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- Gad, Helge, et al.
(författare)
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MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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| 2. |
- Aasa, Mikael, et al.
(författare)
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Cost and health outcome of primary percutaneous coronary intervention versus thrombolysis in acute ST-segment elevation myocardial infarction-Results of the Swedish Early Decision reperfusion Study (SWEDES) trial.
- 2010
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Ingår i: American heart journal. - : Elsevier BV. - 1097-6744 .- 0002-8703. ; 160:2, s. 322-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In ST-elevation myocardial infarction, primary percutaneous coronary intervention (PCI) has a superior clinical outcome, but it may increase costs in comparison to thrombolysis. The aim of the study was to compare costs, clinical outcome, and quality-adjusted survival between primary PCI and thrombolysis. METHODS: Patients with ST-elevation myocardial infarction were randomized to primary PCI with adjunctive enoxaparin and abciximab (n = 101), or to enoxaparin followed by reteplase (n = 104). Data on the use of health care resources, work loss, and health-related quality of life were collected during a 1-year period. Cost-effectiveness was determined by comparing costs and quality-adjusted survival. The joint distribution of incremental costs and quality-adjusted survival was analyzed using a nonparametric bootstrap approach. RESULTS: Clinical outcome did not differ significantly between the groups. Compared with the group treated with thrombolysis, the cost of interventions was higher in the PCI-treated group ($4,602 vs $3,807; P = .047), as well as the cost of drugs ($1,309 vs $1,202; P = .001), whereas the cost of hospitalization was lower ($7,344 vs $9,278; P = .025). The cost of investigations, outpatient care, and loss of production did not differ significantly between the 2 treatment arms. Total cost and quality-adjusted survival were $25,315 and 0.759 vs $27,819 and 0.728 (both not significant) for the primary PCI and thrombolysis groups, respectively. Based on the 1-year follow-up, bootstrap analysis revealed that in 80%, 88%, and 89% of the replications, the cost per health outcome gained for PCI will be <$0, $50,000, and $100,000 respectively. CONCLUSION: In a 1-year perspective, there was a tendency toward lower costs and better health outcome after primary PCI, resulting in costs for PCI in comparison to thrombolysis that will be below the conventional threshold for cost-effectiveness in 88% of bootstrap replications.
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| 5. |
- Brechensbauer Brandin, Madeleine, et al.
(författare)
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Centralen : Studier i området kring Stockholms Centralstation
- 1989
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Rapport (populärvet., debatt m.m.)abstract
- Denna skrift handlar om Centralen i Stockholm och dess närmaste omgivningar, Centralplan, T-centralen, Vasagatan och Klarabergsgatan. Den är resultatet av Arkitekturskolans arbete läsåret 1983- 84 och innehåller förutom en rad projekt också historiska utblickar och samtidskritiska resonemang. En stor del av innehållet redovisades redan våren 1984 - det skedde genom en utställning på Arkitekturmuseet och en preliminär publikation. Materialet har sedan svällt ut med innehållsrika uppsatser om Centralen, om äldre och nyare insatser för att förena konst och arkitektur och om den föga kända, ännu obebyggda Blekholmen.
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| 6. |
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| 7. |
- Cöster, Lars, 1945-, et al.
(författare)
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Chronic widespread musculoskeletal pain - A comparison of those who meet criteria for fibromyalgia and those who do not
- 2008
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Ingår i: European Journal of Pain. - : Wiley. - 1090-3801 .- 1532-2149. ; 12:5, s. 600-610
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Tidskriftsartikel (refereegranskat)abstract
- Fibromyalgia is currently classified as chronic widespread pain with widespread allodynia to pressure pain. There are few data describing pain characteristics, quality of life, consequences for daily living, and psychosocial status in patients who meet the classification criteria for fibromyalgia proposed by the American College of Rheumatology compared with patients with chronic widespread pain but not widespread allodynia. This study used a randomly selected sample from the general population. A postal questionnaire and a pain mannequin were sent to 9952 people. The response rate was 76.7%. The pain drawings showed that 345 people had widespread pain, that is, they noted pain in all four extremities and axially. Clinical examination, which included a manual tender point examination, was performed in 125 subjects. These people answered commonly used questionnaires on pain, quality of life, coping strategies, depression, and anxiety. Compared with chronic widespread pain without widespread allodynia, fibromyalgia was associated with more severe symptoms/consequences for daily life and higher pain severity. Similar coping strategies were found. Chronic widespread pain without widespread allodynia to pressure pain was found in 4.5% in the population and fibromyalgia in 2.5%. © 2007 European Federation of Chapters of the International Association for the Study of Pain.
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| 8. |
- Gerdle, Björn, 1953-, et al.
(författare)
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Prevalence of widespread pain and associations with work status : A population study
- 2008
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Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background. This population study based on a representative sample from a Swedish county investigates the prevalence, duration, and determinants of widespread pain (WSP) in the population using two constructs and estimates how WSP affects work status. In addition, this study investigates the prevalence of widespread pain and its relationship to pain intensity, gender, age, income, work status, citizenship, civil status, urban residence, and health care seeking. Methods. A cross-sectional survey using a postal questionnaire was sent to a representative sample (n = 9952) of the target population (284,073 people, 18-74 years) in a county (Östergötland) in the southern Sweden. The questionnaire was mailed and followed by two postal reminders when necessary. Results. The participation rate was 76.7% (n = 7637), the non-participants were on the average younger, earned less money, and male. Women had higher prevalences of pain in 10 different predetermined anatomical regions. WSP was generally chronic (90-94%) and depending on definition of WSP the prevalence varied between 4.8-7.4% in the population. Women had significantly higher prevalence of WSP than men and the age effect appeared to be stronger in women than in men. WSP was a significant negative factor - together with age 50-64 years, low annual income, and non-Nordic citizen - for work status in the community and in the group with chronic pain. Chronic pain but not the spreading of pain was related to health care seeking in the population. Conclusion. This study confirms earlier studies that report high prevalences of widespread pain in the population and especially among females and with increasing age. Widespread pain is associated with prominent effects on work status. © 2008 Gerdle et al, licensee BioMed Central Ltd.
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| 10. |
- Henriksson,, Lars Eric, et al.
(författare)
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Determination of the Nitrogen-Fixing Capacity of Algae in Soil
- 1972
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Ingår i: Oikos. - : JSTOR. - 0030-1299 .- 1600-0706. ; 23:3, s. 420-423
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Tidskriftsartikel (refereegranskat)abstract
- A method to determine the potential of microbial nitrogen fixation in soils under aerobic conditions is described. Four different soil types were studied; loess, lime, mull and calcareous soil. The soil samples were collected in three different areas in Europe.
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