| 1. |
- Al-Jebari, Yahia, et al.
(författare)
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Cancer therapy and risk of congenital malformations in children fathered by men treated for testicular germ-cell cancer : A nationwide register study
- 2019
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Ingår i: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 16:6
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Tidskriftsartikel (refereegranskat)abstract
- Background Because of the potential mutagenic effects of chemo- and radiotherapy, there is concern regarding increased risk of congenital malformations (CMs) among children of fathers with cancer. Previous register studies indicate increased CM risk among children conceived after paternal cancer but lack data on oncological treatment. Increased CM risk was recently reported in children born before paternal cancer. This study aims to investigate whether anti-neoplastic treatment for testicular germ-cell cancer (TGCC) implies additional CM risk. Methods and findings In this nationwide register study, all singletons born in Sweden 1994-2014 (n = 2,027,997) were included. Paternal TGCC diagnoses (n = 2,380), anti-neoplastic treatment, and offspring CMs were gathered from the Swedish Norwegian Testicular Cancer Group (SWENOTECA) and the Swedish Medical Birth Register. Children were grouped based on +/- paternal TGCC; treatment regimen: surveillance (n = 1,340), chemotherapy (n = 2,533), or radiotherapy (n = 360); and according to time of conception: pre- (n = 2,770) or post-treatment (n = 1,437). Odds ratios (ORs) for CMs were calculated using logistic regression with adjustment for parental ages, maternal body mass index (BMI), and maternal smoking. Children conceived before a specific treatment acted as reference for children conceived after the same treatment. Among children fathered by men with TGCC (n = 4,207), 184 had a CM. The risk of malformations was higher among children of fathers with TGCC compared with children fathered by men without TGCC (OR 1.28, 95% confidence interval [CI] 1.19-1.38, p = 0.001, 4.4% versus 3.5%). However, no additional risk increase was associated with oncological treatment when comparing post-treatment-to pretreatment-conceived children (chemotherapy, OR = 0.82, 95% CI 0.54-1.25, p = 0.37, 4.1% versus 4.6%; radiotherapy, OR = 1.01, 95% CI 0.25-4.12, p = 0.98, 3.2% versus 3.0%). Study limitations include lack of data on use of cryopreserved or donor sperm and on seminoma patients for the period 1995-2000-both tending to decrease the difference between the groups with TGCC and without TGCC. Furthermore, the power of analyses on chemotherapy intensity and radiotherapy was limited. Conclusions No additional increased risk of CMs was observed in children of men with TGCC treated with radio- or chemotherapy. However, paternal TGCC per se was associated with modestly increased risk for offspring malformations. Clinically, this information can reassure concerned patients.
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| 2. |
- Ali, Imran, et al.
(författare)
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Exposure to polychlorinated biphenyls and prostate cancer : population-based prospective cohort and experimental studies
- 2016
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Ingår i: Carcinogenesis. - : Oxford University Press. - 0143-3334 .- 1460-2180. ; 37:12, s. 1144-1151
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Tidskriftsartikel (refereegranskat)abstract
- Polychlorinated biphenyls (PCBs) are highly persistent environmental pollutants and are undesirable components of our daily food. PCBs are classified as human carcinogens, but the evidence for prostate cancer is limited and available data are inconsistent. We explored the link between non-dioxin-like PCB and grade of prostate cancer in a prospective cohort as well as in cell experiments. A population-based cohort of 32496 Swedish men aged 45-79 years was followed prospectively through 1998-2011, to assess the association between validated estimates of dietary PCB exposure and incidence of prostate cancer by grade (2789 cases, whereof 1276 low grade, 756 intermediate grade, 450 high grade) and prostate cancer mortality (357 fatal cases). In addition, we investigated a non-dioxin-like PCB153-induced cell invasion and related markers in normal prostate stem cells (WPE-stem) and in three different prostate cancer cell lines (PC3, DU145 and 22RV1) at exposure levels relevant to humans. After multivariable-adjustment, dietary PCB exposure was positively associated with high-grade prostate cancer, relative risk (RR) 1.35 [95% confidence interval (CI): 1.03-1.76] and with fatal prostate cancer, RR 1.43 (95% CI: 1.05-1.95), comparing the highest tertile with the lowest. We observed no association with low or intermediate grade of prostate cancer. Cell invasion and related markers, including MMP9, MMP2, Slug and Snail, were significantly increased in human prostate cancer cells as well as in prostate stem cells after exposure to PCB153. Our findings both from the observational and experimental studies suggest a role of non-dioxin-like PCB153 in the development of high-grade and fatal prostate cancer.
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| 3. |
- Berglund, Anders, et al.
(författare)
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Customer adapted grading of Scots pine sawn timber using a multivariate method
- 2015
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Ingår i: Scandinavian Journal of Forest Research. - : Informa UK Limited. - 0282-7581 .- 1651-1891. ; 30:1, s. 87-97
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Tidskriftsartikel (refereegranskat)abstract
- To define new grading rules, or to customize the ones in use in a rule-based automatic grading system of boards, is a time-consuming job for a sawmill engineer. This has the effect that changes are rarely made. The objective of this study was to continue the development of a method that replaces the calibration of grading rule settings by a holistic-subjective automatic grading, using multivariate models. The objective was also to investigate if this approach can improve sawmill profitability and at the same time have a satisfied customer. For the study, 323 Scots pine (Pinus sylvestris L.) boards were manually graded according to preferences of an important customer. That is, a customer that regularly purchases significant volumes of sawn timber. This manual grading was seen as reference grading in this work. The same boards were also scanned and graded by a rule-based automatic grading system, calibrated for the same customer. Multivariate models for prediction of board grade based on aggregated knot variables, obtained from the scanning, were calibrated using partial least squares regression. The results show that prediction of board grades by the multivariate models were more correct, with respect to the manual grading, than the grading by the rule-based automatic grading system. The prediction of board grades based on multivariate models resulted in 76-87% of the boards graded correctly, according to the manual grading, while the corresponding number was 63% for the rule-based automatic grading system.
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| 4. |
- Berglund, Malin, et al.
(författare)
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Myringoplasty Outcomes From the Swedish National Quality Registry
- 2017
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Ingår i: The Laryngoscope. - : John Wiley & Sons. - 0023-852X .- 1531-4995. ; 127:10, s. 2389-2395
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES/HYPOTHESIS: Data from patients registered for myringoplasty during 2002 to 2012 in the Swedish National Quality Registry for Myringoplasty.STUDY DESIGN: Both conventional myringoplasty and fat-graft techniques were used aimed at healing the tympanic membrane in noninfected ears.METHODS: Analysis was performed on data in a national database collected from 32 ear, nose, and throat clinics. Surgical procedures and outcomes, and patient satisfaction from a questionnaire were studied.RESULTS: The database was comprised of 3,775 surgical procedures, with follow-up available for analysis. One-third were children under the age of 15 years. The most common indication for surgery was infection prophylaxis. The overall healing rate of the tympanic membrane after surgery was 88.5%, with a high mean patient satisfaction. Complications registered were postoperative infection, tinnitus, or taste disturbance that occurred in 5.8% of patients.CONCLUSIONS: Swedish results for a large number of patients who completed myringoplasty are presented. The success rate in this study is comparable to other studies, and good patient-reported outcome measures of myringoplasty are presented. Databases for surgical procedures and clinical audits are systematic processes for continuous learning in healthcare. This study shows that clinical databases can be utilized to analyze national results of surgical procedures.LEVEL OF EVIDENCE: 2b Laryngoscope, 127:2389-2395, 2017.
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| 5. |
- Berglund, Malin, 1970, et al.
(författare)
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Tinnitus and taste disturbances reported after myringoplasty: Data from a national quality registry
- 2019
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Ingår i: Laryngoscope. - : Wiley. - 0023-852X .- 1531-4995. ; 129:1, s. 209-215
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Tidskriftsartikel (refereegranskat)abstract
- © 2018 The American Laryngological, Rhinological and Otological Society, Inc. Objectives/Hypothesis: Postoperative tinnitus and taste disturbances after myringoplasty are more common than previously reported. Study Design: This study was a retrospective analysis of prospectively collected data from the Swedish National Quality Registry for Myringoplasty. Methods: The analysis was performed on extracted data from all counties in Sweden collected from database A from 2002 to 2012 and database B from 2013 to 2016. Tinnitus and taste disturbance complications 1 year after myringoplasty were analyzed in relation to gender, age, procedure, and success rate. In database A, physicians reported tinnitus and taste disturbances. In database B, patients reported the complications. Results: A major difference was found when the complications were reported by physicians compared to when the complications were reported by patients. In database A, tinnitus was reported in 1.2% of the patients and taste disturbances in 0.5%. In database B, the frequencies were 12.3% and 11.2%, respectively. Tinnitus and taste disturbances were more frequent after conventional myringoplasty compared to those after fat grafting and were more frequent after primary compared to those after revision surgery when reported by physicians. Patients, however, reported the same frequency of tinnitus after fat graft myringoplasty compared to that after conventional myringoplasty (12.0% vs. 12.6%) and fewer taste disturbances after revision surgery. In follow-up assessments, complications persisted after surgery over a long time period. Conclusion: Tinnitus and taste disturbances are more common after myringoplasty when patients report their symptoms than when physicians report the symptoms. Level of Evidence: 2b. Laryngoscope, 2018.
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| 6. |
- Boström, Marja L., et al.
(författare)
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Bioaccumulation and Trophodynamics of the Antidepressants Sertraline and Fluoxetine in Laboratory-Constructed, 3-Level Aquatic Food Chains
- 2017
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Ingår i: Environmental Toxicology and Chemistry. - : John Wiley & Sons. - 0730-7268 .- 1552-8618. ; 36:4, s. 1029-1037
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Tidskriftsartikel (refereegranskat)abstract
- Although reports of pharmaceutical bioconcentration in aquatic organisms are increasing, less is known about trophic transfer in aquatic food webs. The bioaccumulation and trophodynamics of sertraline and fluoxetine, 2 selective serotonin reuptake inhibitors (SSRIs) frequently detected in aquatic environments, were tested by exposing constructed aquatic food chains to SSRIs under controlled laboratory conditions. Both of these ionizable, weak base pharmaceuticals showed lower bioaccumulation factors (BAFs) with increasing trophic level (i.e., no biomagnifications) in 2 3-level food chains (Acer platanoides, fed to Asellus aquaticus, in turn fed to Notonecta glauca or Pungitius pungitius). Mean sertraline BAFs in A. platanoides, A. aquaticus, N. glauca, and P. pungitus were 2200L/kg, 360L/kg, 26L/kg, and 49L/kg, respectively, and mean fluoxetine BAFs 1300L/kg, 110L/kg, 11L/kg, and 41L/kg, respectively. The weak influence of diet was further demonstrated by measured BAFs being equal to or lower than measured bioconcentration factors (BCFs). Organism lipid content was not positively correlated with BAFs, suggesting that other processes are driving interspecific differences in SSRI bioaccumulation. The empirically derived parameter values were introduced into a proposed bioaccumulation model, and a poor correlation was found between modeled and empirical BAFs (predicted r(2)=-0.63). In conclusion, the apparent lack of biomagnification of these ionizable pharmaceuticals suggests that environmental concern should not necessarily focus only on higher trophic levels, but also on species showing high BCFs at any trophic level.
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| 7. |
- Boström, Marja L., et al.
(författare)
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Influence of pH-dependent aquatic toxicity of ionizable pharmaceuticals on risk assessments over environmental pH ranges.
- 2015
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Ingår i: Water Research. - : Elsevier BV. - 1879-2448 .- 0043-1354. ; 72:Online 6 September 2014, s. 154-161
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Tidskriftsartikel (refereegranskat)abstract
- Due to variation in pH, ionizable pharmaceuticals entering aquatic environments experience different degrees of ionization, which may affect toxicity. Using data from toxicity testing at only neutral pH may potentially under- or overestimate actual toxicity at pH ranges found in natural aquatic environments. Here we show relative pH-dependent acute toxicity to Daphnia magna for the pharmaceutical weak bases fluoxetine and sertraline, as well as the weak acids naproxen, diclofenac, ibuprofen and ketoprofen. A probabilistic modelling approach using the pH-dependent toxicity data for D. magna and an environmental pH distribution based on over 4000 European running waters from 21 countries predicted that environmental toxicity for the weak bases may be underestimated if pH 7 was assumed. The model predicted median underestimation by a factor of 3, with 90% of the model results ranging from 1 to 6. Consequently, due to the slightly basic nature of the European running waters, weak acid toxicity may be overestimated by a factor of 2. Predicted median toxicity was 0.5 of that assuming pH 7 with 90% of the results ranging from 0.03 to 5. Because aquatic pH exhibits large variation both within and between countries, we advise the use of site-specific risk assessments for ionizable pharmaceuticals in making informed water management decisions.
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| 8. |
- Eriksson, Olof, et al.
(författare)
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Metabolically Active Brown Adipose Tissue Is Found in Adult Subjects with Type 1 Diabetes.
- 2019
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 20:23
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Tidskriftsartikel (refereegranskat)abstract
- Type 1 diabetes (T1D) is characterized by the loss of insulin-producing cells and hence insulin secretion and metabolic control. In addition to insulin, there are a number of hormones and cytokines that influence metabolism, and many of these can be secreted from brown adipose tissue (BAT). However, the presence and activity of BAT in T1D have not been studied, despite the fact that preclinical studies have shown that transplantation of BAT in mouse models of T1D can restore metabolic control. The metabolic activity of BAT, white adipose tissue (WAT), and skeletal muscle was investigated in patients with T1D (n = 11) by 2-deoxy-2-(18F)fluoro-D-glucose PET/CT after cold stimulation. Functional BAT was detected in 4 out of 11 individuals with T1D with a prevalence of 36%. The glucose utilization rate in the supraclavicular BAT regions ranged from 0.75-38.7 µmol × min-1 × 100 g-1. The glucose utilization per gram tissue was higher in BAT when compared with both WAT (p = 0.049) and skeletal muscle (p = 0.039). However, no correlation between BAT activity and metabolic control or insulin requirements was found. In conclusion, for the first time, cold-induced BAT was detected in patients with T1D with a wide range in metabolic activity. Contrary to findings in animal models, the metabolic activity of BAT had negligible impact on insulin requirements or metabolic control in T1D under normal physiological conditions.
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| 9. |
- Erlandsson, Johan, et al.
(författare)
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Optimal fractionation of preoperative radiotherapy and timing to surgery for rectal cancer (Stockholm III): a multicentre, randomised, non-blinded, phase 3, non-inferiority trial
- 2017
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Ingår i: The Lancet Oncology. - : ELSEVIER SCIENCE INC. - 1470-2045 .- 1474-5488. ; 18:3, s. 336-346
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Tidskriftsartikel (refereegranskat)abstract
- Background Radiotherapy reduces the risk of local recurrence in rectal cancer. However, the optimal radiotherapy fractionation and interval between radiotherapy and surgery is still under debate. We aimed to study recurrence in patients randomised between three different radiotherapy regimens with respect to fractionation and time to surgery. Methods In this multicentre, randomised, non-blinded, phase 3, non-inferiority trial (Stockholm III), all patients with a biopsy-proven adenocarcinoma of the rectum, without signs of non-resectability or distant metastases, without severe cardiovascular comorbidity, and planned for an abdominal resection from 18 Swedish hospitals were eligible. Participants were randomly assigned with permuted blocks, stratified by participating centre, to receive either 5 x 5 Gy radiation dose with surgery within 1 week (short-course radiotherapy) or after 4-8 weeks (short-course radiotherapy with delay) or 25 x 2 Gy radiation dose with surgery after 4-8 weeks (long-course radiotherapy with delay). After a protocol amendment, randomisation could include all three treatments or just the two short-course radiotherapy treatments, per hospital preference. The primary endpoint was time to local recurrence calculated from the date of randomisation to the date of local recurrence. Comparisons between treatment groups were deemed non-inferior if the upper limit of a double-sided 90% CI for the hazard ratio (HR) did not exceed 1.7. Patients were analysed according to intention to treat for all endpoints. This study is registered with ClinicalTrials.gov, number NCT00904813. Findings Between Oct 5, 1998, and Jan 31, 2013, 840 patients were recruited and randomised; 385 patients in the three-arm randomisation, of whom 129 patients were randomly assigned to short-course radiotherapy, 128 to short-course radiotherapy with delay, and 128 to long-course radiotherapy with delay, and 455 patients in the two-arm randomisation, of whom 228 were randomly assigned to short-course radiotherapy and 227 to short-course radiotherapy with delay. In patients with any local recurrence, median time from date of randomisation to local recurrence in the pooled short-course radiotherapy comparison was 33.4 months (range 18.2-62.2) in the short-course radiotherapy group and 19.3 months (8.5-39.5) in the short-course radiotherapy with delay group. Median time to local recurrence in the long-course radiotherapy with delay group was 33.3 months (range 17.8-114.3). Cumulative incidence of local recurrence in the whole trial was eight of 357 patients who received short-course radiotherapy, ten of 355 who received short-course radiotherapy with delay, and seven of 128 who received long-course radiotherapy (HR vs short-course radiotherapy: short-course radiotherapy with delay 1.44 [95% CI 0.41-5.11]; long-course radiotherapy with delay 2.24 [0.71-7.10]; p=0.48; both deemed non-inferior). Acute radiation-induced toxicity was recorded in one patient (amp;lt;1%) of 357 after short-course radiotherapy, 23 (7%) of 355 after short-course radiotherapy with delay, and six (5%) of 128 patients after long-course radiotherapy with delay. Frequency of postoperative complications was similar between all arms when the three-arm randomisation was analysed (65 [50%] of 129 patients in the short-course radiotherapy group; 48 [38%] of 128 patients in the short-course radiotherapy with delay group; 50 [39%] of 128 patients in the long-course radiotherapy with delay group; odds ratio [OR] vs short-course radiotherapy: short-course radiotherapy with delay 0.59 [95% CI 0.36-0.97], long-course radiotherapy with delay 0.63 [0.38-1.04], p=0.075). However, in a pooled analysis of the two short-course radiotherapy regimens, the risk of postoperative complications was significantly lower after short-course radiotherapy with delay than after short-course radiotherapy (144 [53%] of 355 vs 188 [41%] of 357; OR 0.61 [95% CI 0.45-0.83] p=0.001). Interpretation Delaying surgery after short-course radiotherapy gives similar oncological results compared with short-course radiotherapy with immediate surgery. Long-course radiotherapy with delay is similar to both short-course radiotherapy regimens, but prolongs the treatment time substantially. Although radiation-induced toxicity was seen after short-course radiotherapy with delay, postoperative complications were significantly reduced compared with short-course radiotherapy. Based on these findings, we suggest that short-course radiotherapy with delay to surgery is a useful alternative to conventional short-course radiotherapy with immediate surgery.
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| 10. |
- Fredriksson, Magnus, et al.
(författare)
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Validating a crosscutting simulation program based on computed tomography scanning of logs
- 2015
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Ingår i: European Journal of Wood and Wood Products. - : Springer Science and Business Media LLC. - 0018-3768 .- 1436-736X. ; 73:2, s. 143-150
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Tidskriftsartikel (refereegranskat)abstract
- Wood scanners and software for calculating crosscutting positions have been used in the wood industry for some years now. The scanners are used to detect biological and geometrical deviations on the sawn timber, which makes it possible to remove undesired defects using crosscut saws. Yield calculations for crosscutting have not been investigated to the same extent as sawing yield calculations for primary breakdown of logs, especially if the whole chain from log to end product is considered. The objective of this study was to validate the result of a computer program developed for simulating crosscutting of boards. The crosscut simulations were performed with respect to knot characteristics on Scots pine (Pinus sylvestris L.) board surfaces. Validating a crosscutting simulation program would mean that it can be used to investigate how raw material and customization of quality rules affect the yield in a wood production chain from log to crosscut end product. The validation showed that crosscutting yield for boards could be predicted with a root mean square error of 13 percentage points, and the technique can be used to identify unsuitable logs for a certain product at an early stage of production.
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