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| 2. |
- Almqvist, Helena, et al.
(författare)
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CETSA screening identifies known and novel thymidylate synthase inhibitors and slow intracellular activation of 5-fluorouracil
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Target engagement is a critical factor for therapeutic efficacy. Assessment of compound binding to native target proteins in live cells is therefore highly desirable in all stages of drug discovery. We report here the first compound library screen based on biophysical measurements of intracellular target binding, exemplified by human thymidylate synthase (TS). The screen selected accurately for all the tested known drugs acting on TS. We also identified TS inhibitors with novel chemistry and marketed drugs that were not previously known to target TS, including the DNA methyltransferase inhibitor decitabine. By following the cellular uptake and enzymatic conversion of known drugs we correlated the appearance of active metabolites over time with intracellular target engagement. These data distinguished a much slower activation of 5-fluorouracil when compared with nucleoside-based drugs. The approach establishes efficient means to associate drug uptake and activation with target binding during drug discovery.
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| 3. |
- Augustinsson, Sören, et al.
(författare)
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Karriärövergång från medarbetare till skolledare inom förskola/skola
- 2023
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Ingår i: Arbetsmarknad och Arbetsliv. ; , s. 25
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Vi är intresserade av vilka sammanhang, situationer och motiv som är centrala när individer genomför en karriärövergång från medarbetare till skolledare inom förskola/skola för första gången. En brytpunkt som äger rum inom ramen för individens handlingshorisont. Resultaten visar en sammanflätad komplex process där olika delar påverkar varandra och tillsammans skapar helheten. Teoretiskt har vi ett särskilt fokus på karriär utifrån Careership- och Planned Happenstanceteori. Vår studie är av både kvantitativ och kvalitativ karaktär men huvudfokus i artikeln utgår från två kvalitativa frågor. Studien genomfördes under 2016 - 2017 bland deltagare i rektorsprogrammet vid Linnéuniversitetet.
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| 4. |
- Axelsson, Kristian F, 1973, et al.
(författare)
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Analysis of Comorbidities, Clinical Outcomes, and Parathyroidectomy in Adults With Primary Hyperparathyroidism
- 2022
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Ingår i: Jama Network Open. - : American Medical Association (AMA). - 2574-3805. ; 5:6
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Patients with primary hyperparathyroidism (pHPT) appear to have an increased risk of fractures and other comorbidities, such as cardiovascular disease, although results from previous studies have been inconsistent. Evidence of the association of parathyroidectomy (PTX) with these outcomes is also limited because of the lack of large well-controlled trials. OBJECTIVE To investigate whether untreated pHPT was associated with an increased risk of incident fractures and cardiovascular events (CVEs) and whether PTX was associated with a reduced risk of these outcomes. DESIGN, SETTING, AND PARTICIPANTS This cohort study included all patients who were diagnosed with pHPT at hospitals in Sweden between July 1, 2006, and December 31, 2017. Each patient was matched with 10 control individuals from the general population by sex, birth year, and county of residence. The patients were followed up until December 31, 2017. Data analyses were performed from October 2021 to April 2022. MAIN OUTCOMES AND MEASURES The primary outcomes were fractures, CVEs, and death. Cumulative incidence of events was estimated using the 1-minus Kaplan-Meier estimator of corresponding survival function. Cox proportional hazards regression models were used to calculate hazard ratios (HRs). RESULTS A total of 16 374 patients with pHPT were identified (mean [SD] age, 67.5 [12.9] years; 12 806 women [78.2%]), with 163 740 control individuals. The follow-up time was 42 310 person-years for the pH PT group and 803 522 person-years for the control group. Compared with the control group, the pH PT group had a higher risk of any fracture (unadjusted HR, 1.39; 95% CI, 1.31-1.48), hip fracture (unadjusted HR, 1.51; 95% CI, 1.35-1.70), CVEs (unadjusted HR, 1.45; 95% CI, 1.34-1.57), and death (unadjusted HR, 1.72; 95% CI, 1.65-1.80). In a time-dependent Poisson regression model, PTX was associated with a reduced risk of any fracture (HR, 0.83; 95% CI, 0.75-0.93), hip fracture (HR, 0.78; 95% CI, 0.61-0.98), CVEs (HR, 0.84; 95% CI, 0.73-0.97), and death (HR, 0.59; 95% CI, 0.53-0.65). CONCLUSIONS AND RELEVANCE Results of this study suggest that pHPT is associated with increased risk of fractures, CVEs, and death, highlighting the importance of identifying patients with this condition to prevent serious unfavorable outcomes. The reduced risk of these outcomes associated with PTX suggests a clinical benefit of surgery.
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| 5. |
- Axelsson, Kristian F., et al.
(författare)
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Association Between Recurrent Fracture Risk and Implementation of Fracture Liaison Services in Four Swedish Hospitals: A Cohort Study
- 2020
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 35:7, s. 1216-1223
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Tidskriftsartikel (refereegranskat)abstract
- © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research Structured secondary preventions programs, called fracture liaison services (FLSs), increase the rate of evaluation with bone densitometry and use of osteoporosis medication after fracture. However, the evidence regarding the effect on the risk of recurrent fracture is insufficient. The aim of this study was to investigate if implementation of FLS was associated with reduced risk of recurrent fractures. In this retrospective cohort study, electronic health records during 2012 to 2017 were used to identify a total of 21,083 patients from four hospitals in Western Sweden, two with FLS (n = 15,449) and two without (n = 5634). All patients aged 50 years or older (mean age 73.9 [SD 12.4] years, 76% women) with a major osteoporotic index fracture (hip, clinical spine, humerus, radius, and pelvis) were included. The primary outcome was recurrent major osteoporotic fracture. All patients with an index fracture during the FLS period (n = 13,946) were compared with all patients in the period before FLS implementation (n = 7137) in an intention-to-treat analysis. Time periods corresponding to the FLS hospitals were used for the non-FLS hospitals. In the hospitals with FLSs, there were 1247 recurrent fractures during a median follow-up time of 2.2 years (range 0–6 years). In an unadjusted Cox model, the risk of recurrent fracture was 18% lower in the FLS period compared with the control period (hazard ratio = 0.82, 95% confidence interval [CI] 0.73–0.92, p = 0.001), corresponding to a 3-year number needed to screen of 61, and did not change after adjustment for clinical risk factors. In the hospitals without FLSs, no change in recurrent fracture rate was observed. Treatment decisions were made according to the Swedish treatment guidelines. In conclusion, implementation of FLS was associated with a reduced risk of recurrent fracture, indicating that FLSs should be included routinely at hospitals treating fracture patients. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.
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| 7. |
- Axelsson, Malin, et al.
(författare)
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Differences in diagnostic patterns of obstructive airway disease between areas and sex in Sweden and Finland : The Nordic EpiLung Study
- 2021
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Ingår i: Journal of Asthma. - : Taylor & Francis. - 0277-0903 .- 1532-4303. ; 58:9, s. 1196-1207
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the current prevalence of physician-diagnosed obstructive airway diseases by respiratory symptoms and by sex in Sweden and Finland. Method: In 2016, a postal questionnaire was answered by 34,072 randomly selected adults in four study areas: Västra Götaland and Norrbotten in Sweden, and Seinäjoki-Vaasa and Helsinki in Finland. Results: The prevalence of asthma symptoms was higher in Norrbotten (13.2%), Seinäjoki-Vaasa (14.8%) and Helsinki (14.4%) than in Västra Götaland (10.7%), and physician-diagnosed asthma was highest in Norrbotten (13.0%) and least in Västra Götaland (10.1%). Chronic productive cough was most common in the Finnish areas (7.7-8.2 % versus 6.3-6.7 %) while the prevalence of physician-diagnosed chronic bronchitis (CB) or chronic obstructive pulmonary disease (COPD) varied between 1.7-2.7% in the four areas. Among individuals with respiratory symptoms, the prevalence of asthma was most common in Norrbotten, while a diagnosis of COPD or CB was most common in Västra Götaland and Seinäjoki-Vaasa. More women than men with respiratory symptoms reported a diagnosis of asthma in Sweden and Seinäjoki-Vaasa but there were no sex differences in Helsinki. In Sweden, more women than men with symptoms of cough or phlegm reported a diagnosis of CB or COPD, while in Finland the opposite was found. Conclusion: The prevalence of respiratory symptoms and corresponding diagnoses varied between and within the countries. The proportion reporting a diagnosis of obstructive airway disease among individuals with respiratory symptoms varied, indicating differences in diagnostic patterns both between areas and by sex.
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| 8. |
- Axelsson, Malin, et al.
(författare)
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Sleep disturbances and physical inactivity impair health related quality of life in adult asthmatics
- 2017
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Sleep disturbances and physical inactivity have only sparsely been studied in relation to health related quality of life (HRQL) in adult asthmatics. Aim: to investigate sleep disturbances and physical inactivity in relation to HRQL in adult asthmatics. Method: The sample (n=737), aged between 21 and 85 years, selected from the OLIN-studies participated in structured interviews about respiratory health, sleep, physical activity and questionnaires on mental and physical HRQL. Results: Sleep disturbances were more common in asthmatics than in non-asthmatics: snoring (p=0.018), difficulties falling asleep (p=0.025), many nocturnal awakenings (p=0.001), daytime sleepiness (p=0.001), early awakenings (p=0.002). Lower mental HRQL was found in asthmatics with difficulties falling asleep (p=0.001), in asthmatics reporting daytime sleepiness (p=0.010) than asthmatics without sleep disturbances. Lower physical HRQL was found in asthmatics with daytime sleepiness (p=0.002), early awakenings (p=0.001) and many nocturnal awakenings (p=0.039) than asthmatics without these sleep disturbances. Lower physical HRQL was found in physically inactive asthmatics than in physically active asthmatics (p=0.034). Physical activity (p=0.008) and asthma control (p=0.049) were stronger predictors of low physical HRQL than sleep disturbances. Difficulties falling asleep (p=0.001) and many nocturnal awakenings (p=0.04) were identified as negative predictors of mental HRQL while asthma control was a non-significant predictor. Conclusion: Helping adult asthmatics to improve their sleeping habits and to increase their physical activity will have a positive impact on their HRQL. Malin Axelssona, Mai Leanderb, Helena Backmanc, Linnea Hedmanc, Eva Rönmarkc a Department of Care Science, Faculty of Health and Society, Malmö University, Malmö, Sweden b Department of Medical Sciences, Respiratory Medicine and Allergology, Uppsala University, Uppsala, Sweden c Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine, The OLIN Unit, Umeå University, Umeå, Sweden
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