| 1. |
- Keogan, Katharine, et al.
(författare)
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Global phenological insensitivity to shifting ocean temperatures among seabirds
- 2018
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Ingår i: Nature Climate Change. - : Springer Science and Business Media LLC. - 1758-678X .- 1758-6798. ; 8:4, s. 313-318
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Tidskriftsartikel (refereegranskat)abstract
- Reproductive timing in many taxa plays a key role in determining breeding productivity(1), and is often sensitive to climatic conditions(2). Current climate change may alter the timing of breeding at different rates across trophic levels, potentially resulting in temporal mismatch between the resource requirements of predators and their prey(3). This is of particular concern for higher-trophic-level organisms, whose longer generation times confer a lower rate of evolutionary rescue than primary producers or consumers(4). However, the disconnection between studies of ecological change in marine systems makes it difficult to detect general changes in the timing of reproduction(5). Here, we use a comprehensive meta-analysis of 209 phenological time series from 145 breeding populations to show that, on average, seabird populations worldwide have not adjusted their breeding seasons over time (-0.020 days yr(-1)) or in response to sea surface temperature (SST) (-0.272 days degrees C-1) between 1952 and 2015. However, marked between-year variation in timing observed in resident species and some Pelecaniformes and Suliformes (cormorants, gannets and boobies) may imply that timing, in some cases, is affected by unmeasured environmental conditions. This limited temperature-mediated plasticity of reproductive timing in seabirds potentially makes these top predators highly vulnerable to future mismatch with lower-trophic-level resources(2).
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| 2. |
- Berglund, Lisa, et al.
(författare)
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Glucose-Dependent Insulinotropic Polypeptide (GIP) Stimulates Osteopontin Expression in the Vasculature via Endothelin-1 and CREB.
- 2016
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 65:1, s. 239-254
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Tidskriftsartikel (refereegranskat)abstract
- Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone with extrapancreatic effects beyond glycemic control. Here we demonstrate unexpected effects of GIP signaling in the vasculature. GIP induces the expression of the pro-atherogenic cytokine osteopontin (OPN) in mouse arteries, via local release of endothelin-1 (ET-1) and activation of cAMP response element binding protein (CREB). Infusion of GIP increases plasma OPN levels in healthy individuals. Plasma ET-1 and OPN levels are positively correlated in patients with critical limb ischemia. Fasting GIP levels are higher in individuals with a history of cardiovascular disease (myocardial infarction, stroke) when compared to controls. GIP receptor (GIPR) and OPN mRNA levels are higher in carotid endarterectomies from patients with symptoms (stroke, transient ischemic attacks, amaurosis fugax) than in asymptomatic patients; and expression associates to parameters characteristic of unstable and inflammatory plaques (increased lipid accumulation, macrophage infiltration and reduced smooth muscle cell content). While GIPR expression is predominantly endothelial in healthy arteries from human, mouse, rat and pig; remarkable up-regulation is observed in endothelial and smooth muscle cells upon culture conditions yielding a "vascular disease-like" phenotype. Moreover, a common variant rs10423928 in the GIPR gene associated with increased risk of stroke in type 2 diabetes patients.
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| 3. |
- Enhörning, Sofia, et al.
(författare)
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Plasma copeptin and the risk of diabetes mellitus.
- 2010
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Ingår i: Circulation. - 1524-4539. ; 121:19, s. 51-2102
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Animal studies suggest that the arginine vasopressin system may play a role in glucose metabolism, but data from humans are limited. METHODS AND RESULTS: We analyzed plasma copeptin (copeptin), a stable C-terminal fragment of the arginine vasopressin prohormone. Using baseline and longitudinal data from a Swedish population-based sample (n=4742; mean age, 58 years; 60% women) and multivariable logistic regression, we examined the association of increasing quartiles of copeptin (lowest quartile as reference) with prevalent diabetes mellitus at baseline, insulin resistance (top quartile of fasting plasma insulin among nondiabetic subjects), and incident diabetes mellitus on long-term follow-up. New-onset diabetes mellitus was ascertained through 3 national and regional registers. All models were adjusted for clinical and anthropometric risk factors, cystatin C, and C-reactive protein. In cross-sectional analyses, increasing copeptin was associated with prevalent diabetes mellitus (P=0.04) and insulin resistance (P<0.001). During 12.6 years of follow-up, 174 subjects (4%) developed new-onset diabetes mellitus. The odds of developing diabetes mellitus increased across increasing quartiles of copeptin, even after additional adjustment for baseline fasting glucose and insulin (adjusted odds ratios, 1.0, 1.37, 1.79, and 2.09; P for trend=0.004). The association with incident diabetes mellitus remained significant in analyses restricted to subjects with fasting whole blood glucose <5.4 mmol/L at baseline (adjusted odds ratios, 1.0, 1.80, 1.92, and 3.48; P=0.001). CONCLUSIONS: Elevated copeptin predicts increased risk for diabetes mellitus independently of established clinical risk factors, including fasting glucose and insulin. These findings could have implications for risk assessment, novel antidiabetic treatments, and metabolic side effects from arginine vasopressin system modulation.
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| 4. |
- Fröbom, Robin, et al.
(författare)
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Phase I trial evaluating safety and efficacy of intratumorally administered inflammatory allogeneic dendritic cells (ilixadencel) in advanced gastrointestinal stromal tumors
- 2020
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Ingår i: Cancer Immunology and Immunotherapy. - : Springer Science and Business Media LLC. - 0340-7004 .- 1432-0851. ; 69:11, s. 2393-2401
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe majority of patients with advanced gastrointestinal stromal tumor (GIST) develop resistance to imatinib, and subsequent treatments have limited efficacy. Ilixadencel (allogeneic inflammatory dendritic cells) is a cell-based immune primer injected intratumorally that previously has been clinically investigated in metastatic renal cell carcinoma and hepatocellular carcinoma.MethodsThe trial was a single arm phase I trial assessing safety and efficacy of ilixadencel in subjects with progressing advanced/metastatic GIST despite ongoing treatment with second or later lines of tyrosine kinase inhibitors (TKI). Three patients were progressing while on sunitinib (second line), one on regorafenib (third line), and two on pazopanib (fourth line). TKI treatment was maintained throughout, while two intratumoral injections of ilixadencel (10 × 106 viable and HLA-DR expressing cells per dose) were administered.ResultsNo severe adverse events were found to be related to ilixadencel administration. Four patients showed continued tumor progression at 3 months per RECIST 1.1 and Choi criteria. One patient (on third line regorafenib) had stable disease for 9 months and another patient (on second line sunitinib) had stable disease at end of study (12 months) as per RECIST 1.1. These two patients developed a partial response as per Choi criteria with a duration of 3 and 6 months, respectively. The median progression-free survival (PFS) was 4.0 months.ConclusionIlixadencel treatment presented an acceptable safety profile among advanced GIST patients who developed resistance to TKI. Encouraging radiological tumor responses were detected in 33% of treated patients, supporting further investigation.
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| 5. |
- Jones, Geraint H., et al.
(författare)
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The Comet Interceptor Mission
- 2024
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Ingår i: Space Science Reviews. - : Springer Nature. - 0038-6308 .- 1572-9672. ; 220:1
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Tidskriftsartikel (refereegranskat)abstract
- Here we describe the novel, multi-point Comet Interceptor mission. It is dedicated to the exploration of a little-processed long-period comet, possibly entering the inner Solar System for the first time, or to encounter an interstellar object originating at another star. The objectives of the mission are to address the following questions: What are the surface composition, shape, morphology, and structure of the target object? What is the composition of the gas and dust in the coma, its connection to the nucleus, and the nature of its interaction with the solar wind? The mission was proposed to the European Space Agency in 2018, and formally adopted by the agency in June 2022, for launch in 2029 together with the Ariel mission. Comet Interceptor will take advantage of the opportunity presented by ESA’s F-Class call for fast, flexible, low-cost missions to which it was proposed. The call required a launch to a halo orbit around the Sun-Earth L2 point. The mission can take advantage of this placement to wait for the discovery of a suitable comet reachable with its minimum Δ V capability of 600 ms − 1 . Comet Interceptor will be unique in encountering and studying, at a nominal closest approach distance of 1000 km, a comet that represents a near-pristine sample of material from the formation of the Solar System. It will also add a capability that no previous cometary mission has had, which is to deploy two sub-probes – B1, provided by the Japanese space agency, JAXA, and B2 – that will follow different trajectories through the coma. While the main probe passes at a nominal 1000 km distance, probes B1 and B2 will follow different chords through the coma at distances of 850 km and 400 km, respectively. The result will be unique, simultaneous, spatially resolved information of the 3-dimensional properties of the target comet and its interaction with the space environment. We present the mission’s science background leading to these objectives, as well as an overview of the scientific instruments, mission design, and schedule.
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| 6. |
- Jujić, Amra, et al.
(författare)
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Glucose-dependent insulinotropic peptide and risk of cardiovascular events and mortality : a prospective study
- 2020
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Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 63:5, s. 1043-1054
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: Evidence that glucose-dependent insulinotropic peptide (GIP) and/or the GIP receptor (GIPR) are involved in cardiovascular biology is emerging. We hypothesised that GIP has untoward effects on cardiovascular biology, in contrast to glucagon-like peptide 1 (GLP-1), and therefore investigated the effects of GIP and GLP-1 concentrations on cardiovascular disease (CVD) and mortality risk.Methods: GIP concentrations were successfully measured during OGTTs in two independent populations (Malmo Diet Cancer-Cardiovascular Cohort [MDC-CC] and Prevalence, Prediction and Prevention of Diabetes in Botnia [PPP-Botnia]) in a total of 8044 subjects. GLP-1 (n = 3625) was measured in MDC-CC. The incidence of CVD and mortality was assessed via national/regional registers or questionnaires. Further, a two-sample Mendelian randomisation (2SMR) analysis between the GIP pathway and outcomes (coronary artery disease [CAD] and myocardial infarction) was carried out using a GIP-associated genetic variant, rs1800437, as instrumental variable. An additional reverse 2SMR was performed with CAD as exposure variable and GIP as outcome variable, with the instrumental variables constructed from 114 known genetic risk variants for CAD.Results: In meta-analyses, higher fasting levels of GIP were associated with risk of higher total mortality (HR[95% CI] = 1.22 [1.11, 1.35]; p = 4.5 x 10(-5)) and death from CVD (HR[95% CI] 1.30 [1.11, 1.52]; p = 0.001). In accordance, 2SMR analysis revealed that increasing GIP concentrations were associated with CAD and myocardial infarction, and an additional reverse 2SMR revealed no significant effect of CAD on GIP levels, thus confirming a possible effect solely of GIP on CAD.Conclusions/interpretation: In two prospective, community-based studies, elevated levels of GIP were associated with greater risk of all-cause and cardiovascular mortality within 5-9 years of follow-up, whereas GLP-1 levels were not associated with excess risk. Further studies are warranted to determine the cardiovascular effects of GIP per se.
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| 7. |
- Lyssenko, Valeriya, et al.
(författare)
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Clinical risk factors, DNA variants, and the development of type 2 diabetes.
- 2008
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 359:21, s. 2220-2232
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Type 2 diabetes mellitus is thought to develop from an interaction between environmental and genetic factors. We examined whether clinical or genetic factors or both could predict progression to diabetes in two prospective cohorts. METHODS: We genotyped 16 single-nucleotide polymorphisms (SNPs) and examined clinical factors in 16,061 Swedish and 2770 Finnish subjects. Type 2 diabetes developed in 2201 (11.7%) of these subjects during a median follow-up period of 23.5 years. We also studied the effect of genetic variants on changes in insulin secretion and action over time. RESULTS: Strong predictors of diabetes were a family history of the disease, an increased body-mass index, elevated liver-enzyme levels, current smoking status, and reduced measures of insulin secretion and action. Variants in 11 genes (TCF7L2, PPARG, FTO, KCNJ11, NOTCH2, WFS1, CDKAL1, IGF2BP2, SLC30A8, JAZF1, and HHEX) were significantly associated with the risk of type 2 diabetes independently of clinical risk factors; variants in 8 of these genes were associated with impaired beta-cell function. The addition of specific genetic information to clinical factors slightly improved the prediction of future diabetes, with a slight increase in the area under the receiver-operating-characteristic curve from 0.74 to 0.75; however, the magnitude of the increase was significant (P=1.0x10(-4)). The discriminative power of genetic risk factors improved with an increasing duration of follow-up, whereas that of clinical risk factors decreased. CONCLUSIONS: As compared with clinical risk factors alone, common genetic variants associated with the risk of diabetes had a small effect on the ability to predict the future development of type 2 diabetes. The value of genetic factors increased with an increasing duration of follow-up.
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| 8. |
- Lyssenko, Valeriya, et al.
(författare)
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Mechanisms by which common variants in the TCF7L2 gene increase risk of type 2 diabetes.
- 2007
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Ingår i: Journal of Clinical Investigation. - 0021-9738. ; 117:8, s. 2155-2163
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants in the gene encoding for transcription factor-7-like 2 (TCF7L2) have been associated with type 2 diabetes (T2D) and impaired beta cell function, but the mechanisms have remained unknown. We therefore studied prospectively the ability of common variants in TCF7L2 to predict future T2D and explored the mechanisms by which they would do this. Scandinavian subjects followed for up to 22 years were genotyped for 3 SNPs (rs7903146, rs12255372, and rs10885406) in TCF7L2, and a subset of them underwent extensive metabolic studies. Expression of TCF7L2 was related to genotype and metabolic parameters in human islets. The CT/TT genotypes of SNP rs7903146 strongly predicted future T2D in 2 independent cohorts (Swedish and Finnish). The risk T allele was associated with impaired insulin secretion, incretin effects, and enhanced rate of hepatic glucose production. TCF7L2 expression in human islets was increased 5-fold in T2D, particularly in carriers of the TT genotype. Overexpression of TCF7L2 in human islets reduced glucose-stimulated insulin secretion. In conclusion, the increased risk of T2D conferred by variants in TCF7L2 involves the enteroinsular axis, enhanced expression of the gene in islets, and impaired insulin secretion.
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| 9. |
- Lyssenko, Valeriya, et al.
(författare)
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Pleiotropic Effects of GIP on Islet Function Involve Osteopontin
- 2011
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 60:9, s. 2424-2433
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE-The incretin hormone GIP (glucose-dependent insulinotropic polypeptide) promotes pancreatic beta-cell function by potentiating insulin secretion and beta-cell proliferation. Recently, a combined analysis of several genome-wide association studies (Meta-analysis of Glucose and Insulin-Related Traits Consortium [MAGIC]) showed association to postprandial insulin at the GIP receptor (GIPR) locus. Here we explored mechanisms that could explain the protective effects of GIP on islet function. RESEARCH DESIGN AND METHODS-Associations of GIPR rs10423928 with metabolic and anthropometric phenotypes in both nondiabetic (N = 53,730) and type 2 diabetic individuals (N = 2,731) were explored by combining data from 11 studies.Insulin secretion was measured both in vivo in nondiabetic subjects and in vitro in islets from cadaver donors. Insulin secretion was also measured in response to exogenous GIP. The in vitro measurements included protein and gene expression as well as measurements of beta-cell viability and proliferation. RESULTS-The A allele of GIPR rs10423928 was associated with impaired glucose- and GIP-stimulated insulin secretion and a decrease in BMI, lean body mass, and waist circumference. The decrease in BMI almost completely neutralized the effect of impaired insulin secretion on risk of type 2 diabetes. Expression of GIPR mRNA was decreased in human islets from carriers of the A allele or patients with type 2 diabetes. GIP stimulated osteopontin (OPN) mRNA and protein expression. OPN expression was lower in carriers of the A allele. Both GIP and OPN prevented cytokine-induced reduction in cell viability (apoptosis). In addition, OPN stimulated cell proliferation in insulin-secreting cells. CONCLUSIONS-These findings support beta-cell proliferative and antiapoptotic roles for GIP in addition to its action as an incretin hormone. Identification of a link between GIP and OPN may shed new light on the role of GIP in preservation of functional beta-cell mass in humans. Diabetes 60:2424-2433, 2011
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| 10. |
- Lövenheim, Boel, et al.
(författare)
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Health risk assessment of reduced air pollution exposure when changing commuting by car to bike
- 2016
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Konferensbidrag (refereegranskat)abstract
- In this study we have assessed the reduction in traffic emissions and population exposure assuming all potential car commuters would switch to biking if they live within 30 minute travel by bike. The scenario would result in more than 100 000 new bikers and due to the reduced traffic emissions 42 premature deaths would be avoided per year. This is almost twice as large effect as the congestion tax in Stockholm. Introduction Regular physical activity has important and wide-ranging health benefits including reduced risk of chronic disease, and physical inactivity is mentioned as perhaps the most important public health problem of the 21st century. At the same time, the direct effects of traffic emissions is a major health problem. Transferring commuting by car to bike will increase physical activity and reduce emissions and reduce population exposure to traffic pollution. The exposure of commuters will also change; new bikers may get higher exposure whilst old bikers and car drivers may get lower exposures, depending on commuting route and distance. Methodology In this study we have calculated the potential number of car-to-bike switching commuters depending on distance, travel time, age of commuters, etc. We have made calculations for a 30-minute biking scenario, i.e. transferring all car commuters to bike if their travel time by bike is less than or equal to 30 minutes. The commuting distance depends on age and sex. For the travel and traffic modelling the LuTrans model was used. It includes all different modes of travel; walking, bicycling, public transport systems and car traffic. The model was developed based on travel survey data and is regularly calibrated using traffic counts. Emissions from road traffic were calculated based on HBEFA 3.2. A Gaussian dispersion model was used estimate exposures over the county of Stockholm. Results The 30 min scenario resulted in 106 881 more bikers, an increase of 2.6 times compared to base scenario. Of all bikers 50% were men and the mean age of all bikers was 42. The traffic emissions of NOx was reduced by up to 7%. Up to 20% reduction in traffic contribution to NOx concentrations was calculated as shown in Figure 1. The mean reduction in concentration for the whole area is 6% and the largest occur were most people live.The population weighted mean NOx concentration for 1.6 million people in Greater Stockholm is estimated to be reduced by 0.41 μg m-3. Assuming that the premature mortality is reduced by 8% per 10 μg m-3 (Nafstad et al., 2004), this corresponds to 42 avoided premature deaths every year or 514 gained life years gained. This is even somewhat more beneficial than the effects of the congestion charge in Stockholm (Johansson et al., 2009), which was estimated to save 27 premature deaths per year. The gain in reduced mortality is almost as large as the gain in health of the increased physical activity. Conclusions Transferring car commuters to bike is not only beneficial for the physical activity, but will also lead to reduced traffic emissions and reduced population exposure. Our estimates show that it may be even more beneficial for mortality due to air pollution exposure than the congestion charge in Stockholm. Acknowledgement This project was funded by the Swedish Research Council for Health, Working life and Welfare. References Johansson, C., Burman, L., Forsberg, B. 2009. The effects of congestions tax on air quality and health. Atmos. Environ. 43, 4843-4854.Nafstad, P., Lund Håheim, L., Wisloeff, T., Gram, G., Oftedal, B., Holme, I., Hjermann, I. and Leren, P. 2004. Urban Air Pollution and Mortality in a Cohort of Norwegian Men. Environ. Health Perspect. 112, 610-615.
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| 11. |
- Newton-Cheh, Christopher, et al.
(författare)
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Genome-wide association study identifies eight loci associated with blood pressure
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:6, s. 666-676
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N <= 71,225 European ancestry, N <= 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 x 10(-24)), CYP1A2 (P = 1 x 10(-23)), FGF5 (P = 1 x 10(-21)), SH2B3 (P = 3 x 10(-18)), MTHFR (P = 2 x 10(-13)), c10orf107 (P = 1 x 10(-9)), ZNF652 (P = 5 x 10(-9)) and PLCD3 (P = 1 x 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.
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| 12. |
- Saxena, Richa, et al.
(författare)
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Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels
- 2007
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 316:5829, s. 1331-1336
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Tidskriftsartikel (refereegranskat)abstract
- New strategies for prevention and treatment of type 2 diabetes (T2D) require improved insight into disease etiology. We analyzed 386,731 common single-nucleotide polymorphisms (SNPs) in 1464 patients with T2D and 1467 matched controls, each characterized for measures of glucose metabolism, lipids, obesity, and blood pressure. With collaborators (FUSION and WTCCC/UKT2D), we identified and confirmed three loci associated with T2D - in a noncoding region near CDKN2A and CDKN2B, in an intron of IGF2BP2, and an intron of CDKAL1 - and replicated associations near HHEX and in SLC30A8 found by a recent whole-genome association study. We identified and confirmed association of a SNP in an intron of glucokinase regulatory protein (GCKR) with serum triglycerides. The discovery of associated variants in unsuspected genes and outside coding regions illustrates the ability of genome-wide association studies to provide potentially important clues to the pathogenesis of common diseases.
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| 13. |
- van Tour, Peter, 1966-
(författare)
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Counterpoint and Partimento : Methods of Teaching Composition in Late Eighteenth-Century Naples
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- During the second half of the eighteenth century, the city of Naples had three music conservatories: the Conservatorio di Santa Maria di Onofrio, the Conservatorio di Santa Maria di Loreto, and the Conservatorio di Santa Maria della Pietà de’ Turchini. Through disciplines such as solfeggio, partimento, and counterpoint, the students at these institutions received highly professional training in singing, instrumental playing, and composition.This study reveals new evidence that partimenti were used not only as exercises in keyboard playing, but also as exercises in written counterpoint. As counterpoint exercises, partimenti were used either as bass lines over which students wrote one or several contrapuntal parts, or as notational devices that facilitated the sketching of fugues.Musicologists have previously encountered considerable difficulties in identifying and describing differences between the schools of Leonardo Leo and Francesco Durante, represented by the terms Leisti and Durantisti. This study shows that these schools are primarily defined through different methods of teaching counterpoint. Contemporary counterpoint notebooks show that the maestri at Sant’Onofrio and Santa Maria di Loreto followed Durante’s teaching methods, while the maestri at La Pietà followed Leo’s teaching methods. The school of Durante emphasized the writing of melodic lines over a hexachordal scale or a partimento bass, using different methods, such as the moti del basso and prescribed conditions. The school of Leo favored the use of invertible counterpoint, emphasizing skills in sketching and writing choral fugues from subjects and countersubjects.For the first time, the partimento and solfeggio repertoire used at the Neapolitan conservatories has been systematically investigated through the creation of two research tools, the databases UUPart: The Uppsala Partimento Database and UUSolf: The Uppsala Solfeggio Database, published online on two companion websites.
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| 14. |
- Wilhelmsson, Peter, et al.
(författare)
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A prospective study on the incidence of Borrelia burgdorferi sensu lato infection after a tick bite in Sweden and On the Åland Islands, Finland (2008-2009)
- 2016
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Ingår i: Ticks and Tick-borne Diseases. - : Elsevier. - 1877-959X .- 1877-9603. ; 7:1, s. 71-79
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Tidskriftsartikel (refereegranskat)abstract
- Lyme borreliosis (LB) is a common and increasing tick-borne disease in Europe. The risk of acquiring a Borrelia infection after a tick bite is not fully known. Therefore, we investigated the incidence of Borrelia infection after a bite by a Borrelia-infected tick and if the Borrelia load and/or the duration of tick-feeding influenced the risk of infection. During 2008-2009, ticks and blood samples were collected from 1546 tick-bitten persons from Sweden and the Åland Islands, Finland. Follow-up blood samples were taken 3 months after the tick bite. The duration of tick feeding was microscopically estimated and Borrelia was detected and quantified in ticks by real-time PCR. Anti-Borrelia antibodies were detected in sera using ELISA tests and immunoblot. Five percent (78/1546) of the study participants developed Borrelia infection (LB diagnosis and/or seroconversion) after a tick bite (45% bitten by Borrelia-infected ticks and 55% bitten by uninfected ticks). Of these, 33 developed LB (whereof 9 also seroconverted) while 45 participants seroconverted only. Experience of non-specific symptoms was more frequently reported by Borrelia-infected participants compared to uninfected participants. All who seroconverted removed "their" ticks significantly later than those who did not. The Borrelia load in the ticks did not explain the risk of seroconversion. Regional and sex differences in the Borrelia seroprevalence were found. The risk of developing a Borrelia infection after a bite by a Borrelia-infected tick is small but increases with the duration of tick feeding.
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| 15. |
- Wilhelmsson, Peter, et al.
(författare)
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A prospective study on the incidence of Borrelia infection after a tick bite in Sweden and on the Åland Islands, Finland (2008-2009)
- 2016
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Ingår i: Ticks and Tick-borne Diseases. - : Elsevier. - 1877-959X .- 1877-9603. ; 7:1, s. 71-79
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Tidskriftsartikel (refereegranskat)abstract
- Lyme borreliosis (LB) is a common and increasing tick-borne disease in Europe. The risk of acquiring a Borrelia infection after a tick bite is not fully known. Therefore, we investigated the incidence of Borrelia infection after a tick bite and if the Borrelia load and/or the duration of tick-feeding influenced the risk of infection. During 2008-2009, ticks and blood samples were collected from 1546 tick-bitten persons from Sweden and the Åland Islands, Finland. Follow-up blood samples were taken three months after the tick bite. The duration of tick feeding was microscopically estimated and Borrelia was detected and quantified in ticks by real-time PCR. Anti-Borrelia antibodies were detected in sera using ELISA assays and immunoblot.Even though 28 % of the participants were bitten by a Borrelia-positive tick, only 7.5% (32/428) of them developed a Borrelia infection, half of them LB. All who seroconverted removed “their” ticks significantly later than those who did not. The Borrelia load in the ticks did not explain the risk of seroconversion. Regional as well as gender differences in the Borrelia seroprevalence were found. The risk of developing a Borrelia infection after a bite by a Borrelia-infected tick is small but increases with the duration of tick feeding.
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| 16. |
- Aasa, Björn, et al.
(författare)
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A characterisation of pain, disability, kinesiophobia and physical capacity in patients with predominantly peripherally mediated mechanical low back pain
- 2011
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Ingår i: Physiotherapy. - 0031-9406 .- 1873-1465. ; 97:Suppl. 1, s. eS18-
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The specific objectives were to: 1) describe the level of pain intensity, disability, activity limitation, kinesiophobia and physical capacity in patients with predominantly peripherally mediated mechanical back pain, and 2) investigate whether differences between these patients in physical and psychosocial factors can be distinguished when the patients are further sub-grouped.Relevance: To improve assessment among patients with chronic low back pain (CLBP) it is important to investigate the prevalence of physical and psychosocial features in homogenous sub-groups.Participants: Seventy-one patients with CLBP, 20-60 years old, with peripherally mediated mechanical pain at the the moment for the study, were included and each patient was sub-classified into one of five sub-groups based on their pain behaviour and functional movement pattern (flexion n=20, flexion/lateral shift, n=11, active extension n=23 , passive extension n=8, and multidirectional pattern n=9).Methods: Data on pain intensity (Visual Analogue Scale), disability (the Roland and Morris Questionnaire), activity limitation (the Patient Specific Functional Scale), kinesiophobia (the Tampa Scale of Kinesiophobia) and physical capacity (lifting capacity and trunk extensor endurance) was collected.Analysis: Mean and standard deviation for parametric and median and interquartile range for non-parametric data were used for descriptive statistics. One-way ANOVA for normally distributed data and Kruskal-Wallis for non-normally distributed data were used for analyses of differences between the sub-groups. The subjects were also divided into two age-groups (20-40 and 41-60 years) and measures of physical capacity were compared to women and men at the ages of 34 and 50, respectively, in the general Swedish population using one sample T-test.Results: The patients reported low to moderate pain intensity (3.1/10±2.4), disability (RMDQ (7.27/24 ±4.2) and kinesiophobia (33.4/68 ±7) and these levels were lower than reported levels in other studies including more heterogenous groups of patients with CLBP. The patiens reported activity limitations (PSFS 13/30±23). Lifting capacity and trunk extensor endurance were significantly lower than in the general population in the youngest age-group. No significant differences in pain intensity, disability, kinesiophobia or physical capacity were found between the sub-groups.Conclusions: This research highlights that patients with predominantly peripherally mediated mechanical back pain may differ from other sub-groups of patients with CLBP (e.g., patients with central sensitization as dominating pain mechanism) regarding physical and psychosocial factors. The individual variation in pain intensity, disability, kinesiophbia and physical capacity among the patients indicates the importance to assess these factors in every patient. Due to the fact that there were few patients in the sub-groups, further research is necessary to explore whether there are differences, that we were not able to disingjish, between patients with different movement patterns.
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| 17. |
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| 18. |
- Aasa, Björn, et al.
(författare)
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Individualized low-load motor control exercises and education versus a high-load lifting exercise and education to improve activity, pain intensity, and physical performance in patients with low back pain : a randomized controlled trial
- 2015
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Ingår i: Journal of Orthopaedic and Sports Physical Therapy. - : Journal of Orthopaedic & Sports Physical Therapy (JOSPT). - 0190-6011 .- 1938-1344. ; 45:2, s. 77-85
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Tidskriftsartikel (refereegranskat)abstract
- Study Design Randomized controlled trial. Background Low back pain is a common disorder. Patients with low back pain frequently have aberrant and pain-provocative movement patterns that often are addressed with motor control exercises. Objective To compare the effects of low-load motor control (LMC) exercise and those of a high-load lifting (HLL) exercise. Methods Seventy participants with recurrent low back pain, who were diagnosed with nociceptive mechanical pain as their dominating pain pattern, were randomized to either LMC or HLL exercise treatments. Participants were offered 12 treatment sessions over an 8-week period. All participants were also provided with education regarding pain mechanisms. Methods Participants were assessed prior to and following treatment. The primary outcome measures were activity (the Patient-Specific Functional Scale) and average pain intensity over the last 7 days (visual analog scale). The secondary outcome measure was a physical performance test battery that included 1 strength, 3 endurance, and 7 movement control tests for the lumbopelvic region. Results Both interventions resulted in significant within-group improvements in pain intensity, strength, and endurance. The LMC group showed significantly greater improvement on the Patient-Specific Functional Scale (4.2 points) compared with the HLL group (2.5 points) (P<.001). There were no significant between-group differences in pain intensity (P = .505), strength, and 1 of the 3 endurance tests. However, the LMC group showed an increase (from 2.9 to 5.9) on the movement control test subscale, whereas the HLL group showed no change (from 3.9 to 3.1) (P<.001). Conclusion An LMC intervention may result in superior outcomes in activity, movement control, and muscle endurance compared to an HLL intervention, but not in pain intensity, strength, or endurance.
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| 19. |
- Abahazi, Emese, et al.
(författare)
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Covalently immobilized Trp60Cys mutant of omega‰-transaminase from Chromobacterium violaceum for kinetic resolution of racemic amines in batch and continuous-flow modes
- 2018
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Ingår i: Biochemical engineering journal. - : Elsevier. - 1369-703X .- 1873-295X. ; 132, s. 270-278
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Tidskriftsartikel (refereegranskat)abstract
- Covalent immobilization of an engineered omega-transaminase mutant Trp60Cys from Chromobacterium violaceum (CvTAW60C) was performed on bisepoxide-activated aminoalkyl resins. Activity of the various CvTAW60C preparations was evaluated in kinetic resolution of four racemic amines (rac-1a–d). The most active EA-G-CvTAW60C preparation (CvTAW60C attached to polymeric resin with ethylamine function activated with glycerol diglycidyl ether—EA-G) could perform the kinetic resolution of racemic 4-phenylbutan-2-amine (rac-1a) over 49% conversion up to 19 consecutive reaction cycles or in media containing up to 50% v/v DMSO as cosolvent in batch mode reactions. The immobilization process of CvTAW60C onto the EA-G resin filled in stainless steel bioreactors was also tested in flow-through mode. Kinetic resolution of three racemic amines containing aromatic moieties (rac-1a-c) was performed in continuous-flow mode resulting in easy-to-separate mixture of the corresponding ketone (2a–c) and the non-converted (R)-amine in high enantiopurity (ee(R)-1a-c ≥ 96%).
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| 20. |
- Abdulla, Maysaa, et al.
(författare)
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PD-L1 and IDO1 are potential targets for treatment in patients with primary diffuse large B-cell lymphoma of the CNS
- 2021
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 60:4, s. 531-538
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundProgrammed cell death 1 (PD-1) and its ligands PD-L1 and PD-L2, as well as Indoleamine 2,3-deoxygenase (IDO1) can be expressed both by tumor and microenvironmental cells and are crucial for tumor immune escape. We aimed to evaluate the role of PD-1, its ligands and IDO1 in a cohort of patients with primary diffuse large B-cell lymphoma of the CNS (PCNSL).Material and methodsTissue microarrays (TMAs) were constructed in 45 PCNSL cases. RNA extraction from whole tissue sections and RNA sequencing were successfully performed in 33 cases. Immunohistochemical stainings for PD-1, PD-L1/paired box protein 5 (PAX-5), PD-L2/PAX-5 and IDO1, and Epstein-Barr virus encoding RNA (EBER) in situ hybridization were analyzed.ResultsHigh proportions of PD-L1 and PD-L2 positive tumor cells were observed in 11% and 9% of cases, respectively. High proportions of PD-L1 and PD-L2 positive leukocytes were observed in 55% and 51% of cases, respectively. RNA sequencing revealed that gene expression of IDO1 was high in patients with high proportion of PD-L1 positive leukocytes (p = .01). Protein expression of IDO1 in leukocytes was detected in 14/45 cases, in 79% of these cases a high proportion of PD-L1 positive leukocytes was observed. Gene expression of IDO1 was high in EBER-positive cases (p = .0009) and protein expression of IDO1 was detected in five of six EBER-positive cases.ConclusionOur study shows a significant association between gene and protein expression of IDO1 and protein expression of PD-L1 in the tumor microenvironment of PCNSL, possibly of importance for prediction of response to immunotherapies.
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| 21. |
- Aeddula, Omsri, 1993-, et al.
(författare)
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A Solution with Bluetooth Low Energy Technology to Support Oral Healthcare Decisions for improving Oral Hygiene
- 2021
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Ingår i: ACM International Conference Proceeding Series. - New York, NY, USA : Association for Computing Machinery (ACM). - 9781450389846 ; , s. 134-139
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Konferensbidrag (refereegranskat)abstract
- The advent of powered toothbrushes and associated mobile health applications provides an opportunity to collect and monitor the data, however collecting reliable and standardized data from large populations has been associated with efforts from the participants and researchers. Finding a way to collect data autonomously and without the need for cooperation imparts the potential to build large knowledge banks. A solution with Bluetooth low energy technology is designed to pair a powered toothbrush with a single-core processor to collect raw data in a real-time scenario, eliminating the manual transfer of powered toothbrush data with mobile health applications. Associating powered toothbrush with a single-core processor is believed to provide reliable and comprehensible data of toothbrush use and propensities can be a guide to improve individual exhortation and general plans on oral hygiene quantifies that can prompt improved oral wellbeing. The method makes a case for an expanded chance to plan assistant capacities to protect or improve factors that influence oral wellbeing in individuals with mild cognitive impairment. The proposed framework assists with determining various parameters, which makes it adaptable and conceivable to execute in various oral care contexts
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| 22. |
- Aeddula, Omsri, 1993-, et al.
(författare)
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AI-driven Ossification Assessment in Knee MRI : A Product-Service System Development for Informed Clinical Decision-Making
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Traditionally, assessing the degree of ossification in the epiphyseal plate for growth plate development relies on manual evaluation, which can be inefficient due to the complexities of the distal femoral epiphysis anatomy. Existing methods lack efficient detection techniques.Method: This study proposes an AI-based decision support system, designed within a product-service system (PSS) framework, to automate ossification assessment and detection of the distal femoral epiphysis in knee magnetic resonance imaging (MRI) data. The system leverages advanced machine learning techniques, specifically two Convolutional Neural Networks (CNNs), combined with computer vision techniques. This intelligent system analyzes MRI slices to predict the optimal slice for analysis and identify variations in the degree of ossification within individual datasets.Results: The proposed method's effectiveness is demonstrated using a set of T2-weighted gradient echo grayscale knee MRI data. The system successfully detects the complex anatomy of the distal femoral epiphysis, revealing variations in the degree of ossification ranging from completely closed/open to fully open/closed regions.Conclusions: This study presents a robust and efficient AI-based method, integrated within a PSS framework, for measuring the degree of ossification in the distal femoral epiphysis. This approach automates ossification assessment, providing valuable insights for clinical decision-making by clinicians and forensic practitioners. The PSS framework ensures seamless integration of the AI technology into existing workflows.
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| 23. |
- Aeddula, Omsri, 1993-
(författare)
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Data-Driven Decision Support Systems for Product Development - A Data Exploration Study Using Machine Learning
- 2021
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Modern product development is a complex chain of events and decisions. The ongoing digital transformation of society, increasing demands in innovative solutions puts pressure on organizations to maintain, or increase competitiveness. As a consequence, a major challenge in the product development is the search for information, analysis, and the build of knowledge. This is even more challenging when the design element comprises complex structural hierarchy and limited data generation capabilities. This challenge is even more pronounced in the conceptual stage of product development where information is scarce, vague, and potentially conflicting. The ability to conduct exploration of high-level useful information using a machine learning approach in the conceptual design stage would hence enhance be of importance to support the design decision-makers, where the decisions made at this stage impact the success of overall product development process.The thesis aims to investigate the conceptual stage of product development, proposing methods and tools in order to support the decision-making process by the building of data-driven decision support systems. The study highlights how the data can be utilized and visualized to extract useful information in design exploration studies at the conceptual stage of product development. The ability to build data-driven decision support systems in the early phases facilitates more informed decisions.The thesis presents initial descriptive study findings from the empirical studies, showing the capabilities of the machine learning approaches in extracting useful information, and building data-driven decision support systems. The thesis initially describes how the linear regression model and artificial neural networks extract useful information in design exploration, providing support for the decision-makers to understand the consequences of the design choices through cause-and-effect relationships on a detailed level. Furthermore, the presented approach also provides input to a novel visualization construct intended to enhance comprehensibility within cross-functional design teams. The thesis further studies how the data can be augmented and analyzed to extract the necessary information from an existing design element to support the decision-making process in an oral healthcare context.
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| 24. |
- Aeddula, Omsri, 1993-
(författare)
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Navigating Data Challenges: AI-Driven Decision Support for Product-Service System Development
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Solution providers are transitioning from product-centric models to service-oriented solutions. This shift has led to the rise of Product-Service Systems (PSS), which offer a holistic approach by integrating physical products with associated services. However, the inherent complexity and collaborative nature of PSS development present a significant challenge: information gathering, analysis, and knowledge building. This is further amplified in the early stages of PSS development due to data challenges such as uncertainty, ambiguity, and complexity. This complicates informed decision-making, potentially leading to the risk of sub-optimal outcomes and impacting the success of final offerings.This research proposes an AI-powered data analysis approach to address these data challenges and augment the decision-making process of PSS development. The focus is on supporting early-stage decision-making, as decisions made at this stage greatly impact the success of final solutions. The research investigates how data can be utilized and visualized to extract actionable insights, ultimately facilitating informed decision-making.The presented research demonstrates that AI-powered data analysis effectively supports informed decision-making in early-stage PSS development. By extracting actionable insights from complex data, handling data limitations, and enabling informed strategic decisions, knowledge sharing, and collaboration are facilitated among stakeholders. Furthermore, integrating AI with visualization tools fosters knowledge building and a deeper understanding of system behavior, ultimately leading to more successful PSS solutions. The efficacy of AI-powered data analysis for handling diverse data types across application domains is demonstrated, potentially leading to benefits such as a deeper understanding of system behavior and proactive solution strategies. These advancements contribute to developing decision support systems specifically for PSS development.Overall, this research demonstrates the efficacy of AI-powered data analysis in overcoming data challenges and empowering decision-makers in early-stage PSS development. This translates to more informed choices, leading to the creation of successful and efficient PSS solutions.
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| 25. |
- Ahmer, Muhammad
(författare)
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Intelligent fault diagnosis and predictive maintenance for a bearing ring grinder
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Predicting the failure of any structure is a difficult task in a mechanical system. However complicated and difficult the prediction might be, the first step is to know the actual condition of the system. Given the complexity of any machine tool, where a number of subsystems of electro-mechanical structures interact to perform the machining operation, failure diagnostics become more challenging due to the high demand for performance and reliability. In a production environment, this results in maintenance costs that the management always strives to reduce. Condition-based machine maintenance (CBM) is considered to be the maintenance strategy that can lead to failure prediction and reducing the maintenance cost by knowing the actual condition of the asset and planning the maintenance activities in advance.Grinding machines and grinding processes have come a long way since the inception of the centuries old grinding technique. However, we still have a number of challenges to overcome before a completely monitored and controlled machine and process can be claimed. One such challenge is to achieve a machine level CBM and predictive maintenance (PdM) setup which is addressed in this thesis. A CBM implementation framework has been proposed which combines the information sampled from sensors installed for the purpose of the process as well as condition monitoring. Accessing the machine's controller information allows the data to be processed with respect to different machine states and process stages. The successful implementation is achieved through a real-time and synchronized data acquisition setup that allows data from multiple sources to be acquired, stored, and consolidated. The dataset thus generated is used in a significant part of this project and is also published in Swedish National Data Service (SND).The thesis also presents the failure diagnostic model based on two step classification approach using benchmarked random forest models. The binary classifier predicts if there is a fault present in the machine based on crucial sensors data from the Idle segment of the grinding cycle. Multi-class random forest classifier diagnosis the fault condition. PdM, knowing when to trigger maintenance action, is achieved through predicting the overall quality of the produced parts from the feature set extracted from sensor data of the Spark-out segment of the grinding cycle. Combining fault diagnosis with the predicted quality information resulted in reliable and actionable maintenance decisions for the bearing ring grinder. The demonstrated setup, based on a production bearing ring grinder, is adaptable to similar machines in production.
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