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  • Pearce, Neil E, et al. (författare)
  • IARC Monographs : 40 Years of Evaluating Carcinogenic Hazards to Humans
  • 2015
  • Ingår i: Journal of Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 123:6, s. 507-514
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Recently the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also the approach used to perform these evaluations. Some critics have claimed that IARC Working Groups' failures to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans.OBJECTIVES: The authors of this paper are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We have examined here criticisms of the IARC classification process to determine the validity of these concerns. We review the history of IARC evaluations and describe how the IARC evaluations are performed.DISCUSSION: We conclude that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various discipline and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed.CONCLUSIONS: The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public's health.
  • Gustavsson, A, et al. (författare)
  • Clinical trial : colectomy after resue therapy in ulcerative colitis-3-year follow-up of the Swedish-Danish controlled infliximab study
  • 2010
  • Ingår i: Alimentary Pharmacology and Therapeutics. - : Blackwell Publishing Ltd. - 0269-2813 .- 1365-2036. ; 32:8, s. 984-989
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The long-term efficacy of infliximab as rescue therapy in steroid-refractory ulcerative colitis is not well described. AIM: To examine the long-term efficacy of infliximab as a rescue therapy through a 3-year follow-up of a previous placebo-controlled trial of infliximab in acute steroid-refractory ulcerative colitis. METHOD: In the original study, 45 patients were randomized to a single infusion of infliximab 5 mg/kg or placebo, and at 3 months, 7/24 patients given infliximab were operated vs. 14/21 patients given placebo. Three years or later, patients were asked to participate in a clinical follow-up. RESULTS: Another seven patients underwent colectomy during follow-up: five in the infliximab group and two in the placebo group. After 3 years, a total of 12/24 (50%) patients given infliximab and 16/21 (76%) given placebo (P = 0.012) had a colectomy. None of eight patients in endoscopic remission at 3 months later had a colectomy compared with 7/14 (50%) patients who were not in remission (P=0.02). There was no mortality. CONCLUSION: The benefit of rescue therapy with infliximab in steroid-refractory acute ulcerative colitis remained after 3 years. The main advantage of infliximab treatment occurred during the first 3 months, whereas subsequent colectomy rates were similar in the two groups. Mucosal healing at 3 months influenced later risk of colectomy.
  • Gad, Helge, et al. (författare)
  • MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
  • 2014
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
  • 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.
  • Alhamdow, A., et al. (författare)
  • Fluorene exposure among PAH-exposed workers is associated with epigenetic markers related to lung cancer
  • 2020
  • Ingår i: Occupational and Environmental Medicine. - : BMJ Publishing Group Ltd. - 1351-0711 .- 1470-7926. ; 77:7, s. 488-495
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Exposure to high-molecular-weight polycyclic aromatic hydrocarbons (PAHs) may cause cancer in chimney sweeps and creosote-exposed workers, however, knowledge about exposure to low-molecular-weight PAHs in relation to cancer risk is limited. In this study, we aimed to investigate occupational exposure to the low-molecular-weight PAHs phenanthrene and fluorene in relation to different cancer biomarkers. Methods We recruited 151 chimney sweeps, 19 creosote-exposed workers and 152 unexposed workers (controls), all men. We measured monohydroxylated metabolites of phenanthrene and fluorene in urine using liquid chromatography coupled to tandem mass spectrometry. We measured, in peripheral blood, the cancer biomarkers telomere length and mitochondrial DNA copy number using quantitative PCR; and DNA methylation ofF2RL3andAHRRusing pyrosequencing. Results Median PAH metabolite concentrations were higher among chimney sweeps (up to 3 times) and creosote-exposed workers (up to 353 times), compared with controls (p<0.001; adjusted for age and smoking). n-ary sumation OH-fluorene (sum of 2-hydroxyfluorene and 3-hydroxyfluorene) showed inverse associations with percentage DNA methylation ofF2RL3andAHRRin chimney sweeps (B (95% CI)=-2.7 (-3.9 to -1.5) forF2RL3_cg03636183, and -7.1 (-9.6 to -4.7) forAHRR_cg05575921: adjusted for age and smoking), but not in creosote-exposed workers. In addition, n-ary sumation OH-fluorene showed a 42% mediation effect on the inverse association between being a chimney sweep and DNA methylation ofAHRRCpG2. Conclusions Chimney sweeps and creosote-exposed workers were occupationally exposed to low-molecular-weight PAHs. Increasing fluorene exposure, among chimney sweeps, was associated with lower DNA methylation ofF2RL3andAHRR, markers for increased lung cancer risk. These findings warrant further investigation of fluorene exposure and toxicity.
  • Bujacz, Aleksandra, et al. (författare)
  • Psychosocial working conditions of shiftworking nurses : A long-term latent transition analysis
  • 2021
  • Ingår i: Journal of Nursing Management. - : John Wiley and Sons Inc. - 0966-0429 .- 1365-2834. ; 29:8, s. 2603-2610
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: This study aimed to identify profiles of working conditions to which nurses were exposed to over time and investigate how changes in working conditions relate to shiftworking and health.Background: Previous studies rarely addressed the issue of working conditions development over long periods and the effects of such development on nurses' health.Methods: Data from a national cohort of nurses in Sweden (N = 2936) were analysed using a person-centred analytical approach-latent profile and latent transition analysis.Results: Nurses report better psychosocial working conditions as they progress into mid-career. Shiftworking nurses experience poorer working conditions than their dayworking counterparts and tend to move from shiftwork to daywork as they progress into mid-career. In mid-career, nurses in work environments characterized by low autonomy and support tend to report poorer health outcomes.Conclusion: Current analyses suggest that shiftworking nurses are particularly in need of interventions that address poor work environments. Not only do they experience more negative psychosocial working conditions than their dayworking counterparts, but they do so while having to contend with demanding schedules. Implications for Nursing Management The findings highlight that organisational interventions should target different aspects of the work environment for nurses in diverse stages of their careers.
  • Shrestha, S., et al. (författare)
  • The use of ICD codes to identify IBD subtypes and phenotypes of the Montreal classification in the Swedish National Patient Register
  • 2020
  • Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 55:4, s. 430-435
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Whether data on International Classification of Diseases (ICD)-codes from the Swedish National Patient Register (NPR) correctly correspond to subtypes of inflammatory bowel disease (IBD) and phenotypes of the Montreal classification scheme among patients with prevalent disease is unknown. Materials and methods: We obtained information on IBD subtypes and phenotypes from the medical records of 1403 patients with known IBD who underwent biological treatment at ten Swedish hospitals and retrieved information on their IBD-associated diagnostic codes from the NPR. We used previously described algorithms to define IBD subtypes and phenotypes. Finally, we compared these register-generated subtypes and phenotypes with the corresponding information from the medical records and calculated positive predictive values (PPV) with 95% confidence intervals. Results: Among patients with clinically confirmed disease and diagnostic listings of IBD in the NPR (N = 1401), the PPV was 97 (96-99)% for Crohn's disease, 98 (97-100)% for ulcerative colitis, and 8 (4-11)% for IBD-unclassified. The overall accuracy for age at diagnosis was 95% (when defined as A1, A2, or A3). Examining the validity of codes representing disease phenotype, the PPV was 36 (32-40)% for colonic Crohn's disease (L2), 61 (56-65)% for non-stricturing/non-penetrating Crohn's disease behaviour (B1) and 83 (78-87)% for perianal disease. Correspondingly, the PPV was 80 (71-89)% for proctitis (E1)/left-sided colitis (E2) in ulcerative colitis. Conclusions: Among people with known IBD, the NPR is a reliable source of data to classify most subtypes of prevalent IBD, even though misclassification commonly occurred in Crohn's disease location and behaviour and also among IBD-unclassified patients.
  • Öhrn, Angelica, et al. (författare)
  • Elastic scattering of 96 MeV neutrons from iron, yttrium, and lead
  • 2008
  • Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 77:2, s. 024605-
  • Tidskriftsartikel (refereegranskat)abstract
    • Data on elastic scattering of 96 MeV neutrons from Fe-56, Y-89, and Pb-208 in the angular interval 10-70 degrees are reported. The previously published data on Pb-208 have been extended, as a new method has been developed to obtain more information from data, namely to increase the number of angular bins at the most forward angles. A study of the deviation of the zero-degree cross section from Wick's limit has been performed. It was shown that the data on Pb-208 are in agreement with Wick's limit while those on the lighter nuclei overshoot the limit significantly. The results are compared with modern optical model predictions, based on phenomenology and microscopic nuclear theory. The data on Fe-56, Y-89, and Pb-208 are in general in good agreement with the model predictions.
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