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- Hansson, Gert-Åke, et al.
(författare)
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Questionnaire versus direct technical measurements in assessing postures and movements of the head, upper back, arms and hands
- 2001
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Ingår i: Scandinavian Journal of Work, Environment and Health. - 0355-3140. ; 27:1, s. 30-40
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: This study compares questionnaire-assessed exposure data on work postures and movements with direct technical measurements. METHODS: Inclinometers and goniometers were used to make full workday measurements of 41 office workers and 41 cleaners, stratified for such factors as musculoskeletal complaints. The subjects answered a questionnaire on work postures of the head, back, and upper arms and repeated movements of the arms and hands (3-point scales). The questionnaire had been developed on the basis of a previously validated one. For assessing worktasks and their durations, the subjects kept a 2-week worktask diary. Job exposure was individually calculated by time-weighting the task exposure measurements according to the diary. RESULTS: The agreement between the self-assessed and measured postures and movements was low (kappa = 0.06 for the mean within the occupational groups and kappa = 0.27 for the whole group). Cleaners had a higher measured workload than office workers giving the same questionnaire response. Moreover, the subjects with neck-shoulder complaints rated their exposure to movements as higher than those without complaints but with the same measured mechanical exposure. In addition, these subjects also showed a general tendency to rate their postural exposure as higher. The women rated their exposure higher than the men did. CONCLUSIONS: The questionnaire-assessed exposure data had low validity. For the various response categories the measured exposure depended on occupation. Furthermore, there was a differential misclassification due to musculoskeletal complaints and gender. Thus it seems difficult to construct valid questionnaires on mechanical exposure for establishing generic exposure-response relations in epidemiologic studies, especially cross-sectional ones. Direct technical measurements may be preferable.
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- Mohell, N., et al.
(författare)
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APR-246 overcomes resistance to cisplatin and doxorubicin in ovarian cancer cells
- 2015
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Ingår i: Cell Death and Disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Two main causes of platinum resistance are mutation in the tumor suppressor gene TP53 and drug-induced increase in intracellular glutathione concentration. Mutations in TP53 occur in about 50% of human tumors. APR-246 (PRIMA-1(MET)) is the first clinical-stage compound that reactivates mutant p53 and induces apoptosis. APR-246 is a prodrug that is converted to the active compound methylene quinuclidinone (MQ), a Michael acceptor that binds to cysteine residues in mutant p53 and restores its wildtype conformation. Here, we show that MQ also binds to cysteine in glutathione, thus decreasing intracellular free glutathione concentration. We also show that treatment with APR-246 completely restores the cisplatin and doxorubicin sensitivity to p53-mutant drug-resistant ovarian cancer cells. We propose that this unique ability of APR-246/MQ to bind to cysteines in both mutant p53 and glutathione has a key role in the resensitization as well as in the outstanding synergistic effects observed with APR-246 in combination with platinum compounds in ovarian cancer cell lines and primary cancer cells. However, MQ binding to cysteines in other targets, for example, thioredoxin reductase, may contribute as well. Strong synergy was also observed with the DNA-damaging drugs doxorubicin and gemcitabine, while additive effects were found with the taxane docetaxel. Our results provide a strong rationale for the ongoing clinical study with APR-246 in combination with platinum-based therapy in patients with p53-mutant recurrent high-grade serous (HGS) ovarian cancer. More than 96% of these patients carry TP53 mutations. Combined treatment with APR-246 and platinum or other DNA-damaging drugs could allow dramatically improved therapy of a wide range of therapy refractory p53 mutant tumors.
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- Wahlstrom, E., et al.
(författare)
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Size-dependent foraging efficiency, cannibalism and zooplankton community structure
- 2000
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Ingår i: Oecologia. ; 123:1, s. 138-148
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Tidskriftsartikel (refereegranskat)abstract
- To examine size-dependent food web interactions in systems with cannibalism, we compared the abundances of zooplankton and phytoplankton over 2 years in four lakes with cannibalistic perch (Perca fluviatilis ) of which two also supported the top predator pike (Esox lucius). The abundance of perch 2 years and older was lower in lakes with pike than in lakes with only perch. In contrast, the abundance of small perch (young-of-the-year and I-year old) was lower in lakes with only perch suggesting that intense cannibalism reduced these size classes to low levels in lakes lacking pike. Functional response experiments with differently sized perch and zooplankton showed that the attack rate of small perch susceptible to cannibalism was much higher than that of large cannibalising perch. The optimal body size of perch with respect to attack rate was also lower for small zooplankton prey than for large zooplankton. The zooplankton communities in lakes with only perch were dominated by the relatively small species Ceriodaphnia quadrangula and Bosmina spp. and total zooplankton biomass was higher in these lakes than in lakes with both pike and perch. In contrast, the mean size of cladoceran zooplankton was largest in lakes with both pike and perch owing to a dominance of the large zooplankton species Holopedium gibberum in these lakes. We relate these patterns to (1) the low foraging efficiency of large perch on small zooplankton and (2) the low abundance of small zooplanktivorous perch (due to cannibalism) in lakes with only perch. The differences in zooplankton community structure also resulted in different seasonal dynamics of phytoplankton between lakes. Cannibalism introduces a vertical heterogeneity to food webs that causes consumer-resource dynamics that are not predictable from linear food chain models.
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