the rings of the double electrostatic ion-storage ring, DESIREE at cryogenic and at room temperature conditions. At cryogenic operations the following parameters are found. Temperature; T= 13K, pressure; p <10(-13) mbar, initial number of stored ions; N > 10(7) and storage lifetime of a C-2(-) beam; tau = 450 S.
  •  
41.
  • Gatchell, Michael, 1988-, et al. (author)
  • Stability of C59 Knockout Fragments from Femtoseconds to Infinity
  • Other publication (other academic/artistic)abstract
    • We have studied the stability of C59 anions as a function of time, from their formation on femtosecond timescales to their stabilization on second timescales and beyond, using a combination of theory and experiments. The C59 fragments were produced in collisions between C60 fullerene anions and neutral helium gas at a velocity of 90 km/s (corresponding to a collision energy of 166 eV in the center-of-mass frame). The fragments were then stored in a cryogenic ion-beam storage ring at the DESIREE facility where they were followed for up to one minute. Classical molecular dynamics simulations were used to determine the reaction cross section and the excitation energy distributions of the products formed in these collisions. We found that about 15 percent of the C59 ions initially stored in the ring are intact after about 100 ms, and that this population then remains intact indefinitely. This means that C60 fullerenes exposed to energetic atoms and ions, such as stellar winds and shock waves, will produce stable, highly reactive products, like C59, that are fed into interstellar chemical reaction networks.
  •  
42.
  • Gatchell, Michael, 1988-, et al. (author)
  • Stability of C59 Knockout Fragments from Femtoseconds to Infinity
  • 2024
  • In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 966:2
  • Journal article (peer-reviewed)abstract
    • We have studied the stability of C59 anions as a function of time, from their formation on femtosecond timescales to their stabilization on second timescales and beyond, using a combination of theory and experiments. The C-59 fragments were produced in collisions between C60 fullerene anions and neutral helium gas at a velocity of 90 km s−1 (corresponding to a collision energy of 166 eV in the center-of-mass frame). The fragments were then stored in a cryogenic ion beam storage ring at the DESIREE facility, where they were followed for up to 1 minute. Classical molecular dynamics simulations were used to determine the reaction cross section and the excitation energy distributions of the products formed in these collisions. We find that about 15% of the C-59 ions initially stored in the ring are intact after about 100 ms and that this population then remains intact indefinitely. This means that C60 fullerenes exposed to energetic atoms and ions, such as stellar winds and shock waves, will produce stable, highly reactive products, like C59, that are fed into interstellar chemical reaction networks.
  •  
43.
  • Ghosheh, Nidal, et al. (author)
  • Comparative transcriptomics of hepatic differentiation of human pluripotent stem cells and adult human liver tissue
  • 2017
  • In: Physiological Genomics. - : American Physiological Society. - 1094-8341 .- 1531-2267. ; 49:8, s. 430-446
  • Journal article (peer-reviewed)abstract
    • Hepatocytes derived from human pluripotent stem cells (hPSC-HEP) have the potential to replace presently used hepatocyte sources applied in liver disease treatment and models of drug discovery and development. Established hepatocyte differentiation protocols are effective and generate hepatocytes, which recapitulate some key features of their in vivo counterparts. However, generating mature hPSC-HEP remains a challenge. In this study, we applied transcriptomics to investigate the progress of in vitro hepatic differentiation of hPSCs at the developmental stages, definitive endoderm, hepatoblasts, early hPSC-HEP, and mature hPSC-HEP, to identify functional targets that enhance efficient hepatocyte differentiation. Using functional annotation, pathway and protein interaction network analyses, we observed the grouping of differentially expressed genes in specific clusters representing typical developmental stages of hepatic differentiation. In addition, we identified hub proteins and modules that were involved in the cell cycle process at early differentiation stages. We also identified hub proteins that differed in expression levels between hPSC-HEP and the liver tissue controls. Moreover, we identified a module of genes that were expressed at higher levels in the liver tissue samples than in the hPSC-HEP. Considering that hub proteins and modules generally are essential and have important roles in the protein-protein interactions, further investigation of these genes and their regulators may contribute to a better understanding of the differentiation process. This may suggest novel target pathways and molecules for improvement of hPSC-HEP functionality, having the potential to finally bring this technology to a wider use.
  •  
44.
  • Ghosheh, Nidal, et al. (author)
  • Highly Synchronized Expression of Lineage-Specific Genes during In Vitro Hepatic Differentiation of Human Pluripotent Stem Cell Lines
  • 2016
  • In: Stem Cells International. - : Hindawi Limited. - 1687-966X .- 1687-9678.
  • Journal article (peer-reviewed)abstract
    • Human pluripotent stem cells- (hPSCs-) derived hepatocytes have the potential to replace many hepatic models in drug discovery and provide a cell source for regenerative medicine applications. However, the generation of fully functional hPSC-derived hepatocytes is still a challenge. Towards gaining better understanding of the differentiation and maturation process, we employed a standardized protocol to differentiate six hPSC lines into hepatocytes and investigated the synchronicity of the hPSC lines by applying RT-qPCR to assess the expression of lineage-specific genes (OCT4, NANOG, T, SOX17, CXCR4, CER1, HHEX, TBX3, PROX1, HNF6, AFP, HNF4a, KRT18, ALB, AAT, and CYP3A4) which serve as markers for different stages during liver development. The data was evaluated using correlation and clustering analysis, demonstrating that the expression of these markers is highly synchronized and correlated well across all cell lines. The analysis also revealed a distribution of the markers in groups reflecting the developmental stages of hepatocytes. Functional analysis of the differentiated cells further confirmed their hepatic phenotype. Taken together, these results demonstrate, on the molecular level, the highly synchronized differentiation pattern across multiple hPSC lines. Moreover, this study provides additional understanding for future efforts to improve the functionality of hPSC-derived hepatocytes and thereby increase the value of related models.
  •  
45.
  • Ghosheh, Nidal, 1975-, et al. (author)
  • Human Pluripotent Stem Cell-Derived Hepatocytes Show Higher Transcriptional Correlation with Adult Liver Tissue than with Fetal Liver Tissue
  • 2020
  • In: ACS Omega. - : American Chemical Society (ACS). - 2470-1343. ; 5:10, s. 4816-4827
  • Journal article (peer-reviewed)abstract
    • Human pluripotent stem cell-derived hepatocytes (hPSC-HEP) display many properties of mature hepatocytes, including expression of important genes of the drug metabolizing machinery, glycogen storage, and production of multiple serum proteins. To this date, hPSC-HEP do not, however, fully recapitulate the complete functionality of in vivo mature hepatocytes. In this study, we applied versatile bioinformatic algorithms, including functional annotation and pathway enrichment analyses, transcription factor binding-site enrichment, and similarity and correlation analyses, to datasets collected from different stages during hPSC-HEP differentiation and compared these to developmental stages and tissues from fetal and adult human liver. Our results demonstrate a high level of similarity between the in vitro differentiation of hPSC-HEP and in vivo hepatogenesis. Importantly, the transcriptional correlation of hPSC-HEP with adult liver (AL) tissues was higher than with fetal liver (FL) tissues (0.83 and 0.70, respectively). Functional data revealed mature features of hPSC-HEP including cytochrome P450 enzymes activities and albumin secretion. Moreover, hPSC-HEP showed expression of many genes involved in drug absorption, distribution, metabolism, and excretion. Despite the high similarities observed, we identified differences of specific pathways and regulatory players by analyzing the gene expression between hPSC-HEP and AL. These findings will aid future intervention and improvement of in vitro hepatocyte differentiation protocol in order to generate hepatocytes displaying the complete functionality of mature hepatocytes. Finally, on the transcriptional level, our results show stronger correlation and higher similarity of hPSC-HEP to AL than to FL. In addition, potential targets for further functional improvement of hPSC-HEP were also identified. 
  •  
46.
  • Gill, Peter Edward, 1949-, et al. (author)
  • Consequences for prevention strategies of reduced prevalence of bullying at school-class and school level in a Swedish Municipality
  • 2017
  • In: ECER 2017.
  • Conference paper (peer-reviewed)abstract
    • A crucial feature of school classes, as intact social entities, is that members share certain values (Boehnke & Schiefer, 2016). Saarento, Garandeau and Salmivalli (2015), argue that the influence of classroom- and school-level factors on bullying involves demographic, structural, peer contextual and teacher-related dimensions. Swearer et al. (2014) use a theory of “homophily and bullying” to argue for a homophily hypothesis where within group similarity leads to bullies physically or relationally rejecting those who are different and withdrawing any social support for victims.  However, Saarento, Garandeau and Salmivalli’s conclusion (op.cit.) was that the contributions of demographic, school structural and school-class characteristics remain inconsistent.  On the other hand, recent Swedish research (Thornberg et al., 2015 & Thornberg et al., 2016), after controlling for factors such as age, gender, ethnicity, school-class size and gender composition, found that relational climate and experience of moral disengagement within school-classes was a significant predictor of between-class variation in victimisation.  Victimisation was less likely in classes characterised by supportive relational patterns and lower levels of moral disengagement in the classroom, a result confirmed by Grundherr (et al., 2016). The research reported here builds on a presentation at ECER 2016 (Gill, Larsson, Matton, Simonsson & Levin, 2016) that explored some consequences of systematic reductions of prevalence of bullying at school. It was argued that Swedish anti-bullying programs are being delivered at the later phases of an implementation research continuum (Chalamandaris &  Piette, 2015).   Uncovering new or persistent cases of bullying becomes more difficult as prevalence of bullying reduces (successful implementation). Being bullied at least 2 to 3 times a month between 2009–2015, among 200,000 children in 1500 Finnish schools (grades 1–9) decreased from 17.2% at baseline to 12.6% after six years of implementation of the KiVa program (Herkama & Salmivalli, 2016). Even though creating reliable measures of bullying prevalence is difficult (Vivolo-Kantor et al., 2014), Finnish prevalence is considerably higher than in Sweden, national average is about 7/8%, which in turn, is higher than the average in the municipality where this research has been carried out (4.9%, Spring 2016).  With prevalence rates at this level it is possible to envisage realistic “zero-vision” and “zero-tolerance” strategies. (For a critical review of zero-tolerance, see Borgwald & Theixos, 2013 and James & Freeze, 2006). Any goal of reducing a low prevalence of bullying in Sweden, even lower, is mediated by the discovery, from individual-level, longitudinal data, where successful cases of ceased victims are regularly replaced by new victims (Flygare, Gill & Johansson, 2013: Hellstedt, Johansson & Gill, 2016), revealing a cyclical replacement of victims. While up to 75% of victims at one time will self-report not being victimized at one-year follow-up, rates at cross-sectional measurement may remain the same (typically 7/8% in Swedish schools, op.cit.).  The Norwegian “Zero Program” (Strohmeier and Noam, 2012) is based on a “zero-vision” manifesto. Köhler (2006) in outlining health indicators for Swedish children argues that while some ideal zero-outcomes might not stand up as credible operational targets, using “zero vision” as a reference point may be reasonable in some cases. In the municipality that is the focus here, evidence is emerging that some schools and school classes are coming closer to a zero-vision reference point.  In a school with 200 children, in 8 or 9 classes, a point prevalence rate of 3% would indicate that at least two, possibly three classes in that school had no victims of bullying.  It is argued that this circumstance creates new challenges for prevention strategies.  Therefore, it is important to delve deeper into changes in “the picture of bullying”.  That is the goal of this research.MethodSince the initiation of the rolling intervention (2011/12), where participation was voluntary, 6 schools have become 29 (including independent academy schools).  Since Autumn 2016, all 4th to 9th graders, in these schools, have participated in the municipality’s web-based “School Care Questionnaire”.  Included in this questionnaire is the instrument used by the National Agency for Education in estimating prevalence of bullying (see Flygare, Gill & Johansson, 2013, for details).  The questionnaire is delivered twice during the school year (October and April).  These measurements will allow for follow-up comparisons for 6000 children distributed between 300 school classes in 29 schools. Descriptive statistics will be used to establish realistic estimates of prevalence of bullying victimization. Rates for individuals categorised as “bullied” will be matched by a global index of “no involvement” (that is, no self-reported “incidents” of any kind, including events we refer to as “fun-like rough and tumble).Expected OutcomesFluctuations in point prevalence estimates, at classroom level, will be revealed.  These will be examined with reference to indicated cases (school classes) where bullying is recurring (at follow-up) or is seen to be exceptionally high.  Statistical patterns will be tested against practitioners, responsible teachers, head-teachers, schools anti-bullying teams and municipal supervisor’s hands-on experiences of the school year in question (2016/17).
  •  
47.
  • Gill, Peter Edward, 1949-, et al. (author)
  • Research to Practice : Rolling Implementation of Evidence-Based Anti-Bullying Strategies in a Swedish Municipality
  • 2016
  • Conference paper (peer-reviewed)abstract
    • There is a dearth of research into the consequences of systematic reductions of prevalence of target behaviors, such as bullying, in school-based prevention science.  Reducing prevalence may also result in making bullying more difficult to uncover (Cunningham et al., 2015). Preventing bullying at school is a much researched field (Ttofi & Farrington, 2011).  In international comparisons, prevalence of bullying at school varies widely, with rates for Swedish schools regularly being lowest (e.g., among 66 countries, Due & Holstein, 2008).  Conditions influencing program efficacy are likely to vary as prevalence of target behavior is reducing.  School-wide prevention strategies, in schools with one or more victims in every class, present a very different challenge compared to schools where victims are found in every second of third class.  Recent longitudinal data from Sweden (Swedish Agency for Education, 2011; Hellstedt, Johansson & Gill, 2016 forthcoming) has revealed a cyclical replacement of victims, after successful intervention, showing that while rates at cross-sectional measurement intervals may remain the same (typically 6/7% in Swedish schools), up to 75% of victims at one time will self-report not being victimized at one-year follow-up (op.cit.).  Low rates of bullying in Sweden are the result intervention strategies based on a wide variety of ‘standard’ (International, Scandinavian & National) prevention programs, at least 21 according to Skolverket (2003).  A national evaluation revealed extensive program cross-contamination, proving the unviability of “gold standard” evaluation practices. “What works” conclusions were described in terms of program components.  When “promising” evidence for effective program components is produced, there is an inevitable momentum to package components into replicable “programs”.  We argue that this momentum may hamper response flexibility, particularly when program providers, in seeking to be “evidence based” may place more importance on implementation functions such as program fidelity and dosage rather than individual outcomes. We argue that considerations such as dosage and program fidelity are less relevant when anti-bullying initiatives are being adapted to variations in school contexts and climates (Gregory, Henry & Schoeny, 2007).  Component efficacy and effectiveness may also be masked by confidentiality requirements in program evaluations and outcome assessments that are based on follow-up, cross-sectional, cohort statistics.  What works in Sweden, for example, found by Frisén, Hasselblad & Holmqvist (2012), based on evidence from former victims, in descending order of importance: Support from school personnel; Transition to new school level; Change of coping strategies; Support from parents; Change of appearance or way of being; Change of school or class as a deliberate attempt to make the bullying stop; New friends; The bullies changed their attitude; No particular reason; and Support from peers, may not translate to other cultures, school systems and traditions.  With observed low prevalence, extensive program implementation, research evidence on effective components and extensive judicial obligations, it is likely, that in most Swedish municipalities, active anti-bullying programs may, theoretically, be located at the later phases of an implementation research continuum (Chalamandaris &  Piette, 2015, after Flay,1986, & Flay et al., 2005).  This, late stage program/component developemt, also has an impact on schools’ potential capacity to improve (Oterkiil & Ertesvåg, 2012).  Given these contexts, it is important to research the present state of evidence based anti-bullying strategies in Sweden.  Using best practice in program implementation evaluation a descriptive case study of scaled-up, school district-wide (Rhoades, Bumbarger & Moore 2012), research-to-action (Guhn et al., 2012) anti-bullying strategies in a Swedish municipality is presented. The goal is to investigate conditions, participants, hindrances, responses and outcomes at different stages of a rolling implementation process.  This Swedish example may be of value in other European school systems where prevalence is reducing toward Swedish levels.
  •  
48.
  • Grimberg, Julia, et al. (author)
  • Få, fler, alla måste göra mer tillsammans : En färdplan mot ett totalt försvar
  • Other publication (pop. science, debate, etc.)abstract
    • Den svenska säkerhets- och försvarspolitiken kom snabbt att förändras under 2014 efter att Ryssland först ockuperat och sedan annekterat Krimhalvön. Sveriges verklighetsbild förändrades på några få månader, från det att Sveriges statsminister på Folk och Försvarskonferensen i Sälen i januari 2014 sagt att det var svårt att kunna tänka sig att det fanns något avgörande militära hot mot något europeiskt land. För något mer än sju år sedan, den 10 december 2015, beslutade regeringen om en återupptagen totalförsvarsplanering.Det är inom ramen för denna planering, och den svenska förmågeökning som den syftar till, som våra tankar här riktar sig till. Vi är långt ifrån klara i Sverige. Vi har precis kommit igång. Stora tankar behöver tänkas. Effekt behöver levereras.Vår uppgift är att lista utmaningar och problem i Sveriges säkerhets- och försvarspolitik inom den pågående totalförsvarsreformen och identifiera utvecklingsbehov inom svensk policy och strategi. Vi ska utmana status quo, vara framåtlutade och argumentera för de reformer som vi anser behövs.Våra slutsatser återfinns inom tre kapitelDemokratin, rättsstaten och de grundläggande fri- och rättigheterna är Sveriges främsta skyddsvärden.Ett starkt totalförsvar utifrån helhet, enkelhet och effekt.En vassare förmåga.
  •  
49.
  • Grossmann, Igor, et al. (author)
  • Insights into the accuracy of social scientists' forecasts of societal change
  • 2023
  • In: Nature Human Behaviour. - : Springer Nature. - 2397-3374. ; 7, s. 484-501
  • Journal article (peer-reviewed)abstract
    • How well can social scientists predict societal change, and what processes underlie their predictions? To answer these questions, we ran two forecasting tournaments testing the accuracy of predictions of societal change in domains commonly studied in the social sciences: ideological preferences, political polarization, life satisfaction, sentiment on social media, and gender-career and racial bias. After we provided them with historical trend data on the relevant domain, social scientists submitted pre-registered monthly forecasts for a year (Tournament 1; N = 86 teams and 359 forecasts), with an opportunity to update forecasts on the basis of new data six months later (Tournament 2; N = 120 teams and 546 forecasts). Benchmarking forecasting accuracy revealed that social scientists' forecasts were on average no more accurate than those of simple statistical models (historical means, random walks or linear regressions) or the aggregate forecasts of a sample from the general public (N = 802). However, scientists were more accurate if they had scientific expertise in a prediction domain, were interdisciplinary, used simpler models and based predictions on prior data. How accurate are social scientists in predicting societal change, and what processes underlie their predictions? Grossmann et al. report the findings of two forecasting tournaments. Social scientists' forecasts were on average no more accurate than those of simple statistical models.
  •  
50.
  • Hartman, Henrik, et al. (author)
  • First storage of ion beams in the Double Electrostatic Ion-Ring Experiment : DESIREE
  • 2013
  • In: Review of Scientific Instruments. - : American Institute of Physics (AIP). - 0034-6748 .- 1089-7623. ; 84:5
  • Journal article (peer-reviewed)abstract
    • We report on the first storage of ion beams in the Double ElectroStatic Ion Ring ExpEriment, DESIREE, at Stockholm University. We have produced beams of atomic carbon anions and small carbon anion molecules (Cn-, n = 1, 2, 3, 4) in a sputter ion source. The ion beams were accelerated to 10 keV kinetic energy and stored in an electrostatic ion storage ring enclosed in a vacuum chamber at 13 K. For 10 keV C2- molecular anions we measure the residual-gas limited beam storage lifetime to be 448 s +/- 18 s with two independent detector systems. Using the measured storage lifetimes we estimate that the residual gas pressure is in the 10-14 mbar range. When high current ion beams are injected, the number of stored particles does not follow a single exponential decay law as would be expected for stored particles lost solely due to electron detachment in collision with the residual-gas. Instead, we observe a faster initial decay rate, which we ascribe to the effect of the space charge of the ion beam on the storage capacity.
  •  
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