| 1. |
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| 2. |
- Aartsen, M. G., et al.
(författare)
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The IceCube Neutrino Observatory : instrumentation and online systems
- 2017
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Ingår i: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- The IceCube Neutrino Observatory is a cubic-kilometer-scale high-energy neutrino detector built into the ice at the South Pole. Construction of IceCube, the largest neutrino detector built to date, was completed in 2011 and enabled the discovery of high-energy astrophysical neutrinos. We describe here the design, production, and calibration of the IceCube digital optical module (DOM), the cable systems, computing hardware, and our methodology for drilling and deployment. We also describe the online triggering and data filtering systems that select candidate neutrino and cosmic ray events for analysis. Due to a rigorous pre-deployment protocol, 98.4% of the DOMs in the deep ice are operating and collecting data. IceCube routinely achieves a detector uptime of 99% by emphasizing software stability and monitoring. Detector operations have been stable since construction was completed, and the detector is expected to operate at least until the end of the next decade.
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| 3. |
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| 5. |
- Metcalfe, N. B., et al.
(författare)
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Solving the conundrum of intra-specific variation in metabolic rate: A multidisciplinary conceptual and methodological toolkit New technical developments are opening the door to an understanding of why metabolic rate varies among individual animals of a species
- 2023
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Ingår i: Bioessays. - 0265-9247. ; 45:6
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Tidskriftsartikel (refereegranskat)abstract
- Researchers from diverse disciplines, including organismal and cellular physiology, sports science, human nutrition, evolution and ecology, have sought to understand the causes and consequences of the surprising variation in metabolic rate found among and within individual animals of the same species. Research in this area has been hampered by differences in approach, terminology and methodology, and the context in which measurements are made. Recent advances provide important opportunities to identify and address the key questions in the field. By bringing together researchers from different areas of biology and biomedicine, we describe and evaluate these developments and the insights they could yield, highlighting the need for more standardisation across disciplines. We conclude with a list of important questions that can now be addressed by developing a common conceptual and methodological toolkit for studies on metabolic variation in animals.
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| 7. |
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| 8. |
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| 9. |
- Pettersen, Emily, 1996, et al.
(författare)
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Regenerative Peripheral Nerve Interface: Surgical Protocol for a Randomized Controlled Trial in Postamputation Pain
- 2024
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Ingår i: JOVE-JOURNAL OF VISUALIZED EXPERIMENTS. - 1940-087X. ; :205
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Tidskriftsartikel (refereegranskat)abstract
- Surgical procedures, including nerve reconstruction and end -organ muscle reinnervation, have become more prominent in the prosthetic field over the past decade. Primarily developed to increase the functionality of prosthetic limbs, these surgical procedures have also been found to reduce postamputation neuropathic pain. Today, some of these procedures are performed more frequently for the management and prevention of postamputation pain than for prosthetic fitting, indicating a significant need for effective solutions to postamputation pain. One notable emerging procedure in this context is the Regenerative Peripheral Nerve Interface (RPNI). RPNI surgery involves an operative approach that entails splitting the nerve end longitudinally into its main fascicles and implanting these fascicles within free denervated and devascularized muscle grafts. The RPNI procedure takes a proactive stance in addressing freshly cut nerve endings, facilitating painful neuroma prevention and treatment by enabling the nerve to regenerate and innervate an end organ, i.e., the free muscle graft. Retrospective studies have shown RPNI's effectiveness in alleviating postamputation pain and preventing the formation of painful neuromas. The increasing frequency of utilization of this approach has also given rise to variations in the technique. This article aims to provide a step-by-step description of the RPNI procedure, which will serve as the standardized procedure employed in an international, randomized controlled trial (ClinicalTrials.gov, NCT05009394). In this trial, RPNI is compared to two other surgical procedures for postamputation pain management, specifically, Targeted Muscle Reinnervation (TMR) and neuroma excision coupled with intra-muscular transposition and burying.
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| 10. |
- Zeggini, Eleftheria, et al.
(författare)
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Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:5, s. 638-645
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D)(1-11). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and similar to 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P=5.0 x 10(-14)), CDC123-CAMK1D (P=1.2 x 10(-10)), TSPAN8-LGR5 (P=1.1 x 10(-9)), THADA (P=1.1 x 10(-9)), ADAMTS9 (P=1.2 x 10(-8)) and NOTCH2 (P=4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.
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| 11. |
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| 13. |
- Feng, Xiaoshuang, et al.
(författare)
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Lung cancer risk discrimination of prediagnostic proteomics measurements compared with existing prediction tools
- 2023
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 115:9, s. 1050-1059
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We sought to develop a proteomics-based risk model for lung cancer and evaluate its risk-discriminatory performance in comparison with a smoking-based risk model (PLCOm2012) and a commercially available autoantibody biomarker test.METHODS: We designed a case-control study nested in 6 prospective cohorts, including 624 lung cancer participants who donated blood samples at most 3 years prior to lung cancer diagnosis and 624 smoking-matched cancer free participants who were assayed for 302 proteins. We used 470 case-control pairs from 4 cohorts to select proteins and train a protein-based risk model. We subsequently used 154 case-control pairs from 2 cohorts to compare the risk-discriminatory performance of the protein-based model with that of the Early Cancer Detection Test (EarlyCDT)-Lung and the PLCOm2012 model using receiver operating characteristics analysis and by estimating models' sensitivity. All tests were 2-sided.RESULTS: The area under the curve for the protein-based risk model in the validation sample was 0.75 (95% confidence interval [CI] = 0.70 to 0.81) compared with 0.64 (95% CI = 0.57 to 0.70) for the PLCOm2012 model (Pdifference = .001). The EarlyCDT-Lung had a sensitivity of 14% (95% CI = 8.2% to 19%) and a specificity of 86% (95% CI = 81% to 92%) for incident lung cancer. At the same specificity of 86%, the sensitivity for the protein-based risk model was estimated at 49% (95% CI = 41% to 57%) and 30% (95% CI = 23% to 37%) for the PLCOm2012 model.CONCLUSION: Circulating proteins showed promise in predicting incident lung cancer and outperformed a standard risk prediction model and the commercialized EarlyCDT-Lung.
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| 14. |
- Guida, Florence, et al.
(författare)
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The blood metabolome of incident kidney cancer: A case-control study nested within the MetKid consortium
- 2021
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Ingår i: PLoS Medicine. - : Public Library of Science (PLOS). - 1549-1277 .- 1549-1676. ; 18:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Excess bodyweight and related metabolic perturbations have been implicated in kidney cancer aetiology, but the specific molecular mechanisms underlying these relationships are poorly understood. In this study, we sought to identify circulating metabolites that predispose kidney cancer and to evaluate the extent to which they are influenced by body mass index (BMI).Methods and findings: We assessed the association between circulating levels of 1,416 metabolites and incident kidney cancer using pre-diagnostic blood samples from up to 1,305 kidney cancer case–control pairs from 5 prospective cohort studies. Cases were diagnosed on average 8 years after blood collection. We found 25 metabolites robustly associated with kidney cancer risk. In particular, 14 glycerophospholipids (GPLs) were inversely associated with risk, including 8 phosphatidylcholines (PCs) and 2 plasmalogens. The PC with the strongest association was PC ae C34:3 with an odds ratio (OR) for 1 standard deviation (SD) increment of 0.75 (95% confidence interval [CI]: 0.68 to 0.83, p = 2.6 × 10−8). In contrast, 4 amino acids, including glutamate (OR for 1 SD = 1.39, 95% CI: 1.20 to 1.60, p = 1.6 × 10−5), were positively associated with risk. Adjusting for BMI partly attenuated the risk association for some—but not all—metabolites, whereas other known risk factors of kidney cancer, such as smoking and alcohol consumption, had minimal impact on the observed associations. A mendelian randomisation (MR) analysis of the influence of BMI on the blood metabolome highlighted that some metabolites associated with kidney cancer risk are influenced by BMI. Specifically, elevated BMI appeared to decrease levels of several GPLs that were also found inversely associated with kidney cancer risk (e.g., −0.17 SD change [ßBMI] in 1-(1-enyl-palmitoyl)-2-linoleoyl-GPC (P-16:0/18:2) levels per SD change in BMI, p = 3.4 × 10−5). BMI was also associated with increased levels of glutamate (ßBMI: 0.12, p = 1.5 × 10−3). While our results were robust across the participating studies, they were limited to study participants of European descent, and it will, therefore, be important to evaluate if our findings can be generalised to populations with different genetic backgrounds.Conclusions: This study suggests a potentially important role of the blood metabolome in kidney cancer aetiology by highlighting a wide range of metabolites associated with the risk of developing kidney cancer and the extent to which changes in levels of these metabolites are driven by BMI - the principal modifiable risk factor of kidney cancer.
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| 15. |
- Halvorsen, A., et al.
(författare)
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Epidemiology of traumatic spinal cord injury in Norway in 2012-2016: a registry-based cross-sectional study
- 2019
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Ingår i: Spinal Cord. - : Springer Science and Business Media LLC. - 1362-4393 .- 1476-5624. ; 57:4, s. 331-338
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Tidskriftsartikel (refereegranskat)abstract
- Study design A registry-based cross-sectional study. Objectives To analyse the epidemiological and demographic characteristics of persons with traumatic spinal cord injury (TSCI) in Norway. Setting TSCI patients admitted for primary rehabilitation to one of the three specialised spinal cord injury (SCI) departments (located in Bergen, Trondheim, and Oslo) and consented to the Norwegian Spinal Cord Injury Registry (NorSCIR). Methods Analysis of data from NorSCIR during a 5-year period (2012-2016) was performed. Data were collected by using the International SCI Core Data Set as recommended by the International Spinal Cord Society (ISCoS). Results The lowest incidence of TSCI was 11.4/million (2012), and the highest incidence was 15.9/million (2014). In the study period, 349 individuals were registered with TSCI. In total, 76% were male, and the mean age was 47 (SD +/- 19) years. We observed dominance in the 60-74 years age group. The distribution between tetraplegia and paraplegia was 48%/42%. For those initially classified as American Spinal Cord Injury Association Impairment Scale (AIS) grade A (complete injury), 77% remained grade A at discharge. Considerable changes during primary rehabilitation after incomplete lesions were observed. Most patients (68%) were discharged home after primary rehabilitation. Falls were the main cause of TSCI (47%) and occurred more often during the weekend. Conclusion Through a National Medical Quality Registry based on internationally provided data sets, we are able to present systematic and updated data from Norway.
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| 16. |
- Halvorsen, A., et al.
(författare)
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Non-traumatic spinal cord injury in Norway 2012-2016: analysis from a national registry and comparison with traumatic spinal cord injury
- 2019
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Ingår i: Spinal Cord. - : Springer Science and Business Media LLC. - 1362-4393 .- 1476-5624. ; 57:4, s. 324-330
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Tidskriftsartikel (refereegranskat)abstract
- Study design Registry-based cross-sectional study. Objectives To describe and analyze epidemiological and demographic characteristics of non-traumatic spinal cord injury (NTSCI) and to compare persons with NTSCI and traumatic spinal cord injury (TSCI). Setting A total of 225 non-traumatic and 349 traumatic SCI patients were admitted for primary rehabilitation at one of the three specialized SCI departments in Norway (located in Bergen, Trondheim, and Oslo) from 2012 to 2016. Patients who consented to registration in the Norwegian Spinal Cord Injury Registry (NorSCIR) were included. Methods Data were collected using the International SCI Core Data Set, as recommended by the International Spinal Cord Society (ISCoS). Demographics and injury characteristics were analyzed descriptively. The NTSCI and TSCI groups were compared using a Mann-Whitney U test and chi-square test. Results The mean age of the NTSCI patients was 55 years, and 59% were male. The incidence of NTSCI was 7.7-10.4 per million person-years, which is lower than the incidence of TSCI. NTSCI individuals were older, less severely injured, and their length of stay at the hospital was shorter than the TSCI individuals. The results may be influenced by the inclusion criterion in the registry. This makes the analyzed sample for NTSCI less complete. However, the majority of patients with non-progressive NTSCI are included in the NorSCIR. Conclusion For the first time, we are able to provide the national epidemiological status on NTSCI based on available data from the national registry. Further studies are required to improve the capture of NTSCI for future incidence studies.
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| 17. |
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| 18. |
- Loeber, JG, et al.
(författare)
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Neonatal Screening in Europe Revisited: An ISNS Perspective on the Current State and Developments Since 2010
- 2021
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Ingår i: International journal of neonatal screening. - : MDPI AG. - 2409-515X. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Neonatal screening (NBS) was initiated in Europe during the 1960s with the screening for phenylketonuria. The panel of screened disorders (“conditions”) then gradually expanded, with a boost in the late 1990s with the introduction of tandem mass spectrometry (MS/MS), making it possible to screen for 40–50 conditions using a single blood spot. The most recent additions to screening programmes (screening for cystic fibrosis, severe combined immunodeficiency and spinal muscular atrophy) were assisted by or realised through the introduction of molecular technologies. For this survey, we collected data from 51 European countries. We report the developments between 2010 and 2020 and highlight the achievements reached with the progress made in this period. We also identify areas where further progress can be made, mainly by exchanging knowledge and learning from experiences in neighbouring countries. Between 2010 and 2020, most NBS programmes in geographical Europe matured considerably, both in terms of methodology (modernised) and with regard to the panel of conditions screened (expanded). These developments indicate that more collaboration in Europe through European organisations is gaining momentum. We can only accomplish the timely detection of newborn infants potentially suffering from one of the many rare diseases and take appropriate action by working together.
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| 19. |
- Midttun, Øivind, et al.
(författare)
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A cross-sectional study of inflammatory markers as determinants of circulating kynurenines in the Lung Cancer Cohort Consortium
- 2023
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Circulating concentrations of metabolites (collectively called kynurenines) in the kynurenine pathway of tryptophan metabolism increase during inflammation, particularly in response to interferon-gamma (IFN-γ). Neopterin and the kynurenine/tryptophan ratio (KTR) are IFN-γ induced inflammatory markers, and together with C-reactive protein (CRP) and kynurenines they are associated with various diseases, but comprehensive data on the strength of associations of inflammatory markers with circulating concentrations of kynurenines are lacking. We measured circulating concentrations of neopterin, CRP, tryptophan and seven kynurenines in 5314 controls from 20 cohorts in the Lung Cancer Cohort Consortium (LC3). The associations of neopterin, KTR and CRP with kynurenines were investigated using regression models. In mixed models, one standard deviation (SD) higher KTR was associated with a 0.46 SD higher quinolinic acid (QA), and 0.31 SD higher 3-hydroxykynurenine (HK). One SD higher neopterin was associated with 0.48, 0.44, 0.36 and 0.28 SD higher KTR, QA, kynurenine and HK, respectively. KTR and neopterin respectively explained 24.1% and 16.7% of the variation in QA, and 11.4% and 7.5% of HK. CRP was only weakly associated with kynurenines in regression models. In summary, QA was the metabolite that was most strongly associated with the inflammatory markers. In general, the inflammatory markers were most strongly related to metabolites located along the tryptophan-NAD axis, which may support suggestions of increased production of NAD from tryptophan during inflammation.
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| 20. |
- Pettersen, A. K., et al.
(författare)
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Population divergence in maternal investment and embryo energy use and allocation suggests adaptive responses to cool climates
- 2023
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Ingår i: Journal of Animal Ecology. - 0021-8790. ; 92:9, s. 1771-1785
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Tidskriftsartikel (refereegranskat)abstract
- The thermal sensitivity of early life stages can play a fundamental role in constraining species distributions. For egg-laying ectotherms, cool temperatures often extend development time and exacerbate developmental energy cost. Despite these costs, egg laying is still observed at high latitudes and altitudes. How embryos overcome the developmental constraints posed by cool climates is crucial knowledge for explaining the persistence of oviparous species in such environments and for understanding thermal adaptation more broadly. Here, we studied maternal investment and embryo energy use and allocation in wall lizards spanning altitudinal regions, as potential mechanisms that enable successful development to hatching in cool climates. Specifically, we compared population-level differences in (1) investment from mothers (egg mass, embryo retention and thyroid yolk hormone concentration), (2) embryo energy expenditure during development, and (3) embryo energy allocation from yolk towards tissue. We found evidence that energy expenditure was greater under cool compared with warm incubation temperatures. Females from relatively cool regions did not compensate for this energetic cost of development by producing larger eggs or increasing thyroid hormone concentration in yolk. Instead, embryos from the high-altitude region used less energy to complete development, that is, they developed faster without a concomitant increase in metabolic rate, compared with those from the low-altitude region. Embryos from high altitudes also allocated relatively more energy towards tissue production, hatching with lower residual yolk: tissue ratios than low-altitude region embryos. These results are consistent with local adaptation to cool climate and suggest that this is underpinned by mechanisms that regulate embryonic utilisation of yolk reserves and its allocation towards tissue, rather than shifts in maternal investment of yolk content or composition.
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| 21. |
- Pettersen, Emily, 1996, et al.
(författare)
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Targeted Muscle Reinnervation: Surgical Protocol for a Randomized Controlled Trial in Postamputation Pain
- 2024
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Ingår i: Journal of Visualized Experiments. - 1940-087X. ; 2024:205
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Tidskriftsartikel (refereegranskat)abstract
- Over the past decade, the field of prosthetics has witnessed significant progress, particularly in the development of surgical techniques to enhance the functionality of prosthetic limbs. Notably, novel surgical interventions have had an additional positive outcome, as individuals with amputations have reported neuropathic pain relief after undergoing such procedures. Subsequently, surgical techniques have gained increased prominence in the treatment of postamputation pain, including one such surgical advancement-targeted muscle reinnervation (TMR). TMR involves a surgical approach that reroutes severed nerves as a type of nerve transfer to "target" motor nerves and their accompanying motor end plates within nearby muscles. This technique originally aimed to create new myoelectric sites for amplified electromyography (EMG) signals to enhance prosthetic intuitive control. Subsequent work showed that TMR also could prevent the formation of painful neuromas as well as reduce postamputation neuropathic pain (e.g., Residual and Phantom Limb Pain). Indeed, multiple studies have demonstrated TMR's effectiveness in mitigating postamputation pain as well as improving prosthetic functional outcomes. However, technical variations in the procedure have been identified as it is adopted by clinics worldwide. The purpose of this article is to provide a detailed step-by-step description of the TMR procedure, serving as the foundation for an international, randomized controlled trial (ClinicalTrials.gov, NCT05009394), including nine clinics in seven countries. In this trial, TMR and two other surgical techniques for managing postamputation pain will be evaluated.
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| 22. |
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| 23. |
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| 24. |
- Rowe, AD, et al.
(författare)
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A Novel Approach to Improve Newborn Screening for Congenital Hypothyroidism by Integrating Covariate-Adjusted Results of Different Tests into CLIR Customized Interpretive Tools
- 2021
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Ingår i: International journal of neonatal screening. - : MDPI AG. - 2409-515X. ; 7:2
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Tidskriftsartikel (refereegranskat)abstract
- Newborn screening for congenital hypothyroidism remains challenging decades after broad implementation worldwide. Testing protocols are not uniform in terms of targets (TSH and/or T4) and protocols (parallel vs. sequential testing; one or two specimen collection times), and specificity (with or without collection of a second specimen) is overall poor. The purpose of this retrospective study is to investigate the potential impact of multivariate pattern recognition software (CLIR) to improve the post-analytical interpretation of screening results. Seven programs contributed reference data (N = 1,970,536) and two sets of true (TP, N = 1369 combined) and false (FP, N = 15,201) positive cases for validation and verification purposes, respectively. Data were adjusted for age at collection, birth weight, and location using polynomial regression models of the fifth degree to create three-dimensional regression surfaces. Customized Single Condition Tools and Dual Scatter Plots were created using CLIR to optimize the differential diagnosis between TP and FP cases in the validation set. Verification testing correctly identified 446/454 (98%) of the TP cases, and could have prevented 1931/5447 (35%) of the FP cases, with variable impact among locations (range 4% to 50%). CLIR tools either as made here or preferably standardized to the recommended uniform screening panel could improve performance of newborn screening for congenital hypothyroidism.
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| 25. |
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| 26. |
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| 27. |
- Tangeraas, T, et al.
(författare)
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Performance of Expanded Newborn Screening in Norway Supported by Post-Analytical Bioinformatics Tools and Rapid Second-Tier DNA Analyses
- 2020
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Ingår i: International journal of neonatal screening. - : MDPI AG. - 2409-515X. ; 6:3, s. 51-
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Tidskriftsartikel (refereegranskat)abstract
- In 2012, the Norwegian newborn screening program (NBS) was expanded (eNBS) from screening for two diseases to that for 23 diseases (20 inborn errors of metabolism, IEMs) and again in 2018, to include a total of 25 conditions (21 IEMs). Between 1 March 2012 and 29 February 2020, 461,369 newborns were screened for 20 IEMs in addition to phenylketonuria (PKU). Excluding PKU, there were 75 true-positive (TP) (1:6151) and 107 (1:4311) false-positive IEM cases. Twenty-one percent of the TP cases were symptomatic at the time of the NBS results, but in two-thirds, the screening result directed the exact diagnosis. Eighty-two percent of the TP cases had good health outcomes, evaluated in 2020. The yearly positive predictive value was increased from 26% to 54% by the use of the Region 4 Stork post-analytical interpretive tool (R4S)/Collaborative Laboratory Integrated Reports 2.0 (CLIR), second-tier biochemical testing and genetic confirmation using DNA extracted from the original dried blood spots. The incidence of IEMs increased by 46% after eNBS was introduced, predominantly due to the finding of attenuated phenotypes. The next step is defining which newborns would truly benefit from screening at the milder end of the disease spectrum. This will require coordinated international collaboration, including proper case definitions and outcome studies.
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| 28. |
- Tikkanen, T, et al.
(författare)
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Curriculum in kindergarten? : Literacy learning and use of ICT with small children
- 2013
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Ingår i: 23rd EECERA Conference: Values, Culture and Contexts. ; , s. 80-81
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Research aims: Mapping of (i) the status of the “kindergarten curriculum” in the participating countries in terms of policies, attitudes and practice in the area of early literacy learning, and the use of ICT to this end; (ii) the job competence of the pedagogical staff in kindergartens in the above regards.Relationship to previous research works: Relevant research from all five participating countries has contributed to building of the survey. For example studies on children’s play with and exploration of digital tools (digital photos, tablet PC) (Bølgan, 2009b; Jernes, Alvestad, & Sinnerud, 2010; Knudsen & Eriksen Ødegaard, 2011), on use of and access to digital tools (Bølgan, 2009), on children’s activity with a PC (DIGOB - Engelsen, Jernes, Kvinge, Vangsnes,& Økland, 2012), and on how to integrate digital tools in a play-based curriculum in kindergartens (Siraj-Blatchford, 2006) and on how children use social media and tablet pc (Kamp, 2013).Theoretical and conceptual framework: The work builds on a social-constructivist and socio-cultural theories on learning.Paradigm, methodology and methods: The study is based on an electronic survey, carried out in April 2013 in all countries participating in CHILDICT. A convenience sample was used.Ethical considerations: None.Main finding or discussion: The findings from the survey are not yet available. They will be compared across the participating countries. The discussion will be based on reflections from each country.Implications, practice or policy: To Teacher Training Institutions, local authorities, kindergartens, and further research.
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| 29. |
- Zahed, Hana, et al.
(författare)
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Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults
- 2021
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Imbalances of blood biomarkers are associated with disease, and biomarkers may also vary non-pathologically across population groups. We described variation in concentrations of biomarkers of one-carbon metabolism, vitamin status, inflammation including tryptophan metabolism, and endothelial and renal function among cancer-free older adults. We analyzed 5167 cancer-free controls aged 40–80 years from 20 cohorts in the Lung Cancer Cohort Consortium (LC3). Centralized biochemical analyses of 40 biomarkers in plasma or serum were performed. We fit multivariable linear mixed effects models to quantify variation in standardized biomarker log-concentrations across four factors: age, sex, smoking status, and body mass index (BMI). Differences in most biomarkers across most factors were small, with 93% (186/200) of analyses showing an estimated difference lower than 0.25 standard-deviations, although most were statistically significant due to large sample size. The largest difference was for creatinine by sex, which was − 0.91 standard-deviations lower in women than men (95%CI − 0.98; − 0.84). The largest difference by age was for total cysteine (0.40 standard-deviation increase per 10-year increase, 95%CI 0.36; 0.43), and by BMI was for C-reactive protein (0.38 standard-deviation increase per 5-kg/m2 increase, 95%CI 0.34; 0.41). For 31 of 40 markers, the mean difference between current and never smokers was larger than between former and never smokers. A statistically significant (p < 0.05) association with time since smoking cessation was observed for 8 markers, including C-reactive protein, kynurenine, choline, and total homocysteine. We conclude that most blood biomarkers show small variations across demographic characteristics. Patterns by smoking status point to normalization of multiple physiological processes after smoking cessation.
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| 30. |
- Bargheet, A., et al.
(författare)
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Development of early life gut resistome and mobilome across gestational ages and microbiota-modifying treatments
- 2023
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Ingår i: Ebiomedicine. - 2352-3964. ; 92
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Tidskriftsartikel (refereegranskat)abstract
- Background Gestational age (GA) and associated level of gastrointestinal tract maturation are major factors driving the initial gut microbiota composition in preterm infants. Besides, compared to term infants, premature infants often receive antibiotics to treat infections and probiotics to restore optimal gut microbiota. How GA, antibiotics, and probiotics modulate the microbiota’s core characteristics, gut resistome and mobilome, remains nascent. Methods We analysed metagenomic data from a longitudinal observational study in six Norwegian neonatal intensive care units to describe the bacterial microbiota of infants of varying GA and receiving different treatments. The cohort consisted of probiotic-supplemented and antibiotic-exposed extremely preterm infants (n = 29), antibiotic-exposed very preterm (n = 25), antibiotic-unexposed very preterm (n = 8), and antibiotic-unexposed full-term (n = 10) infants. The stool samples were collected on days of life 7, 28, 120, and 365, and DNA extraction was followed by shotgun metagenome sequencing and bioinformatical analysis. Findings The top predictors of microbiota maturation were hospitalisation length and GA. Probiotic administration rendered the gut microbiota and resistome of extremely preterm infants more alike to term infants on day 7 and ameliorated GA-driven loss of microbiota interconnectivity and stability. GA, hospitalisation, and both microbiota-modifying treatments (antibiotics and probiotics) contributed to an elevated carriage of mobile genetic elements in preterm infants compared to term controls. Finally, Escherichia coli was associated with the highest number of antibiotic-resistance genes, followed by Klebsiella pneumoniae and Klebsiella aerogenes. Interpretation Prolonged hospitalisation, antibiotics, and probiotic intervention contribute to dynamic alterations in resistome and mobilome, gut microbiota characteristics relevant to infection risk.
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| 31. |
- Bendiksen, M., et al.
(författare)
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Application of the Copenhagen Soccer Test in high-level women players - locomotor activities, physiological response and sprint performance
- 2013
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Ingår i: Human Movement Science. - : Elsevier BV. - 0167-9457. ; 32:6, s. 1430-1442
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated the physiological response, sprint performance and technical ability in various phases of the Copenhagen Soccer Test for Women (CSTw.) and investigated whether the locomotor activities of the CSTw were comparable to competitive match-play (CM). Physiological measurements and physical/technical assessments were performed during CSTw for eleven Norwegian high-level women soccer players. The activity pattern during CSTw and CM was monitored using the ZXY tracking system. No differences were observed between CSTw and CM with regards to total distance covered (10093 +/- 94 and 9674 +/- 191 m), high intensity running (1278 +/- 67 and 1193 +/- 115 m) or sprinting (422 +/- 55 and 372 +/- 46 m) (p > .05). During CSTw, average HR was 85 +/- 2%HRmax with 35 +/- 2% playing time >90%HRmax. Blood lactate increased (p < .05) from 1.4 +/- 0.3 mM at rest to an average of 4.7 +/- 0.5 mM during CSTw, with no changes during the test. Blood glucose was 5.4 +/- 0.3 mM at rest and remained unaltered during CSTw. Sprint performance (2 x 20 in) decreased (p < .05) by 3% during CSTw (8.19 +/- 0.06-8.47 +/- 0.10 s). In conclusion, the locomotor activities during CSTw were comparable to that of high-level competitive match-play. The physiological demands of the CSTw were high, with no changes in heart rate, blood lactate or technical performance during the test, but a lowered sprint performance towards the end of the test. (C) 2013 Elsevier B.V. All rights reserved.
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| 32. |
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| 33. |
- Finbråten, Hanne Søberg, 1972-, et al.
(författare)
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Validating the functional, communicative and critical health literacy scale using rasch modeling and confirmatory factor analysis
- 2018
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Ingår i: Journal of Nursing Measurement. - : Springer Publishing Company. - 1061-3749 .- 1945-7049. ; :2, s. 341-363
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: The functional, communicative, and critical health literacy (FCCHL) scale is widely used for assessing health literacy (HL) in people with chronic diseases, such as type 2 diabetes (T2DM). Despite related subscales, researchers continue to apply a consecutive modeling approach, treating the three subscales as independent. This article studies the psychometric characteristics of the FCCHL by applying multidimensional modeling approaches.Methods: Rasch modeling and confirmatory factor analyses were applied to responses (paper-and-pencil) from 386 adults with T2DM.Results: Using a six-point rating scale and a three-dimensional Rasch model, this study found that a 12-item version of the FCCHL reduced within-item bias and improved subscale reliability indexes.Conclusion: This study suggests a parsimonious 12-item version of the FCCHL. The data fit a three-dimensional Rasch model best.
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| 34. |
- Giordanetto, Fabrizio, et al.
(författare)
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Design of Selective sPLA2-X Inhibitor (-)-2-{2-[Carbamoyl-6-(trifluoromethoxy)-1 H-indol-1-yl]pyridine-2-yl}propanoic Acid
- 2018
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Ingår i: ACS Medicinal Chemistry Letters. - : American Chemical Society. - 1948-5875. ; 9:7, s. 600-605
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Tidskriftsartikel (refereegranskat)abstract
- A lead generation campaign identified indole-based sPLA2-X inhibitors with a promising selectivity profile against other sPLA2 isoforms. Further optimization of sPLA2 selectivity and metabolic stability resulted in the design of (-)-17, a novel, potent, and selective sPLA2-X inhibitor with an exquisite pharmacokinetic profile characterized by high absorption and low clearance, and low toxicological risk. Compound (-)-17 was tested in an ApoE-/- murine model of atherosclerosis to evaluate the effect of reversible, pharmacological sPLA2-X inhibition on atherosclerosis development. Despite being well tolerated and achieving adequate systemic exposure of mechanistic relevance, (-)-17 did not significantly affect circulating lipid and lipoprotein biomarkers and had no effect on coronary function or histological markers of atherosclerosis.
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| 35. |
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| 36. |
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| 37. |
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| 38. |
- Johnsen, JI, et al.
(författare)
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NSAIDs in neuroblastoma therapy
- 2005
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Ingår i: Cancer letters. - : Elsevier BV. - 0304-3835. ; 228:1-2, s. 195-201
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Tidskriftsartikel (refereegranskat)
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| 39. |
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| 40. |
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| 41. |
- Lehmann, Fredrik, 1976, et al.
(författare)
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Novel potent and efficacious nonpeptidic urotensin II receptor agonists
- 2006
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 49, s. 2232-2240
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Tidskriftsartikel (refereegranskat)abstract
- Six different series of nonpeptidic urotensin II receptor agonists have been synthesized and evaluated for their agonistic activity in a cell-based assay (R-SAT). The compounds are ring-opened analogues of the isochromanone-based agonist AC-7954 with different functionalities constituting the linker between the two aromatic ring moieties. Several of the compounds are highly potent and efficacious, with N-[1-(4-chlorophenyl)-3-(dimethylamino)- propyl]-4-phenylbenzamide oxalate (5d) being the most potent. The pure enantiomers of 5d were obtained from the corresponding diastereomeric amides. It was shown by a combination of X-ray crystallography and chemical correlation that the activity resides in the S-enantiomer of 5d (pEC50 7.49). © 2006 American Chemical Society.
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| 42. |
- Ljungblad, Ulf Wike, et al.
(författare)
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The prevalence and clinical relevance of hyperhomocysteinemia suggesting vitamin B12 deficiency in presumed healthy infants
- 2021
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Ingår i: European Journal of Paediatric Neurology. - : Elsevier BV. - 1090-3798. ; 35, s. 137-146
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous studies have demonstrated a high prevalence of biochemical vitamin B12 deficiency in infants in Norway. Increased total homocysteine (tHcy) is the most important marker of B12 deficiency in infants. There is a need to evaluate its clinical relevance. Aims: To investigate the prevalence of hyperhomocysteinemia (S-tHcy > 8 μmol/L) suggestive of suboptimal B12 status and the prevalence of clinically relevant hyperhomocysteinemia in presumed healthy infants in Norway. Further, to evaluate risk factors, presence of symptoms and psychomotor development in these children. Methods: In a prospective study we clinically examined 252 infants aged 3–7 months using standardized neurological and psychomotor tests prior to analyzing biochemical B12 deficiency markers in 250 infants. Results: Twenty-five of 250 (10%) infants had hyperhomocysteinemia combined with clinically relevant symptoms suggestive of B12 deficiency. Hyperhomocysteinemia was associated with tremor, excessive sleep, and sub-normal scores in the fine motor section of the Ages and Stages Questionnaire. One-hundred and fourteen of 250 (46%) infants had hyperhomocysteinemia. Multiple regression analysis showed months of infant formula use as the strongest negative predictor for hyperhomocysteinemia. Conclusion: We have demonstrated associations between symptoms suggestive of infant B12 deficiency and increased levels of tHcy in presumed healthy infants The combination of hyperhomocysteinemia and associated relevant symptoms suggestive of B12 deficiency was a common finding, albeit most infants with hyperhomocysteinemia did not show symptoms.
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| 43. |
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| 44. |
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| 45. |
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| 46. |
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| 47. |
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| 48. |
- Pettersen, Emily, 1996, et al.
(författare)
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Enhancing osteoblast survival through pulsed electrical stimulation and implications for osseointegration
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Electrical stimulation has been suggested as a means for promoting the direct structural and functional bonding of bone tissue to an artificial implant, known as osseointegration. Previous work has investigated the impact of electrical stimulation in different models, both in vitro and in vivo, using various electrode configurations for inducing an electric field with a wide range of stimulation parameters. However, there is no consensus on optimal electrode configuration nor stimulation parameters. Here, we investigated a novel approach of delivering electrical stimulation to a titanium implant using parameters clinically tested in a different application, namely peripheral nerve stimulation. We propose an in vitro model comprising of Ti6Al4V implants precultured with MC3T3-E1 preosteoblasts, stimulated for 72 h at two different pulse amplitudes (10 mu A and 20 mu A) and at two different frequencies (50 Hz and 100 Hz). We found that asymmetric charge-balanced pulsed electrical stimulation improved cell survival and collagen production in a dose-dependent manner. Our findings suggest that pulsed electrical stimulation with characteristics similar to peripheral nerve stimulation has the potential to improve cell survival and may provide a promising approach to improve peri-implant bone healing, particularly to neuromusculoskeletal interfaces in which implanted electrodes are readily available.
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| 49. |
- Pettersen, I., et al.
(författare)
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Expression of TWEAK/Fn14 in neuroblastoma: Implications in tumorigenesis
- 2013
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Ingår i: International Journal of Oncology. - : Spandidos Publications. - 1019-6439 .- 1791-2423. ; 42:4, s. 1239-1248
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Tidskriftsartikel (refereegranskat)abstract
- Tumor necrosis factor-like weak inducer of apoptosis (TWEAK), a member of the tumor necrosis factor (TNF) family of cytokines, acts on responsive cells via binding to a cell surface receptor called Fn14. TWEAK binding to an Fn14 receptor or constitutive Fn14 overexpression has been shown to activate nuclear factor κB signaling which is important in tumorigenesis and cancer therapy resistance. In the present study, we demonstrate that TWEAK and Fn14 are expressed in neuroblastoma cell lines and primary tumors, and both are observed at increased levels in high-stage tumors. The treatment of neuroblastoma cell lines with recombinant TWEAK in vitro causes increased survival, and this effect is partially due to the activation of NF-κB signaling. Moreover, TWEAK induces the release of matrix metalloprotease-9 (MMP-9) in neuroblastoma cells, suggesting that TWEAK may play a role in the invasive phase of neuroblastoma tumorigenesis. TWEAK-induced cell survival was significantly reduced by silencing the TWEAK and Fn14 gene functions by siRNA. Thus, the expression of TWEAK and Fn14 in neuroblastoma suggests that TWEAK functions as an important regulator of primary neuroblastoma growth, invasion and survival and that the therapeutic intervention of the TWEAK/Fn14 pathway may be an important clinical strategy in neuroblastoma therapy.
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| 50. |
- Pettersen, S. A., et al.
(författare)
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Caffeine supplementation does not affect match activities and fatigue resistance during match play in young football players
- 2014
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Ingår i: Journal of Sports Sciences. - : Informa UK Limited. - 0264-0414 .- 1466-447X. ; 32:20, s. 1958-1965
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Tidskriftsartikel (refereegranskat)abstract
- The study examined the effect of caffeine supplementation on match activities and development of fatigue during a football match. In a randomised, double-blind cross-over design, two experimental football games separated by 7days were organised between the junior teams of two professional football clubs (17.6 +/- 1.1years (+/- s), 71.7 +/- 6.9kg, 13.9%+/- 5.0% body fat). The players ingested either a capsule of 6mg center dot kg(-1)b.w. caffeine or placebo (dextrose) 65min prior to the matches. Match activities were assessed using the ZXY match analysis system, and a Yo-Yo intermittent recovery test-level 2 (Yo-Yo IR2) was conducted immediately post-game. Heart rate was monitored throughout the game, and blood samples were obtained at baseline, half-time and after the game. There were no differences between caffeine and placebo regarding total distance covered (10,062 +/- 916 vs 9854 +/- 901m), high-intensity running (557 +/- 178 vs 642 +/- 240m), sprinting distance (109 +/- 58 vs 112 +/- 69m) or acceleration counts (123 +/- 31 vs 126 +/- 24). In both trials, players displayed lower (P<0.05) values in total distance and acceleration counts in the last 15min compared to all other 15-min periods of the matches. Post-game Yo-Yo IR2 performance was not different between game trials (caffeine: 829 +/- 322m; placebo 819 +/- 289m). In conclusion, oral caffeine administration does not appear to have an ergogenic effect in young football players during match play.
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