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1.
  • Jørgensen, Tanja Schjødt, et al. (författare)
  • Protocol for evaluating and implementing a pragmatic value-based healthcare management model for patients with inflammatory arthritis : A Danish population-based regional cohort and qualitative implementation study
  • 2018
  • Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 8:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction The provision of healthcare for patients with inflammatory arthritis occurs in the context of somewhat conflicting targets, values and drivers. Therefore, there is a need for introducing 'value-based healthcare' defined as the value of patient relevant health outcomes in relation to costs. This term is a central part of tomorrow's healthcare sector, especially for rheumatic diseases, yet the transition is a huge challenge, as it will impact the development, delivery and assessment of healthcare. Aims The aim of this study is to compare medical and patient evaluated impact of the traditional settlement and financing production (DAGS) controlled healthcare setting with a value-based and patient-centred adjunctive to standard care. Methods and analysis Patients with inflammatory arthritis receiving treatment in routine care at the outpatient clinics in the Capital Region of Denmark will prospectively and consecutively be enrolled in a Non-Intervention-Study framework providing a pragmatic value-based management model. A Danish reference cohort, used for comparison will be collected as part of routine clinical care. The enrolment period will be from 1 June 2018 until 31December 2023. Baseline and follow-up visits will be according to routine clinical care. Registry data will be obtained directly from patients and include personal, clinical and outcomes information. The study results will be reported in accordance with the STROBE statement. Ethics and dissemination The study has been notified to the Danish Data Protection Agency and granted authorisation for the period June 2018 to January 2025 (pending). Informed consent will be obtained from all patients before enrolment in the study. The study is approved by the ethics committee, Capital Region of Denmark (H-18013158). Results of the study will be disseminated through publication in international peer-reviewed journals.
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2.
  • Norsker, Filippa Nyboe, et al. (författare)
  • Neurologic disorders in long-term survivors of neuroblastoma–a population-based cohort study within the Adult Life after Childhood Cancer in Scandinavia (ALiCCS) research program
  • 2020
  • Ingår i: Acta Oncologica. - 0284-186X. ; 59:2, s. 134-140
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Neuroblastoma is the commonest extracranial solid tumor of childhood, yet rare, and with poor survival before 1990, especially for high-risk disease; thus, information on late effects is sparse. With great advances in cancer treatment, survival has reached 80% in the Nordic countries. The aim of the study was to investigate the risk of developing neurologic disorders after neuroblastoma. Material and methods: Through population-based cancer registries of four Nordic countries we identified 654 5-year survivors of neuroblastoma (diagnosed 1959–2008) and 133,668 matched population comparisons. We grouped neurologic diagnoses from national hospital registries into 11 main diagnostic categories and 56 disease-specific sub-categories and calculated relative risks (RRs), absolute excess risks (AERs), cumulative incidence and mean cumulative count (MCC). Information on cancer treatment was available for 49% of survivors. Results: A hospital contact for a neurologic disorder was observed in 181 survivors 5 years or more from cancer diagnosis with 59 expected, yielding a RR of 3.1 (95% CI 2.7–3.6) and an AER of 16 per 1,000 person-years (95% CI 12–19). The most frequent disorders included epilepsy, paralytic syndromes, diseases of the eyes and ears and hearing loss. The cumulative incidence of any neurologic disorder was 31% in survivors 20 years after cancer diagnosis with a MCC of 0.5 unique diagnoses. All risks were highest in survivors of high-risk neuroblastoma. Conclusion: Neuroblastoma survivors represent a population with a high risk of developing neurologic disorders. Our results should contribute to improving health care planning and underscores the need for systematic follow-up care of this vulnerable group of survivors.
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3.
  • Norsker, Filippa Nyboe, et al. (författare)
  • Risk of late health effects after soft-tissue sarcomas in childhood–a population-based cohort study within the Adult Life after Childhood Cancer in Scandinavia research programme
  • 2020
  • Ingår i: Acta Oncologica. - 0284-186X. ; 59:10, s. 1-11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In the 1960s only 1/3 of children with soft-tissue sarcomas survived, however with improved treatments survival today has reached 70%. Given the previous poor survival and the rarity of soft-tissue sarcomas, the risk of somatic late effects in a large cohort of Nordic soft-tissue sarcoma survivors has not yet been assessed. Methods: In this population-based cohort study we identified 985 five-year soft-tissue sarcoma survivors in Nordic nationwide cancer registries and late effects in national hospital registries covering the period 1964–2012. Information on tumour site and radiotherapy was available for Danish and Finnish survivors (N = 531). Using disease-specific rates of first-time hospital contacts for somatic diseases in survivors and in 4,830 matched comparisons we calculated relative rates (RR) and rate differences (RD). Results: Survivors had a RR of 1.5 (95% CI 1.4–1.7) and an absolute RD of 23.5 (17.7–29.2) for a first hospital contact per 1,000 person-years. The highest risks in both relative and absolute terms were of endocrine disorders (RR = 2.5; RD = 7.6), and diseases of the nervous system (RR = 1.9; RD = 6.6), digestive organs (RR = 1.7; RD = 5.4) and urinary system (RR = 1.7; RD = 5.6). By tumour site, excess risk was lower after extremity tumours. Irradiated survivors had a 2.6 (1.2–5.9) times higher risk than non-irradiated. Conclusions: Soft-tissue sarcoma survivors have an increased risk of somatic late effects in 5 out of 10 main diagnostic groups of diseases, and the risk remains increased up to 40 years after cancer diagnosis. Risks were slightly lower for those treated for tumours in the extremities, and radiotherapy increased the risk by more than two-fold.
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4.
  • Norsker, Filippa Nyboe, et al. (författare)
  • Somatic late effects in 5-year survivors of neuroblastoma : a population-based cohort study within the Adult Life after Childhood Cancer in Scandinavia study
  • 2018
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 143:12, s. 3083-3096
  • Tidskriftsartikel (refereegranskat)abstract
    • Because of the rarity of neuroblastoma and poor survival until the 1990s, information on late effects in neuroblastoma survivors is sparse. We comprehensively reviewed the long-term risk for somatic disease in neuroblastoma survivors. We identified 721 5-year survivors of neuroblastoma in Nordic population-based cancer registries and identified late effects in national hospital registries covering the period 1977–2012. Detailed treatment information was available for 46% of the survivors. The disease-specific rates of hospitalization of survivors and of 152,231 randomly selected population comparisons were used to calculate standardized hospitalization rate ratios (SHRRs) and absolute excess risks (AERs). During 5,500 person-years of follow-up, 501 5-year survivors had a first hospital contact yielding a SHRR of 2.3 (95% CI 2.1–2.6) and a corresponding AER of 52 (95% CI 44–60) per 1,000 person-years. The highest relative risks were for diseases of blood and blood-forming organs (SHRR 3.8; 95% CI 2.7–5.4), endocrine diseases (3.6 [3.1–4.2]), circulatory system diseases (3.1 [2.5–3.8]), and diseases of the nervous system (3.0 [2.6–3.3]). Approximately 60% of the excess new hospitalizations of survivors were for diseases of the nervous system, urinary system, endocrine system, and bone and soft tissue. The relative risks and AERs were highest for the survivors most intensively treated. Survivors of neuroblastoma have a highly increased long-term risk for somatic late effects in all the main disease groups as compared to background levels. Our results are useful for counseling survivors and should contribute to improving health care planning in post-therapy clinics.
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5.
  • Andersen, Mikkel Rathsach, et al. (författare)
  • Monoblock versus modular polyethylene insert in uncemented total knee arthroplasty : A randomized RSA study with 2-year follow-up of 53 patients
  • 2016
  • Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 87:6, s. 607-614
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose — Backside wear of the polyethylene insert in total knee arthroplasty (TKA) can produce clinically significant levels of polyethylene debris, which can lead to loosening of the tibial component. Loosening due to polyethylene debris could theoretically be reduced in tibial components of monoblock polyethylene design, as there is no backside wear. We investigated the effect of 2 different tibial component designs, monoblock and modular polyethylene, on migration of the tibial component in uncemented TKA. Patients and methods — In this randomized study, 53 patients (mean age 61 years), 32 in the monoblock group and 33 in the modular group, were followed for 2 years. Radiostereometric analysis (RSA) was done postoperatively after weight bearing and after 3, 6, 12, and 24 months. The primary endpoint of the study was comparison of the tibial component migration (expressed as maximum total point motion (MTPM)) of the 2 different implant designs. Results — We did not find any statistically significant difference in MTPM between the groups at 3 months (p = 0.2) or at 6 months (p = 0.1), but at 12 and 24 months of follow-up there was a significant difference in MTPM of 0.36 mm (p = 0.02) and 0.42 mm (p = 0.02) between groups, with the highest amount of migration (1.0 mm) in the modular group. The difference in continuous migration (MTPM from 12 and 24 months) between the groups was 0.096 mm (p = 0.5), and when comparing MTPM from 3–24 months, the difference between the groups was 0.23 mm (p = 0.07). Interpretation — In both study groups, we found the early migration pattern expected, with a relatively high initial amount of migration from operation to 3 months of follow-up, followed by stabilization of the implant with little migration thereafter. However, the modular implants had a statistically significantly higher degree of migration compared to the monoblock. We believe that the greater stiffness of the modular implants was the main reason for the difference in migration, but an initial creep in the polyethylene metal-back locking mechanism of the modular group could also be a possible explanation for the observed difference in migration between the 2 study groups.
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6.
  • Andersen, Mikkel Rathsach, et al. (författare)
  • Tibial Component Undersizing Is Related to High Degrees of Implant Migration Following Cementless Total Knee Arthroplasty : A Study of Radiostereometric Analysis Data for 111 Patients with 2-Year Follow-up
  • 2023
  • Ingår i: JBJS Open Access. - 2472-7245. ; 8:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Radiostereometric analysis (RSA) studies have shown that the continuous migration of tibial components is predictive of aseptic loosening following total knee arthroplasty (TKA). In the present study, we investigated whether accurate sizing and placement of tibial components are related to the degree of implant migration as measured with use of RSA.Methods:A total of 111 patients who underwent TKA surgery with a cementless tibial component were followed for a period of 2 years postoperatively, during which implant migration was assessed with use of RSA. RSA was performed within 7 days postoperatively and after 3, 6, 12, and 24 months. Postoperative radiographs were evaluated for component size and placement in the tibia. The evaluations were performed by experienced knee surgeons who were blinded to the migration data and clinical outcomes. A multivariable linear regression analysis was conducted.Results:Continuous implant migration (i.e., migration occurring between 12 and 24 months postoperatively) had a negative association with tibial component size (coefficient [B], -0.2; 95% confidence interval [CI], -0.33 to -0.08). Subsidence was associated with the absence of posterior cortical bone support (B, -0.7; 95% CI, -1.09 to -0.28), the absence of lateral cortical bone support (B, 0.8; 95% CI, 0.29 to 1.37), frontal-plane varus malalignment (B, 0.6; 95% CI, 0.12 to 1.16), and component undersizing (B, -0.4; 95% CI, -0.06 to -0.68). Posterior tilt was associated only with undersizing (B, 0.6; 95% CI, 0.27 to 1.11).Conclusions:Undersized cementless tibial components are at a higher risk for poor fixation with continuous migration following TKA. Therefore, a higher risk of aseptic loosening should be expected.Level of Evidence:Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
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7.
  • Angelcheva, Liudmila, et al. (författare)
  • Metabolomic analysis of extreme freezing tolerance in Siberian spruce (Picea obovata)
  • 2014
  • Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 204:3, s. 545-555
  • Tidskriftsartikel (refereegranskat)abstract
    • Siberian spruce (Picea obovata) is one of several boreal conifer species that can survive at extremely low temperatures (ELTs). When fully acclimated, its tissues can survive immersion in liquid nitrogen. Relatively little is known about the biochemical and biophysical strategies of ELT survival. We profiled needle metabolites using gas chromatography coupled with mass spectrometry (GC-MS) to explore the metabolic changes that occur during cold acclimation caused by natural temperature fluctuations. In total, 223 metabolites accumulated and 52 were depleted in fully acclimated needles compared with pre-acclimation needles. The metabolite profiles were found to develop in four distinct phases, which are referred to as pre-acclimation, early acclimation, late acclimation and fully acclimated. Metabolite changes associated with carbohydrate and lipid metabolism were observed, including changes associated with increased raffinose family oligosaccharide synthesis and accumulation, accumulation of sugar acids and sugar alcohols, desaturation of fatty acids, and accumulation of digalactosylglycerol. We also observed the accumulation of protein and nonprotein amino acids and polyamines that may act as compatible solutes or cryoprotectants. These results provide new insight into the mechanisms of freezing tolerance development at the metabolite level and highlight their importance in rapid acclimation to ELT in P.obovata.
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8.
  • Badawy, Mona, et al. (författare)
  • Hospital volume and the risk of revision in Oxford unicompartmental knee arthroplasty in the Nordic countries -an observational study of 14,496 cases
  • 2017
  • Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 18:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: High procedure volume and dedication to unicompartmental knee arthroplasty (UKA) has been suggested to improve revision rates. This study aimed to quantify the annual hospital volume effect on revision risk in Oxfordu? nicompartmental knee arthroplasty in the Nordic countries. Methods: 14,496 cases of cemented medial Oxford III UKA were identified in 126 hospitals in the four countries included in the Nordic Arthroplasty Register Association (NARA) database from 2000 to 2012. Hospitals were divided by quartiles into 4 annual procedure volume groups (≤11, 12-23, 24-43 and ≥44). The outcome was revision risk after 2 and 10 years calculated using Kaplan Meier method. Multivariate Cox regression analysis was used to assess the Hazard Ratio (HR) of any revision due to specific reasons with 95% confidence intervals (CI). Results: The implant survival was 80% at 10 years in the volume group ≤11 procedures per year compared to 83% in other volume groups. The HR adjusted for age category, sex, year of surgery and nation was 0.87 (95% CI: 0.76-0.99, p = 0.036) for the group 12-23 procedures per year, 0.78 (95% CI: 0.68-0.91, p = 0.002) for the group 24-43 procedures per year and 0.82 (95% CI: 0.70-0.94, p = 0.006) for the group ≥44 procedures per year compared to the low volume group. Log-rank test was p = 0.003. The risk of revision for unexplained pain was 40-50% higher in the low compared with other volume groups. Conclusion: Low volume hospitals performing ≤11 Oxford III UKAs per year were associated with an increased risk of revision compared to higher volume hospitals, and unexplained pain as revision cause was more common in low volume hospitals.
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11.
  • Fan, Xuge, et al. (författare)
  • Graphene ribbons with suspended masses as transducers in ultra-small nanoelectromechanical accelerometers
  • 2019
  • Ingår i: Nature Electronics. - : Nature Publishing Group. - 2520-1131. ; 2:9, s. 394-404
  • Tidskriftsartikel (refereegranskat)abstract
    • Nanoelectromechanical system (NEMS) sensors and actuators could be of use in the development of next-generation mobile, wearable and implantable devices. However, these NEMS devices require transducers that are ultra-small, sensitive and can be fabricated at low cost. Here, we show that suspended double-layer graphene ribbons with attached silicon proof masses can be used as combined spring–mass and piezoresistive transducers. The transducers, which are created using processes that are compatible with large-scale semiconductor manufacturing technologies, can yield NEMS accelerometers that occupy at least two orders of magnitude smaller die area than conventional state-of-the-art silicon accelerometers. With our devices, we also extract the Young’s modulus values of double-layer graphene and show that the graphene ribbons have significant built-in stresses.
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12.
  • Fischer, Andreas C., 1982-, et al. (författare)
  • Wafer-level integration of NiTi shape memory alloy wires for the fabrication of microactuators using standard wire bonding technology
  • 2011
  • Ingår i: 24th International Conference on Micro Electro Mechanical Systems (MEMS), 2011 IEEE. - : IEEE. ; , s. 348-351
  • Konferensbidrag (refereegranskat)abstract
    • This paper reports on the first integration of SMA wires into silicon based MEMS structures using a standard wire bonder. This approach allows fast and efficient placement, alignment and mechanical attachment of NiTi-based SMA wires to silicon-based MEMS. The wires are mechanically anchored and clamped into deep-etched silicon structures on a wafer. The placement precision is high with an average deviation of 4 #x03BC;m and the mechanical clamping is strong, allowing successful actuation of the SMA wires.
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13.
  • Fischer, Andreas C., 1982-, et al. (författare)
  • Wire-bonder-assisted integration of non-bondable SMA wires into MEMS substrates
  • 2012
  • Ingår i: Journal of Micromechanics and Microengineering. - : Institute of Physics Publishing (IOPP). - 0960-1317 .- 1361-6439. ; 22:5, s. 055025-
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper reports on a novel technique for the integration of NiTi shape memory alloy wires and other non-bondable wire materials into silicon-based microelectromechanical system structures using a standard wire-bonding tool. The efficient placement and alignment functions of the wire-bonding tool are used to mechanically attach the wire to deep-etched silicon anchoring and clamping structures. This approach enables a reliable and accurate integration of wire materials that cannot be wire bonded by traditional means.
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14.
  • Fors, Maria, et al. (författare)
  • Are illness perceptions and patient self-care enablement mediators of treatment effect in best practice physiotherapy low back pain care? Secondary mediation analyses in the BetterBack trial
  • 2023
  • Ingår i: Physiotherapy Theory and Practice. - : Taylor & Francis. - 0959-3985 .- 1532-5040. ; , s. 1-14
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: A best practice physiotherapy model of care (BetterBack MoC) for low back pain (LBP) aimed to improve patients' illness perceptions and self-care enablement, according to the Common-Sense Model of Self-Regulation (CSM).OBJECTIVE: To confirm if illness perceptions and patient self-care enablement, in line with the CSM, are mediators of treatment effects on disability and pain of the BetterBack MoC for patients with LBP compared to routine primary care. A secondary aim was to explore if illness perceptions and patient self-care enablement are mediators of guideline adherent care.METHODS: Pre-planned single mediation analyses tested whether hypothesized mediators at 3 months mediated the treatment effect of the MoC (n = 264) compared to routine care (n = 203) on disability and pain at 6 months. Secondary mediation analyses compared guideline adherent care with non-adherent care.RESULTS: No indirect effects were identified. The BetterBack intervention did not have superior effects over routine care on the hypothesized mediators. Illness perceptions and self-care enablement were significantly associated with disability and pain at 6 months. Secondary analyses showed significant indirect effects of guideline adherent care through tested mediators.CONCLUSION: Despite no indirect effects, patients' illness perceptions and self-care enablement were associated with disability and back pain intensity outcomes and are potentially relevant treatment targets.
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15.
  • Frost, Britt-Marie (författare)
  • Chemotherapy in Childhood Acute Lymphoblastic Leukemia : In vitro cellular drug resistance and pharmacokinetics
  • 2002
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The aims of the studies described in this thesis were to investigate the pharmacokinetics of and cellular resistance to chemotherapy as causes of treatment failure in childhood acute lymphoblastic leukemia (ALL).Leukemic cells from 370 children with newly diagnosed ALL were tested by the Fluorometric Microculture Cytotoxicity Assay to measure their resistance to each of ten standard cytotoxic drugs. In the high-risk group, increased in vitro resistance to each of the drugs dexamethasone, etoposide and doxorubicin was associated with a worse clinical outcome. Combining the results for these drugs yielded a drug resistance score, showing a relative risk of relapse in the most resistant group that was 9.8 times higher than in the most sensitive group. In the standard-risk and intermediate-risk groups, final evaluation must await longer follow-up.The new cytotoxic agent CHS 828 was equally active in vitro in samples from children with acute myeloblastic leukemia (AML) and ALL, with 50% cell kill at concentrations achievable in vivo. In AML samples CHS 828 also displayed high frequencies of synergistic interactions with four standard drugs. The well-known differences in clinical outcome between Down´s syndrome (DS) and non-DS children with acute leukemia may partly be explained by our finding of differences in drug resistance at the cellular level.Pharmacokinetic studies were performed at the start of induction treatment of ALL. Doxorubicin was assayed by reversed-phase liquid chromatography with fluorometric detection, and vincristine by high performance liquid chromatography with electrochemical detection. Plasma doxorubicin concentrations were measured in 107 children after 23 h of a 24-h infusion. The median steady-state concentration in children 4-6 years old, a group known to have a favorable outcome of treatment, was about 50% higher than in those 1-2 and >6 years old Vincristine pharmacokinetics was evaluated in 98 children. There was no correlation between age and total body clearance or any other pharmacokinetic parameters.In vitro testing of cellular drug resistance might be useful in predicting the outcome in high-risk ALL. The further exploration of CHS 828 in childhood leukemia seems warranted. There is no pharmacokinetic rationale for the common practice of administering relatively lower doses of vincristine to adolescents than to younger children.
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16.
  • Hess, Timo, et al. (författare)
  • Dissecting the genetic heterogeneity of gastric cancer
  • 2023
  • Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 92
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture.Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO.Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level.Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO. 
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17.
  • Holbech, Henrik, et al. (författare)
  • Estrogenic effect of the phytoestrogen biochanin A in zebrafish, Danio rerio, and brown trout, Salmo trutta.
  • 2013
  • Ingår i: Aquatic Toxicology. - : Elsevier BV. - 0166-445X .- 1879-1514. ; 144-145, s. 19-25
  • Tidskriftsartikel (refereegranskat)abstract
    • UNLABELLED: Isoflavones with estrogenic activity produced in Fabaceae plants are known to leach from agricultural areas to freshwater systems, but the effect of waterborne isoflavones in fish has not been thoroughly characterized. Therefore, the estrogenic effect of waterborne biochanin A was investigated in zebrafish (Danio rerio) and juvenile brown trout (Salmo trutta). Exposure of juvenile brown trout to 10 μg biochanin AL(-1) or higher caused marked vitellogenin induction after 9-10 days of exposure and so did exposure to 186 μg biochanin AL(-1) for 6h. Following 8d of exposure, a NOEC for induction of vitellogenin production in male zebrafish was 70 and LOEC 114 μg biochanin AL(-1). Exposure to 209 μg biochanin AL(-1) from hatch to 60 days post hatch (dph) caused a skewing of the sex ratio toward more phenotypic female zebrafish, but did not cause induction of vitellogenin in male and undifferentiated fish.IN CONCLUSION: (1) biochanin A elicits estrogenic effects in trout at environmentally realistic concentrations, (2) brown trout plasma vitellogenin concentrations respond to lower biochanin A exposure concentrations than vitellogenin concentrations in zebrafish homogenates and (3) concerning vitellogenin induction, the hypothesis should be tested if short term tests with zebrafish may show a higher sensitivity than partial life cycle tests.
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18.
  • Holm, Pætur Mikal, et al. (författare)
  • Intrarater Reliability and Agreement of Recommended Performance-Based Tests and Common Muscle Function Tests in Knee Osteoarthritis.
  • 2021
  • Ingår i: Journal of geriatric physical therapy (2001). - 2152-0895. ; 44:3, s. 144-152
  • Tidskriftsartikel (refereegranskat)abstract
    • Some uncertainty persists regarding the reproducibility of the recommended core set of performance-based tests, as well as common muscle function tests, when applied in individuals with knee osteoarthritis (KOA). The purpose of this study was to investigate the intrarater reliability and agreement of the recommended core set of performance-based tests and common muscle function tests in KOA.Participants (N=40) with radiographic and/or symptomatic KOA were evaluated twice with a 3-day interval between test sessions using the following tests: Leg extensor (LE) maximal muscle power measured in a Nottingham Power Rig; knee extensor (KE) peak isometric strength measured with a handheld dynamometer; 40-m walk test; 30-second chair-stand test; and 9-step stair climb test. Reliability was assessed using a 2-way, mixed-effects, single-measures model (3,1), absolute agreement-type intraclass correlation coefficient (ICC). Agreement was assessed using 95% limits of agreement (LOA) and LOA relative to the mean score from test and retest (LOA-%).Reliability for all tests was very high (ICC ≥ 0.97). LOA (LOA-%) was ±32.3 watt (W) (±22%) for LE power; ±22.7 N·m (±24%) for KE strength; ±0.2 m/s (±10%) for 40-m walk test; ±2.4 repetitions (±14%) for 30-second chair-stand test; and ±2 second (±20%) for stair climb test. A potential participant learning effect was found for all 3 performance-based tests, indicated by the significantly better scores at retest.The very high reliability found for the performance-based tests supports findings from previous studies and confirms discriminate reliability of these tests on a group level. Also, very high reliability estimates were demonstrated for both muscle function tests. This study also provided estimates of agreement for both performance-based and muscle function tests, which are important to consider when using these tests on an individual level in clinical practice.When using these tests to monitor changes over time in the clinic, depending on the test, improvements of less than 10% to 24% could be a result of measurement error alone and therefore may not be considered an actual improvement after treatment.
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19.
  • Irmola, Tero, et al. (författare)
  • Association between fixation type and revision risk in total knee arthroplasty patients aged 65 years and older : a cohort study of 265,877 patients from the Nordic Arthroplasty Register Association 2000–2016
  • 2021
  • Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 92:1, s. 91-96
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose — The population of the Nordic countries is aging and the number of elderly patients undergoing total knee arthroplasty (TKA) is also expected to increase. Reliable fixation methods are essential to avoid revisions. We compared the survival of different TKA fixation concepts with cemented fixation as the gold standard. Patients and methods — We used data from the Nordic Arthroplasty Register Association (NARA) database of 265,877 unconstrained TKAs performed for patients aged ≥ 65 years with primary knee osteoarthritis between 2000 and 2016. Kaplan–Meier (KM) survival analysis with 95% confidence intervals (CI) and the Cox multiple-regression model were used to compare the revision risk of the fixation methods. Results — Cemented fixation was used in 243,166 cases, uncemented in 8,000, hybrid (uncemented femur with cemented tibia) in 14,248, and inverse hybrid (cemented femur with uncemented tibia) fixation in 463 cases. The 10-year KM survivorship (95% CI) of cemented TKAs was 96% (96 − 97), uncemented 94% (94 − 95), hybrid 96% (96 − 96), and inverse hybrid 96% (94 − 99), respectively. Uncemented TKA was associated with increased risk of revision compared with the cemented TKA; the adjusted hazard ratio was 1.3 (95% CI 1.1 − 1.4). Interpretation — Cemented, hybrid, and inverse hybrid TKAs showed 10-year survival rates exceeding 95%. Uncemented fixation was associated with an increased risk of revision in comparison with cemented fixation. As both hybrid and inverse hybrid fixation were used in only a limited number of TKAs, indicating possibility of selection bias in their favor, cemented TKA still remains the gold standard, as it works reliably in the hands of many.
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20.
  • Irmola, Tero, et al. (författare)
  • Impact of the Nordic Arthroplasty Register Association (NARA) collaboration on demographics, methods and revision rates in knee arthroplasty : a register-based study from NARA 2000–2017
  • 2022
  • Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 93, s. 866-873
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose — We have previously observed differences in treatment and outcome of knee arthroplasties in the Nordic countries. To evaluate the impact of Nordic collaboration in the last 15 years we aimed to compare patient demographics, methods, and revision rates in primary knee arthroplasties among the 4 Nordic countries. Patients and methods — We included 535,051 primary knee arthroplasties reported 2000–2017 from the Nordic Arthroplasty Register Association (NARA) database. Kaplan–Meier analysis (KM) and restricted mean survival time (RMST) analysis were used to evaluate the cumulative revision rate (CRR) and RMST estimates with 95% confidence intervals (CI) and to compare countries in relation to risk of revision for any reason. Results — After 2010, the increase in incidence of knee arthroplasty plateaued in Sweden and Denmark but contin-ued to increase in Finland and Norway. In 2017 the incidence was highest in Finland with 226 per 105 person-years, while it was less than 150 per 105 in the 3 other Nordic coun-tries. In total knee arthroplasties performed for osteoarthri-tis (OA), overall CRR at 15 years for revision due to any reason was higher in Denmark (CRR 9.6%, 95% CI 9.2−10), Norway (CRR 9.1%, CI 8.7−9.5), and Finland (CRR 7.0%, CI 6.8−7.3) compared with Sweden (CRR 6.6%, CI 6.4−6.8). There were differences among the countries in use of implant brand and type, fixation, patellar component, and use of unicompartmental knee arthroplasty. Interpretation — We evinced a slowing growth of incidence of knee arthroplasties in the Nordic countries after 2010 with Finland having the highest incidence. We also noted substantial differences among the 4 Nordic countries, with Sweden having a lower risk of revision than the other countries. No impact of NARA could be demonstrated and CRR did not improve over time.
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21.
  • Jansen, Willemijn J, et al. (författare)
  • Association of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia.
  • 2018
  • Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 84-95
  • Tidskriftsartikel (refereegranskat)abstract
    • Cerebral amyloid-β aggregation is an early event in Alzheimer disease (AD). Understanding the association between amyloid aggregation and cognitive manifestation in persons without dementia is important for a better understanding of the course of AD and for the design of prevention trials.To investigate whether amyloid-β aggregation is associated with cognitive functioning in persons without dementia.This cross-sectional study included 2908 participants with normal cognition and 4133 with mild cognitive impairment (MCI) from 53 studies in the multicenter Amyloid Biomarker Study. Normal cognition was defined as having no cognitive concerns for which medical help was sought and scores within the normal range on cognitive tests. Mild cognitive impairment was diagnosed according to published criteria. Study inclusion began in 2013 and is ongoing. Data analysis was performed in January 2017.Global cognitive performance as assessed by the Mini-Mental State Examination (MMSE) and episodic memory performance as assessed by a verbal word learning test. Amyloid aggregation was measured with positron emission tomography or cerebrospinal fluid biomarkers and dichotomized as negative (normal) or positive (abnormal) according to study-specific cutoffs. Generalized estimating equations were used to examine the association between amyloid aggregation and low cognitive scores (MMSE score ≤27 or memory z score≤-1.28) and to assess whether this association was moderated by age, sex, educational level, or apolipoprotein E genotype.Among 2908 persons with normal cognition (mean [SD] age, 67.4 [12.8] years), amyloid positivity was associated with low memory scores after age 70 years (mean difference in amyloid positive vs negative, 4% [95% CI, 0%-7%] at 72 years and 21% [95% CI, 10%-33%] at 90 years) but was not associated with low MMSE scores (mean difference, 3% [95% CI, -1% to 6%], P=.16). Among 4133 patients with MCI (mean [SD] age, 70.2 [8.5] years), amyloid positivity was associated with low memory (mean difference, 16% [95% CI, 12%-20%], P<.001) and low MMSE (mean difference, 14% [95% CI, 12%-17%], P<.001) scores, and this association decreased with age. Low cognitive scores had limited utility for screening of amyloid positivity in persons with normal cognition and those with MCI. In persons with normal cognition, the age-related increase in low memory score paralleled the age-related increase in amyloid positivity with an intervening period of 10 to 15 years.Although low memory scores are an early marker of amyloid positivity, their value as a screening measure for early AD among persons without dementia is limited.
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22.
  • Jansen, Willemijn J, et al. (författare)
  • Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
  • 2022
  • Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
  • Tidskriftsartikel (refereegranskat)abstract
    • One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Alzheimer disease biomarkers detected on PET or in CSF.Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Among the 19097 participants (mean [SD] age, 69.1 [9.8] years; 10148 women [53.1%]) included, 10139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P=.04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P=.004), subjective cognitive decline (9%; 95% CI, 3%-15%; P=.005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P=.004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P=.18).This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
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23.
  • Jansen, Willemijn J, et al. (författare)
  • Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis.
  • 2015
  • Ingår i: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 313:19, s. 1924-38
  • Tidskriftsartikel (refereegranskat)abstract
    • Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies.
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24.
  • Jensen, Karen Schow, et al. (författare)
  • Temporal changes in incidence of relapse and outcome after relapse of childhood acute lymphoblastic leukemia over three decades : a Nordic population-based cohort study
  • 2022
  • Ingår i: Leukemia. - : Springer Nature. - 0887-6924 .- 1476-5551. ; 36, s. 1274-1282
  • Tidskriftsartikel (refereegranskat)abstract
    • Relapse remains the main obstacle to curing childhood acute lymphoblastic leukemia (ALL). The aims of this study were to compare incidence of relapse, prognostic factors, and survival after relapse between three consecutive Nordic Society of Pediatric Hematology and Oncology trials. Relapse occurred as a primary event in 638 of 4 458 children (1.0–14.9 years) diagnosed with Ph-negative ALL between 1992 and 2018. The 5-year cumulative incidence of relapse was 17.3% (95% CI 15.4–19.2%) and 16.5% (95% CI 14.3–18.8%) for patients in the ALL1992 and ALL2000 trials, respectively, but decreased to 8.4% (95% CI 7.0–10.1%) for patients in the ALL2008 trial. No changes in duration of first complete remission and site of relapse were observed over time; however, high hyperdiploidy, and t(12;21) decreased in the ALL2008 trial. The 4-year overall survival after relapse was 56.6% (95% CI 52.5–60.5%) and no statistically significant temporal improvements were observed. Age ≥10 years, T-cell immunophenotype, bone-marrow involvement, early and very early relapse, hypodiploidy, and Down syndrome all independently predicted worse outcome after relapse. Improvements in the primary treatment of childhood ALL has resulted in fewer relapses. However, failure to improve outcome of remaining relapses suggests a selection of harder-to-cure relapses and calls for new therapeutic strategies.
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25.
  • Jägerström, Sara, et al. (författare)
  • Lipid droplets interact with mitochondria using SNAP23.
  • 2009
  • Ingår i: Cell biology international. - : Wiley. - 1095-8355 .- 1065-6995. ; 33:9, s. 934-40
  • Tidskriftsartikel (refereegranskat)abstract
    • Triglyceride-containing lipid droplets (LD) are dynamic organelles stored on demand in all cells. These droplets grow through a fusion process mediated by SNARE proteins, including SNAP23. The droplets have also been shown to be highly motile and interact with other cell organelles, including peroxisomes and the endoplasmic reticulum. We have used electron and confocal microscopy to demonstrate that LD form complexes with mitochondria in NIH 3T3 fibroblasts. Using an in vitro system of purified LD and mitochondria, we also show the formation of the LD-mitochondria complex, in which cytosolic factors are involved. Moreover, the presence of LD markers in mitochondria isolated by subcellular fractionations is demonstrated. Finally, ablation of SNAP23 using siRNA reduced complex formation and beta oxidation, which suggests that the LD-mitochondria complex is functional in the cell.
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26.
  • Jönsson, Peter, et al. (författare)
  • High dose methotrexate treatment in children with acute lymphoblastic leukaemia may be optimised by a weight-based dose calculation.
  • 2011
  • Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5017 .- 1545-5009. ; 57, s. 41-46
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The inter-individual variation in exposure to methotrexate is considerable after intravenous high dose methotrexate (HDMTX) administration and both under- and over exposures may have dire consequences. Thus, optimal dose individualisation is of paramount importance. PROCEDURE: We studied how pharmacokinetic parameters were related to outcome in 340 patients with acute lymphoblastic leukaemia (ALL). A population pharmacokinetic model was developed with data from 1284 HDMTX courses in 304 children evaluating age, height, weight, body surface area (BSA), sex, serum creatinine and serum alanine aminotransferase as potential covariates. RESULT: Body weight improved the population pharmacokinetic model significantly more than any of the other patient characteristics, indicating that body weight may be the better way of dose normalisation. In a logistic regression analysis, higher values of clearance as well as volume of distribution were related to increased relapse risk in the standard (SR) and intermediate risk (IR) groups as well as in the entire cohort. A higher weight was strongly associated with worse outcome in the SR and IR groups, (P = 0.0186 and 0.0121, respectively). CONCLUSIONS: We conclude that dose normalisation of methotrexate according to body weigh may give more predictable pharmacokinetics of methotrexate and may also improve the outcome for children with ALL. Pediatr Blood Cancer © 2011 Wiley-Liss, Inc.
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27.
  • Knauss, Alessia, 1983, et al. (författare)
  • Paving the roadway for safety of automated vehicles : An empirical study on testing challenges
  • 2017
  • Ingår i: IEEE Intelligent Vehicles Symposium, Proceedings. - New York : IEEE. - 9781509048045 ; , s. 1873-1880
  • Konferensbidrag (refereegranskat)abstract
    • The technology in the area of automated vehicles is gaining speed and promises many advantages. However, with the recent introduction of conditionally automated driving, we have also seen accidents. Test protocols for both, conditionally automated (e.g., on highways) and automated vehicles do not exist yet and leave researchers and practitioners with different challenges. For instance, current test procedures do not suffice for fully automated vehicles, which are supposed to be completely in charge for the driving task and have no driver as a back up. This paper presents current challenges of testing the functionality and safety of automated vehicles derived from conducting focus groups and interviews with 26 participants from five countries having a background related to testing automotive safety-related topics. We provide an overview of the state-of-practice of testing active safety features as well as challenges that needs to be addressed in the future to ensure safety for automated vehicles. The major challenges identified through the interviews and focus groups, enriched by literature on this topic are related to 1) virtual testing and simulation, 2) safety, reliability, and quality, 3) sensors and sensor models, 4)required scenario complexity and amount of test cases, and 5)handover of responsibility between the driver and the vehicle. © 2017 IEEE.
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28.
  • Knauss, Alessia, 1983, et al. (författare)
  • Proving Ground Support for Automation of Testing of Active Safety Systems and Automated Vehicles
  • 2017
  • Ingår i: 4th International Symposium on Future Active Safety Technology towards Zero-Traffic-Accidents (FAST-zero).
  • Konferensbidrag (refereegranskat)abstract
    • Research in the area of autonomous vehicles is advancing in a fast pace. Companies focus on delivering vehicles with automated driving functions, where the driver still has to monitor the vehicle. While the advancements on algorithm development are enormous, the area of testing and verifying such kind of vehicles is still in a very early stage. Testing of active safety systems is well established already and a first step in this direction. However, the methods and techniques currently used for testing of active safety systems at the proving grounds will not scale to testing of automated vehicles. This will result in high costs and efforts – if done manually as it mianly is now. Hence, automation of testing at proving grounds is a necessary step in the direction of testing autonomous vehicles. In this paper, we present a study on the proving ground support needed for test automation of active safety and autonomous vehicle testing. We show that the focus should be on data and equipment related aspects to move in the direction of automated testing of autonomous vehicles.
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29.
  • Knauss, Alessia, 1983, et al. (författare)
  • Software-related challenges of testing automated vehicles
  • 2017
  • Ingår i: Proceedings - 2017 IEEE/ACM 39th International Conference on Software Engineering Companion, ICSE-C 2017. - : ACM. - 9781538615898 ; , s. 328-330
  • Konferensbidrag (refereegranskat)abstract
    • Automated vehicles are not supposed to fail at any time or in any situations during driving. Thus, vehicle manufactures and proving ground operators are challenged to complement existing test procedures with means to systematically evaluate automated driving. In this paper, we explore software related challenges from testing the safety of automated vehicles. We report on findings from conducting focus groups and interviews including 26 participants (e.g., vehicle manufacturers, suppliers, and researchers) from five countries.
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30.
  • Langreth, D. C., et al. (författare)
  • A density functional for sparse matter
  • 2009
  • Ingår i: Journal of Physics Condensed Matter. - : IOP Publishing. - 0953-8984 .- 1361-648X. ; 21:8, s. 084203-
  • Tidskriftsartikel (refereegranskat)abstract
    • Sparse matter is abundant and has both strong local bonds and weak nonbonding forces, in particular nonlocal van der Waals (vdW) forces between atoms separated by empty space. It encompasses a broad spectrum of systems, like soft matter, adsorption systems and biostructures. Density-functional theory (DFT), long since proven successful for dense matter, seems now to have come to a point, where useful extensions to sparse matter are available. In particular, a functional form, vdW-DF (Dion et al 2004 Phys. Rev. Lett. 92 246401; Thonhauser et al 2007 Phys. Rev. B 76 125112), has been proposed for the nonlocal correlations between electrons and applied to various relevant molecules and materials, including to those layered systems like graphite, boron nitride and molybdenum sulfide, to dimers of benzene, polycyclic aromatic hydrocarbons (PAHs), doped benzene, cytosine and DNA base pairs, to nonbonding forces in molecules, to adsorbed molecules, like benzene, naphthalene, phenol and adenine on graphite, alumina and metals, to polymer and carbon nanotube (CNT) crystals, and hydrogen storage in graphite and metal–organic frameworks (MOFs), and to the structure of DNA and of DNA with intercalators. Comparison with results from wavefunction calculations for the smaller systems and with experimental data for the extended ones show the vdW-DF path to be promising. This could have great ramifications.
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31.
  • Langreth, D. C., et al. (författare)
  • Van der Waals Density Functional Theory with Applications
  • 2005
  • Ingår i: International Journal of Quantum Chemistry. - : Wiley. - 0020-7608 .- 1097-461X. ; 101:5, s. 599-610
  • Tidskriftsartikel (refereegranskat)abstract
    • The details of a density functional that includes van der Waals (vdW) interactions are presented. In particular we give some key steps of the transition from a form for fully planar systems to a procedure for realistic layered compounds that have planar symmetry only on large-distance scales, and which have strong covalent bonds within the layers. It is shown that the random-phase approximation of that original functional can be replaced by an approximation that is exact at large separation between vdW interacting fragments and seamless as the fragments merge. An approximation to the latter which renders the functional easily applicable and which preserves useful accuracy in both limits and in between is given. We report additional data from applications to forms of graphite, boron nitride, and molybdenum sulfide not reported in our previous communication.(C) 2004 Wiley Periodicals, Inc.
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32.
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33.
  • Maarbjerg, Sabine F., et al. (författare)
  • Continuous infusion of piperacillin‐tazobactam significantly improves target attainment in children with cancer and fever
  • 2021
  • Ingår i: Cancer Reports. - : John Wiley & Sons. - 2573-8348. ; 5:10
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundChildren with febrile neutropenia commonly exhibit alterations of pharmacokinetic (PK) parameters, leading to decreased β-lactam concentrations.AimsThis study evaluated piperacillin PK and probability of target attainment (PTA) with continuous infusion of piperacillin-tazobactam, in order to optimize the dosing regimen.MethodsThis prospective PK study included children with cancer, aged 1–17 years, who were treated with piperacillin-tazobactam for suspected or verified infection. A piperacillin-tazobactam loading dose (100 mg/kg) was administered followed by continuous infusion (300 mg/kg/day). The unbound fraction of piperacillin was quantified by high-performance liquid chromatography and PK were described using population PK modeling. PK data was used to update and extend a previous PK model built on data following intermittent administration. Monte Carlo simulations were performed to assess PTA for targets of 100% time above the minimum inhibitory concentration (100% fT > MIC) and 50% fT > 4xMIC.ResultsWe included 68 fever episodes among 38 children with a median (IQR) age of 6.5 years and body weight of 27.4 kg (15.1–54.0). A three-compartment model adequately described the concentration-time data. Median (95% confidence interval) estimates for clearance and piperacillin concentration at steady state were 14.2 L/h/70 kg (13.0; 15.3) and 47.6 mg/L (17.2; 129.5), respectively. Body weight or lean body weight was significantly associated with the PK parameters, and body weight was integrated in the final PK model. Based on piperacillin exposure, continuous infusion was the only dosing regimen to achieve optimal PTA for the P. aeruginosa breakpoint (16 mg/L) with the target of 100% fT > MIC, and a daily dose of 300 mg/kg reached optimal PTA. The strict target of 50% fT > 4xMIC (64 mg/L) was not feasibly attained by any dosing regimen at recommended doses.ConclusionUnlike conventional piperacillin intermittent administration and extended infusion regimens, continuous infusion allows the target of 100% fT > MIC to be reached for children with febrile neutropenia.
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34.
  • Mackey, Abigail L., et al. (författare)
  • The influence of anti-inflammatory medication on exercise-induced myogenic precursor cell responses in humans
  • 2007
  • Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 103:2, s. 425-431
  • Tidskriftsartikel (refereegranskat)abstract
    • The consumption of nonsteroidal anti-inflammatory drugs (NSAIDs) is widespread among athletes when faced with muscle soreness or injury, but the effects of NSAIDs on satellite cell activity in humans are unknown. To investigate this, 14 healthy male endurance athletes (mean peak oxygen consumption 62 ml x kg(-1) x min(-1)) volunteered for the study, which involved running 36 km. They were divided into two groups and received either 100 mg indomethacin per day or placebo. Muscle biopsies collected before the run and on days 1, 3, and 8 afterward were analyzed for satellite cells by immunohistochemistry with the aid of neural cell adhesion molecule (NCAM) and fetal antigen-1 (FA1) antibodies. Muscle biopsies were also collected from untrained individuals for comparison. Compared with preexercise levels, a 27% increase in the number of NCAM+ cells was observed on day 8 postexercise in the placebo group (P < 0.05), while levels remained similar at all time points in the NSAID group. No change was seen in the proportion of FA1+ cells, although lower levels were found in the muscle of endurance-trained athletes compared with untrained individuals (P < 0.05). These results suggest that ingestion of anti-inflammatory drugs attenuates the exercise-induced increase in satellite cell number, supporting the role of the cyclooxygenase pathway in satellite cell activity.
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35.
  • Mattsson, Niklas, 1979, et al. (författare)
  • Age and diagnostic performance of Alzheimer disease CSF biomarkers.
  • 2012
  • Ingår i: Neurology. - : American Academy of Neurology (AAN). - 1526-632X .- 0028-3878. ; 78:7, s. 468-76
  • Tidskriftsartikel (refereegranskat)abstract
    • Core CSF changes in Alzheimer disease (AD) are decreased amyloid β(1-42), increased total tau, and increased phospho-tau, probably indicating amyloid plaque accumulation, axonal degeneration, and tangle pathology, respectively. These biomarkers identify AD already at the predementia stage, but their diagnostic performance might be affected by age-dependent increase of AD-type brain pathology in cognitively unaffected elderly.
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36.
  • Mattsson, Niklas, 1979, et al. (författare)
  • CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment.
  • 2009
  • Ingår i: JAMA : the journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 302:4, s. 385-93
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: Small single-center studies have shown that cerebrospinal fluid (CSF) biomarkers may be useful to identify incipient Alzheimer disease (AD) in patients with mild cognitive impairment (MCI), but large-scale multicenter studies have not been conducted. OBJECTIVE: To determine the diagnostic accuracy of CSF beta-amyloid(1-42) (Abeta42), total tau protein (T-tau), and tau phosphorylated at position threonine 181 (P-tau) for predicting incipient AD in patients with MCI. DESIGN, SETTING, AND PARTICIPANTS: The study had 2 parts: a cross-sectional study involving patients with AD and controls to identify cut points, followed by a prospective cohort study involving patients with MCI, conducted 1990-2007. A total of 750 individuals with MCI, 529 with AD, and 304 controls were recruited by 12 centers in Europe and the United States. Individuals with MCI were followed up for at least 2 years or until symptoms had progressed to clinical dementia. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative likelihood ratios (LRs) of CSF Abeta42, T-tau, and P-tau for identifying incipient AD. RESULTS: During follow-up, 271 participants with MCI were diagnosed with AD and 59 with other dementias. The Abeta42 assay in particular had considerable intersite variability. Patients who developed AD had lower median Abeta42 (356; range, 96-1075 ng/L) and higher P-tau (81; range, 15-183 ng/L) and T-tau (582; range, 83-2174 ng/L) levels than MCI patients who did not develop AD during follow-up (579; range, 121-1420 ng/L for Abeta42; 53; range, 15-163 ng/L for P-tau; and 294; range, 31-2483 ng/L for T-tau, P < .001). The area under the receiver operating characteristic curve was 0.78 (95% confidence interval [CI], 0.75-0.82) for Abeta42, 0.76 (95% CI, 0.72-0.80) for P-tau, and 0.79 (95% CI, 0.76-0.83) for T-tau. Cut-offs with sensitivity set to 85% were defined in the AD and control groups and tested in the MCI group, where the combination of Abeta42/P-tau ratio and T-tau identified incipient AD with a sensitivity of 83% (95% CI, 78%-88%), specificity 72% (95% CI, 68%-76%), positive LR, 3.0 (95% CI, 2.5-3.4), and negative LR, 0.24 (95% CI, 0.21-0.28). The positive predictive value was 62% and the negative predictive value was 88%. CONCLUSIONS: This multicenter study found that CSF Abeta42, T-tau, and P-tau identify incipient AD with good accuracy, but less accurately than reported from single-center studies. Intersite assay variability highlights a need for standardization of analytical techniques and clinical procedures.
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37.
  • Mattsson, Niklas, et al. (författare)
  • Prevalence of the apolipoprotein E ε4 allele in amyloid β positive subjects across the spectrum of Alzheimer's disease
  • 2018
  • Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 14:7, s. 913-924
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Apolipoprotein E (APOE) ε4 is the major genetic risk factor for Alzheimer's disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid β (Aβ) pathology. Methods: We included 3451 Aβ+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE ε4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE ε4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in Aβ+ cognitively normal and Aβ+ mild cognitive impairment (P <.05) but not in Aβ+ AD dementia (P =.66). The prevalence was highest in Northern Europe but did not vary by sex or education. Discussion: The APOE ε4 prevalence in AD was higher than that in previous studies, which did not require presence of Aβ pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location.
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38.
  • Mattsson, Niklas, 1979, et al. (författare)
  • The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers.
  • 2011
  • Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 7:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer's disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer's Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program.
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39.
  • Nielsen, Joachim, et al. (författare)
  • Increased subsarcolemmal lipids in type 2 diabetes : effect of training on localization of lipids, mitochondria, and glycogen in sedentary human skeletal muscle.
  • 2010
  • Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 298:3, s. E706-13
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of the study was to investigate the effect of aerobic training and type 2 diabetes on intramyocellular localization of lipids, mitochondria, and glycogen. Obese type 2 diabetic patients (n = 12) and matched obese controls (n = 12) participated in aerobic cycling training for 10 wk. Endurance-trained athletes (n = 15) were included for comparison. Insulin action was determined by euglycemic-hyperinsulinemic clamp. Intramyocellular contents of lipids, mitochondria, and glycogen at different subcellular compartments were assessed by transmission electron microscopy in biopsies obtained from vastus lateralis muscle. Type 2 diabetic patients were more insulin resistant than obese controls and had threefold higher volume of subsarcolemmal (SS) lipids compared with obese controls and endurance-trained subjects. No difference was found in intermyofibrillar lipids. Importantly, following aerobic training, this excess SS lipid volume was lowered by approximately 50%, approaching the levels observed in the nondiabetic subjects. A strong inverse association between insulin sensitivity and SS lipid volume was found (r(2)=0.62, P = 0.002). The volume density and localization of mitochondria and glycogen were the same in type 2 diabetic patients and control subjects, and showed in parallel with improved insulin sensitivity a similar increase in response to training, however, with a more pronounced increase in SS mitochondria and SS glycogen than in other localizations. In conclusion, this study, estimating intramyocellular localization of lipids, mitochondria, and glycogen, indicates that type 2 diabetic patients may be exposed to increased levels of SS lipids. Thus consideration of cell compartmentation may advance the understanding of the role of lipids in muscle function and type 2 diabetes.
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40.
  • Nielsen, Joachim, et al. (författare)
  • Skeletal muscle glycogen content and particle size of distinct subcellular localizations in the recovery period after a high-level soccer match
  • 2012
  • Ingår i: European Journal of Applied Physiology. - : Springer Science and Business Media LLC. - 1439-6319 .- 1439-6327. ; 112:10, s. 3559-3567
  • Tidskriftsartikel (refereegranskat)abstract
    • Whole muscle glycogen levels remain low for a prolonged period following a soccer match. The present study was conducted to investigate how this relates to glycogen content and particle size in distinct subcellular localizations. Seven high-level male soccer players had a vastus lateralis muscle biopsy collected immediately after and 24, 48, 72 and 120 h after a competitive soccer match. Transmission electron microscopy was used to estimate the subcellular distribution of glycogen and individual particle size. During the first day of recovery, glycogen content increased by ~60% in all subcellular localizations, but during the subsequent second day of recovery glycogen content located within the myofibrils (Intramyofibrillar glycogen, a minor deposition constituting 10–15% of total glycogen) did not increase further compared with an increase in subsarcolemmal glycogen (−7 vs. +25%, respectively, P = 0.047). Conversely, from the second to the fifth day of recovery, glycogen content increased (53%) within the myofibrils compared to no change in subsarcolemmal or intermyofibrillar glycogen (P < 0.005). Independent of location, increment in particle size preceded increment in number of particles. Intriguingly, average particle size decreased; however, in the period from 3 to 5 days after the match. These findings suggest that glycogen storage in skeletal muscle is influenced by subcellular localization-specific mechanisms, which account for an increase in number of glycogen particles located within the myofibrils in the period from 2 to 5 days after the soccer match.
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41.
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42.
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43.
  • NiemeläInen, Mika J., et al. (författare)
  • Different incidences of knee arthroplasty in the Nordic countries : A population-based study from the Nordic Arthroplasty Register Association
  • 2017
  • Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 88:2, s. 173-178
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose — The annual number of total knee arthroplasties (TKAs) has increased worldwide in recent years. To make projections regarding future needs for primaries and revisions, additional knowledge is important. We analyzed and compared the incidences among 4 Nordic countries Patients and methods — Using Nordic Arthroplasty Register Association (NARA) data from 4 countries, we analyzed differences between age and sex groups. We included patients over 30 years of age who were operated with TKA or unicompartmental knee arthroplasty (UKA) during the period 1997–2012. The negative binomial regression model was used to analyze changes in general trends and in sex and age groups. Results — The average annual increase in the incidence of TKA was statistically significant in all countries. The incidence of TKA was higher in women than in men in all 4 countries. It was highest in Finland in patients aged 65 years or more. At the end of the study period in 2012, Finland’s total incidence was double that of Norway, 1.3 times that of Sweden and 1.4 times that of Denmark. The incidence was lowest in the youngest age groups (< 65 years) in all 4 countries. The proportional increase in incidence was highest in patients who were younger than 65 years. Interpretation — The incidence of knee arthroplasty steadily increased in the 4 countries over the study period. The differences between the countries were considerable, with the highest incidence in Finland. Patients aged 65 years or more contributed to most of the total incidence of knee arthroplasty.
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44.
  • Niemeläinen, Mika J., et al. (författare)
  • The effect of fixation type on the survivorship of contemporary total knee arthroplasty in patients younger than 65 years of age : a register-based study of 115,177 knees in the Nordic Arthroplasty Register Association (NARA) 2000–2016
  • 2020
  • Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 91:2, s. 184-190
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose — Cemented fixation is regarded as the gold standard in total knee arthroplasty (TKA). Among working-age patients, there has been controversy regarding the optimal fixation method in TKA. To address this issue, we conducted a register-based study to assess the survivorship of cemented, uncemented, hybrid, and inverse hybrid TKAs in patients aged < 65 years. Patients and methods — We used the Nordic Arthroplasty Register Association data of 115,177 unconstrained TKAs performed for patients aged < 65 years with primary knee osteoarthritis over 2000–2016. Kaplan–Meier (KM) survival analysis with 95% confidence intervals (CI) and Cox multiple-regression model with adjustment for age, sex, and nation were used to compare fixation methods in relation to revision for any reason. Results — The 10-year KM survivorship of cemented TKAs was 93.6% (95% CI 93.4–93.8), uncemented 91.2% (CI 90.1–92.2), hybrid 93.0% (Cl 92.2–93.8), and inverse hybrid 96.0% (CI 94.1–98.1). In the Cox model, hybrid TKA showed decreased risk of revision after 6 years’ follow-up compared with the reference group (cemented) (hazard ratio [HR] 0.5 [CI 0.4–0.8]), while uncemented TKAs showed increased risk of revision both < 1 year (HR 1.4 [1.1–1.7]) and > 6 years’ (HR 1.3 [1.0–1.7]) follow-up compared to the reference. Interpretation — Both cemented and hybrid TKAs had 10-year survival rates exceeding 92–>93% in patients aged < 65 years. Cemented TKA, however, was used in the vast majority (89%) of the operations in the current study. As it performs reliably in the hands of many, it still deserves the status of gold standard for TKA in working-age patients.
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45.
  • Norén Nyström, Ulrika, 1965- (författare)
  • Vascular density and bone marrow fibrosis in childhood acute lymphoblastic leukemia
  • 2008
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background: In childhood acute lymphoblastic leukemia (ALL), the cure rate has now reached 80% in the western world. Even so, 15¬–20% will die from the disease or treatment-related causes, among them children who did not present any known unfavorable features at diagnosis. Treatment of childhood ALL is risk-adapted, meaning that certain factors that are related to the child or the leukemic blasts stratifies to more or less intensive treatment. In this thesis, characteristics of the bone marrow (BM) stroma, reflecting the interaction between the leukemic cells and their microenvironment, were evaluated. The aims were to investigate these factors in relation to other known data in order to further understand the biology of leukemia, and to suggest additional risk factors that would further improve decision making for the treatment of individual children diagnosed with ALL. Methods: We retrospectively investigated microvessel density (MVD), blast-congested vessel fraction (BCVF), and degree of fibrosis – reticulin fiber density (RFD) – in sections from diagnostic BM biopsies from children diagnosed in Umeå, Uppsala, and Stockholm. RFD was also studied in BM sections from treatment day 29. Results: RFD had prognostic impact in patients with high-hyperdiploid (HeH) leukemia. Moreover, rapid reduction of RFD during induction treatment was associated with a favorable prognosis compared to slow reduction, in B-cell precursor (BCP) ALL patients. There was also a correlation between RFD at diagnosis and minimal residual disease (MRD) measured by flow cytometry on treatment day 29 in BCP patients. BCP patients with high RFD and high MVD had an unfavorable outcome compared to all other BCP patients. In addition, MVD and RFD were both associated with immunophenotype, and MVD with cytogenetic aberrations. There was a correlation between MVD and WBC count in BCP high-risk patients. There was also a strong correlation between BCVF and WBC count in all BCP patients, but not between BCVF and MVD or RFD. There was a negative correlation between MVD and in vitro cellular resistance to several drugs in BCP patients. A drug-resistance score combining the drugs most strongly correlated to MVD – cytarabine, doxorubicin, and dexametasone (ADD score) – identified the prognostic potential of ADD score in HeH patients with no unfavorable features. Conclusions: Taken together, these studies indicate that stroma factors in leukemia are related to both phenotypic and genotypic features of acute leukemia. Stroma factors also seem to influence the response to induction treatment, in vitro drug resistance, and outcome in certain subgroups of childhood ALL patients. The results emphasize the importance of BM stroma in leukemia and the need for greater use of BM biopsy at diagnosis.
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46.
  • Palle, Josefine, 1964- (författare)
  • Optimizing Chemotherapy in Childhood Acute Myeloid Leukemia
  • 2008
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Despite major advances in our understanding of the biology of childhood acute myeloid leukemia (AML) and the development of new cytotoxic drugs, the prognosis of long-term survival is still only 60-65 %.In the present research, we studied the pharmacokinetics of drugs used in the induction therapy of childhood AML and performed in vitro drug sensitivity testing of leukemic cells from children with AML.The aims of the studies were to correlate the results of the analysis to biological and clinical parameters and to identify subgroups of AML with specific drug sensitivity profiles in order to better understand why treatment fails in some patients and how therapy may be improved.Blood samples were analysed to study the pharmacokinetics of doxorubicin (n=41), etoposide (n=45) and 6-thioguanine (n=50). Doxorubicin plasma concentration and total body clearance were correlated to the effect of induction therapy, and doxorubicin plasma concentration was an independent factor for complete remission, both in univariate and multivariate analysis including sex, age, and white blood cell count at diagnosis. For etoposide and 6-thioguanine no correlation was found between pharmacokinetics and clinical effect. Children with Down syndrome (DS) tended to reach higher blood concentrations of etoposide and thioguanine nucleotides, indicating that dose reduction may be reasonable to reach the same drug exposure as in children without DS.Leukemic cells from 201 children with newly diagnosed AML, 15 of whom had DS, were successfully analysed for in vitro drug sensitivity by the fluorometric microculture cytotoxicity assay (FMCA). We found that samples from children with DS were highly sensitive to most drugs used in AML treatment. In non-DS children, the t(9;11) samples were significantly more sensitive to cytarabine (p=0.03) and doxorubicin (p=0.035) than other samples. The findings might explain the very favorable outcome reported in children with DS and t(9;11)-positive AML. A specific drug resistance profile was found for several other genetic subgroups as well. A detailed study of MLL-rearranged leukemia showed that cellular drug sensitivity is correlated both to partner genes and cell lineage, findings that support the strategy of contemporary protocols to include high-dose cytarabine in the treatment of patients with MLL-rearrangement, both in AML and acute lymphoblastic leukemia (ALL).Our results indicate that drug resistance and pharmacokinetic studies may yield important information regarding drug response in different sub-groups of childhood AML, helping us to optimize future chemotherapy in childhood AML.
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47.
  • Petäjä, Tuukka, et al. (författare)
  • Overview : Integrative and Comprehensive Understanding on Polar Environments (iCUPE) - concept and initial results
  • 2020
  • Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 20:14, s. 8551-8592
  • Tidskriftsartikel (refereegranskat)abstract
    • The role of polar regions is increasing in terms of megatrends such as globalization, new transport routes, demography, and the use of natural resources with consequent effects on regional and transported pollutant concentrations. We set up the ERA-PLANET Strand 4 project iCUPE - integrative and Comprehensive Understanding on Polar Environments to provide novel insights and observational data on global grand challenges with an Arctic focus. We utilize an integrated approach combining in situ observations, satellite remote sensing Earth observations (EOs), and multi-scale modeling to synthesize data from comprehensive long-term measurements, intensive campaigns, and satellites to deliver data products, metrics, and indicators to stakeholders concerning the environmental status, availability, and extraction of natural resources in the polar areas. The iCUPE work consists of thematic state-of-the-art research and the provision of novel data in atmospheric pollution, local sources and transboundary transport, the characterization of arctic surfaces and their changes, an assessment of the concentrations and impacts of heavy metals and persistent organic pollutants and their cycling, the quantification of emissions from natural resource extraction, and the validation and optimization of satellite Earth observation (EO) data streams. In this paper we introduce the iCUPE project and summarize initial results arising out of the integration of comprehensive in situ observations, satellite remote sensing, and multi-scale modeling in the Arctic context.
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48.
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49.
  • Schröder, Karin, 1966-, et al. (författare)
  • Effectiveness and Quality of Implementing a Best Practice Model of Care for Low Back Pain (BetterBack) Compared with Routine Care in Physiotherapy : A Hybrid Type 2 Trial
  • 2021
  • Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 10:6, s. 1230-
  • Tidskriftsartikel (refereegranskat)abstract
    • Low back pain (LBP) occurs in all ages and first-line treatment by physiotherapists is common. The main aim of the current study was to evaluate the effectiveness of implementing a best practice model of care for LBP (intervention group—BetterBackJ MoC) compared to routine physiotherapy care (control group) regarding longitudinal patient reported outcomes. The BetterBackJ MoC contains clinical guideline recommendations and support tools to facilitate clinician adherence to guidelines. A secondary exploratory aim was to compare patient outcomes based on the fidelity of fulfilling a clinical practice quality index regarding physiotherapist care. A stepped cluster randomized design nested patients with LBP in the three clusters which were allocated to control (n = 203) or intervention (n = 264). Patient reported measures were collected at baseline, 3, 6 and 12 months and analyzed with mixed model regression. The primary outcome was between-group changes from baseline to 3 months for pain intensity and disability. Implementation of the BetterBackJ MoC did not show any between-group differences in the primary outcomes compared with routine care. However, the intervention group showed significantly higher satisfaction at 3 months and clinically meaningful greater improvement in LBP illness perception at 3 months and quality of life at 3 and 6 months but not in patient enablement and global impression of change compared with the control group. Physiotherapists’ care that adhered to all clinical practice quality indices resulted in an improvement of most patient reported outcomes with a clinically meaningful greater improved LBP illness perception at 3 month and quality of life at 3 and 6 months, significantly greater improvement in LBP illness perception, pain and satisfaction at 3 and 6 months and significantly better enablement at all time points as well as better global improvement outcomes at 3 months compared with non-adherent care. This highlights the importance of clinical guideline based primary care for improving patient reported LBP outcomes.
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50.
  • Schröder, Karin, 1966-, et al. (författare)
  • Improved adherence to clinical guidelines for low back pain after implementation of the BetterBack model of care: A stepped cluster randomized controlled trial within a hybrid type 2 trial
  • 2023
  • Ingår i: Physiotherapy Theory and Practice. - : Taylor & Francis. - 0959-3985 .- 1532-5040. ; 39:7, s. 1376-1390
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND The BetterBack model of care (MoC) for low back pain (LBP) was recently developed in Swedish physiotherapy (PT) primary care.OBJECTIVE To evaluate if PTs’ adherence to LBP clinical practice guidelines (CPGs) improves after implementation of the BetterBack MoC (intervention).METHODS This was a stepped, single-blinded cluster randomized controlled trial. Patients nested in the three clusters were allocated to routine care (n = 222) or intervention (n = 278). The primary outcome was referral to specialist consultation. This was among five best practice recommendations divided into an assessment quality index (no referral to specialist consultation and no medical imaging) and a treatment quality index (use of educational interventions; use of exercise interventions; no use of non-evidence-based physiotherapy). For overall adherence, patients had to be treated with all five recommendations fulfilled. Logistic regression was used for between-group comparisons.RESULTS The proportion of patients receiving referral to specialist consultation during the PT treatment period was low in both groups with no between-group differences. However, patients in the intervention group showed significantly higher assessment quality index, treatment quality index and overall adherence compared to routine care. Adherence to the separate recommendations showed improved stratified number of visits, use of exercise was maintained high, patient educational intervention increased and use of non-evidence-based physiotherapy decreased. A reduction of medical imaging during the physiotherapy treatment period was also observed.CONCLUSIONS The adoption of CPGs could be substantially improved by introducing a MoC through PT training and supportive materials.
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