| 1. |
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| 2. |
- Melin, Beatrice, et al.
(författare)
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Known glioma risk loci are associated with glioma with a family history of brain tumours : a case-control gene association study
- 2013
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 132:10, s. 2464-2468
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Tidskriftsartikel (refereegranskat)abstract
- Familial cancer can be used to leverage genetic association studies. Recent genome-wide association studies have reported independent associations between seven single nucleotide polymorphisms (SNPs) and risk of glioma. The aim of this study was to investigate whether glioma cases with a positive family history of brain tumours, defined as having at least one first- or second-degree relative with a history of brain tumour, are associated with known glioma risk loci. One thousand four hundred and thirty-one glioma cases and 2,868 cancer-free controls were identified from four casecontrol studies and two prospective cohorts from USA, Sweden and Denmark and genotyped for seven SNPs previously reported to be associated with glioma risk in casecontrol designed studies. Odds ratios were calculated by unconditional logistic regression. In analyses including glioma cases with a family history of brain tumours (n = 104) and control subjects free of glioma at baseline, three of seven SNPs were associated with glioma risk: rs2736100 (5p15.33, TERT), rs4977756 (9p21.3, CDKN2A-CDKN2B) and rs6010620 (20q13.33, RTEL1). After Bonferroni correction for multiple comparisons, only one marker was statistically significantly associated with glioma risk, rs6010620 (ORtrend for the minor (A) allele, 0.39; 95% CI: 0.250.61; Bonferroni adjusted ptrend, 1.7 x 104). In conclusion, as previously shown for glioma regardless of family history of brain tumours, rs6010620 (RTEL1) was associated with an increased risk of glioma when restricting to cases with family history of brain tumours. These findings require confirmation in further studies with a larger number of glioma cases with a family history of brain tumours.
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| 3. |
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| 5. |
- Brogren, Elisabeth, et al.
(författare)
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Fractures of the distal radius in women aged 50 to 75 years: natural course of patient-reported outcome, wrist motion and grip strength between 1 year and 2-4 years after fracture.
- 2011
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Ingår i: Journal of Hand Surgery: European Volume. - : SAGE Publications. - 2043-6289 .- 1753-1934. ; 36E, s. 568-576
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Tidskriftsartikel (refereegranskat)abstract
- Fractures of the distal radius in postmenopausal women may cause prolonged pain and disability, but little is known about their natural course beyond the first year. In this study, women of 50-75 years of age, initially treated with cast or external fixation, were examined 1 year after distal radial fracture and then re-evaluated after a mean of 3 (range, 2-4) years. The evaluation included pain, disability (DASH) scores, grip strength and range of motion. In the 49 participating women pain scores, grip strength and range of motion improved significantly, although the mean improvement was moderate or small. In a subgroup of 13 patients with moderate or severe malunion, the 1 year DASH score was significantly worse than in the remaining patients but improved significantly together with grip strength and range of motion. After fractures of the distal radius, pain, grip strength and range of motion continued to improve beyond 1 year, up to 2-4 years. Patients with malunion had more disability at 1 year but showed significant improvement at 2-4 years.
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| 6. |
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| 7. |
- Vickers, Andrew J., et al.
(författare)
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Prostate specific antigen concentration at age 60 and death or metastasis from prostate cancer : Case-control study
- 2010
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Ingår i: BMJ (Online). - : BMJ. - 1756-1833 .- 0959-8138 .- 1468-5833. ; 341:7773
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To determine the relation between concentrations of prostate specific antigen at age 60 and subsequent diagnosis of clinically relevant prostate cancer in an unscreened population to evaluate whether screening for prostate cancer and chemoprevention could be stratified by risk. Design: Case-control study with 1:3 matching nested within a highly representative population based cohort study. Setting: General population of Sweden taking part in the Malmo Preventive Project. Cancer registry at the National Board of Health and Welfare. Participants: 1167 men aged 60 who provided blood samples in 1981 and were followed up to age 85. Main outcome measures: Metastasis or death from prostate cancer. Results: The rate of screening during the course of the study was low. There were 43 cases of metastasis and 35 deaths from prostate cancer. Concentration of prostate specific antigen at age 60 was associated with prostate cancer metastasis (area under the curve 0.86, 95% confidence interval 0.79 to 0.92; P<0.001) and death from prostate cancer (0.90, 0.84 to 0.96; P<0.001). The greater the number for the area under the curve (values from 0 to 1) the better the test. Although only a minority of the men with concentrations in the top quarter (>2 ng/ml) develop fatal prostate cancer, 90% (78% to 100%) of deaths from prostate cancer occurred in these men. Conversely, men aged 60 with concentrations at the median or lower (≤1 ng/ml) were unlikely to have clinically relevant prostate cancer (0.5% risk of metastasis by age 85 and 0.2% risk of death from prostate cancer). Conclusions: The concentration of prostate specific antigen at age 60 predicts lifetime risk of metastasis and death from prostate cancer. Though men aged 60 with concentrations below the median (≤1 ng/ml) might harbour prostate cancer, it is unlikely to become life threatening. Such men could be exempted from further screening, which should instead focus on men with higher concentrations.
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| 8. |
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| 9. |
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| 10. |
- Dahlin, Anna M, 1979-, et al.
(författare)
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Colorectal cancer prognosis depends on T-cell infiltration and molecular characteristics of the tumor
- 2011
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Ingår i: Modern Pathology. - : Elsevier BV. - 0893-3952 .- 1530-0285. ; 24, s. 671-682
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to relate the density of tumor infiltrating T cells to cancer-specific survival in colorectal cancer, taking into consideration the CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) screening status. The T-cell marker CD3 was stained by immunohistochemistry in 484 archival tumor tissue samples. T-cell density was semiquantitatively estimated and scored 1-4 in the tumor front and center (T cells in stroma), and intraepithelially (T cells infiltrating tumor cell nests). Total CD3 score was calculated as the sum of the three CD3 scores (range 3-12). MSI screening status was assessed by immunohistochemistry. CIMP status was determined by quantitative real-time PCR (MethyLight) using an eight-gene panel. We found that patients whose tumors were highly infiltrated by T cells (total CD3 score ≥7) had longer survival compared with patients with poorly infiltrated tumors (total CD3 score ≤4). This finding was statistically significant in multivariate analyses (multivariate hazard ratio, 0.57; 95% confidence interval, 0.31-1.00). Importantly, the finding was consistent in rectal cancer patients treated with preoperative radiotherapy. Although microsatellite unstable tumor patients are generally considered to have better prognosis, we found no difference in survival between microsatellite unstable and microsatellite stable (MSS) colorectal cancer patients with similar total CD3 scores. Patients with MSS tumors highly infiltrated by T cells had better prognosis compared with intermediately or poorly infiltrated microsatellite unstable tumors (log rank P=0.013). Regarding CIMP status, CIMP-low was associated with particularly poor prognosis in patients with poorly infiltrated tumors (multivariate hazard ratio for CIMP-low versus CIMP-negative, 3.07; 95% confidence interval, 1.53-6.15). However, some subset analyses suffered from low power and are in need of confirmation by independent studies. In conclusion, patients whose tumors are highly infiltrated by T cells have a beneficial prognosis, regardless of MSI, whereas the role of CIMP status in this context is less clear.
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| 11. |
- Dahlin, Anna M, 1979-, et al.
(författare)
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The role of the CpG island methylator phenotype in colorectal cancer prognosis depends on microsatellite instability screening status
- 2010
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 16:6, s. 1845-1855
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The aim of this study was to relate the CpG island methylator phenotype (CIMP; characterized by extensive promoter hypermethylation) to cancer-specific survival in colorectal cancer, taking into consideration relevant clinicopathologic factors, such as microsatellite instability (MSI) screening status and the BRAF V600E mutation. EXPERIMENTAL DESIGN: Archival tumor samples from 190 patients from the Northern Sweden Health and Disease Study (NSHDS) and 414 patients from the Colorectal Cancer in Umeå Study (CRUMS), including 574 with cancer-specific survival data, were analyzed for an eight-gene CIMP panel using quantitative real-time PCR (MethyLight). MSI screening status was assessed by immunohistochemistry. RESULTS: CIMP-low patients had a shorter cancer-specific survival compared with CIMP-negative patients (multivariate hazard ratio in NSHDS, 2.01; 95% confidence interval, 1.20-3.37; multivariate hazard ratio in CRUMS, 1.48; 95% confidence interval, 1.00-2.22). This result was similar in subgroups based on MSI screening status and was statistically significant in microsatellite stable (MSS) tumors in NSHDS. For CIMP-high patients, a shorter cancer-specific survival compared with CIMP-negative patients was observed in the MSS subgroup. Statistical significance was lost after adjusting for the BRAF mutation, but the main findings were generally unaffected. CONCLUSIONS: In this study, we found a poor prognosis in CIMP-low patients regardless of MSI screening status, and in CIMP-high patients with MSS. Although not consistently statistically significant, these results were consistent in two separate patient groups and emphasize the potential importance of CIMP and MSI status in colorectal cancer research.
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| 12. |
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| 13. |
- Dahlin, Johan
(författare)
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Sequential Monte Carlo for inference in nonlinear state space models
- 2014
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Nonlinear state space models (SSMs) are a useful class of models to describe many different kinds of systems. Some examples of its applications are to model; the volatility in financial markets, the number of infected persons during an influenza epidemic and the annual number of major earthquakes around the world. In this thesis, we are concerned with state inference, parameter inference and input design for nonlinear SSMs based on sequential Monte Carlo (SMC) methods.The state inference problem consists of estimating some latent variable that is not directly observable in the output from the system. The parameter inference problem is concerned with fitting a pre-specified model structure to the observed output from the system. In input design, we are interested in constructing an input to the system, which maximises the information that is available about the parameters in the system output. All of these problems are analytically intractable for nonlinear SSMs. Instead, we make use of SMC to approximate the solution to the state inference problem and to solve the input design problem. Furthermore, we make use of Markov chain Monte Carlo (MCMC) and Bayesian optimisation (BO) to solve the parameter inference problem.In this thesis, we propose new methods for parameter inference in SSMs using both Bayesian and maximum likelihood inference. More specifically, we propose a new proposal for the particle Metropolis-Hastings algorithm, which includes gradient and Hessian information about the target distribution. We demonstrate that the use of this proposal can reduce the length of the burn-in phase and improve the mixing of the Markov chain.Furthermore, we develop a novel parameter inference method based on the combination of BO and SMC. We demonstrate that this method requires a relatively small amount of samples from the analytically intractable likelihood, which are computationally costly to obtain. Therefore, it could be a good alternative to other optimisation based parameter inference methods. The proposed BO and SMC combination is also extended for parameter inference in nonlinear SSMs with intractable likelihoods using approximate Bayesian computations. This method is used for parameter inference in a stochastic volatility model with -stable returns using real-world financial data.Finally, we develop a novel method for input design in nonlinear SSMs which makes use of SMC methods to estimate the expected information matrix. This information is used in combination with graph theory and convex optimisation to estimate optimal inputs with amplitude constraints. We also consider parameter estimation in ARX models with Student-t innovations and unknown model orders. Two different algorithms are used for this inference: reversible Jump Markov chain Monte Carlo and Gibbs sampling with sparseness priors. These methods are used to model real-world EEG data with promising results.
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| 14. |
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| 15. |
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| 16. |
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| 17. |
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| 18. |
- Dahlin, T., et al.
(författare)
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Resistivity-ip characterisation and short term monitoring at filborna waste deposit
- 2012
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Ingår i: 74th European Association of Geoscientists and Engineers Conference and Exhibition 2012 Incorporating SPE EUROPEC 2012 : Responsibly Securing Natural Resources - Responsibly Securing Natural Resources. - 9781629937908 ; , s. 4667-4671
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Konferensbidrag (refereegranskat)abstract
- Buried waste in old landfills is an increasing problem as cities expand and grow into areas with former waste deposits. In order to be able to manage and as far as possible reclaim land in such areas, better tools are needed for mapping and characterisation of buried waste and contaminated land. Other problems associated with landfills are leachate water and methane emissions. In the results presented internal landfill structure was successfully mapped using a combination of resistivity and time-domain IP. Differences in electrical properties can be related to different types of materials, and the groundwater level is outlined. Furthermore the results indicate that leachate water migrates into a former stream under the landfill. Variations in resistivity linked to variation in fluid and gas content were captured by short term monitoring. A rainfall event that occurred during the monitoring period acts as an infiltration test and the changes in resistivity outlines the water migration pattern. The results show the potential of resistivity monitoring for tracing fluid migration in the ground, and also shows patterns that may be due to increasing gas contents in line with previous studies.
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| 19. |
- Edin, Sofia, et al.
(författare)
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The Distribution of Macrophages with a M1 or M2 Phenotype in Relation to Prognosis and the Molecular Characteristics of Colorectal Cancer
- 2012
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Ingår i: PLOS ONE. - : PLoS One. - 1932-6203. ; 7:10, s. e47045-
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Tidskriftsartikel (refereegranskat)abstract
- High macrophage infiltration has been correlated to improved survival in colorectal cancer (CRC). Tumor associated macrophages (TAMs) play complex roles in tumorigenesis since they are believed to hold both tumor preventing (M1 macrophages) and tumor promoting (M2 macrophages) activities. Here we have applied an immunohistochemical approach to determine the degree of infiltrating macrophages with a M1 or M2 phenotype in clinical specimens of CRC in relation to prognosis, both in CRC in general but also in subgroups of CRC defined by microsatellite instability (MSI) screening status and the CpG island methylator phenotype (CIMP). A total of 485 consecutive CRC specimens were stained for nitric oxide synthase 2 (NOS2) (also denoted iNOS) as a marker for the M1 macrophage phenotype and the scavenger receptor CD163 as a marker for the M2 macrophage phenotype. The average infiltration of NOS2 and CD163 expressing macrophages along the invasive tumor front was semi-quantitatively evaluated using a four-graded scale. Two subtypes of macrophages, displaying M1 (NOS2(+)) or M2 (CD163(+)) phenotypes, were recognized. We observed a significant correlation between the amount of NOS2(+) and CD163(+) cells (P<0.0001). A strong inverse correlation to tumor stage was found for both NOS2 (P<0.0001) and CD163 (P<0.0001) infiltration. Furthermore, patients harbouring tumors highly infiltrated by NOS2+ cells had a significantly better prognosis than those infiltrated by few NOS2+ cells, and this was found to be independent of MSI screening status and CIMP status. No significant difference was found on cancer-specific survival in groups of CRC with different NOS2/CD163 ratios. In conclusion, an increased infiltration of macrophages with a M1 phenotype at the tumor front is accompanied by a concomitant increase in macrophages with a M2 phenotype, and in a stage dependent manner correlated to a better prognosis in patients with CRC.
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| 20. |
- Eklöf, Vincy, 1984-, et al.
(författare)
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The prognostic role of KRAS, BRAF, PIK3CA and PTEN in colorectal cancer
- 2013
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Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 108:10, s. 2153-2163
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Tidskriftsartikel (refereegranskat)abstract
- Background Mutations in KRAS, BRAF, PIK3CA and PTEN expression have been in focus to predict the effect of epidermal growth factor receptor-blocking therapy in colorectal cancer (CRC). Here, information on these four aberrations was collected and combined to a Quadruple index and used to evaluate the prognostic role of these factors in CRC. Patients We analysed the mutation status in KRAS, BRAF and PIK3CA and PTEN expression in two separate CRC cohorts, Northern Sweden Health Disease Study (NSHDS; n = 197) and Colorectal Cancer in Umea Study (CRUMS; n = 414). A Quadruple index was created, where Quadruple index positivity specifies cases with any aberration in KRAS, BRAF, PIK3CA or PTEN expression. Results Quadruple index positive tumours had a worse prognosis, significant in the NSHDS but not in the CRUMS cohort (NSHDS; P = 0.003 and CRUMS; P = 0.230) in univariate analyses but significance was lost in multivariate analyses. When analysing each gene separately, only BRAF was of prognostic significance in the NSHDS cohort (multivariate HR 2.00, 95% CI: 1.16-3.43) and KRAS was of prognostic significance in the CRUMS cohort (multivariate HR 1.48, 95% CI: 1.02-2.16). Aberrations in PIK3CA and PTEN did not add significant prognostic information. Conclusions Our results suggest that establishment of molecular subgroups based on KRAS and BRAF mutation status is important and should be considered in future prognostic studies in CRC.
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| 21. |
- Gustafsson, Sofia B, et al.
(författare)
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High tumour cannabinoid CB(1) receptor immunoreactivity negatively impacts disease-specific survival in stage II microsatellite stable colorectal cancer
- 2011
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Ingår i: PLOS ONE. - San Francisco, CA : Public Library of Science. - 1932-6203. ; 6:8, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is good evidence in the literature that the cannabinoid system is disturbed in colorectal cancer. In the present study, we have investigated whether CB(1) receptor immunoreactive intensity (CB(1)IR intensity) is associated with disease severity and outcome. Methodology/Principal Findings: CB(1)IR was assessed in formalin-fixed, paraffin-embedded specimens collected with a consecutive intent during primary tumour surgical resection from a series of cases diagnosed with colorectal cancer. Tumour centre (n = 483) and invasive front (n = 486) CB(1)IR was scored from 0 (absent) to 3 (intense staining) and the data was analysed as a median split i.e. CB(1)IR <2 and >= 2. In microsatellite stable, but not microsatellite instable tumours (as adjudged on the basis of immunohistochemical determination of four mismatch repair proteins), there was a significant positive association of the tumour grade with the CB1IR intensity. The difference between the microsatellite stable and instable tumours for this association of CB(1)IR was related to the CpG island methylation status of the cases. Cox proportional hazards regression analyses indicated a significant contribution of CB(1)IR to disease-specific survival in the microsatellite stable tumours when adjusting for tumour stage. For the cases with stage II microsatellite stable tumours, there was a significant effect of both tumour centre and front CB(1)IR upon disease specific survival. The 5 year probabilities of event-free survival were: 8565 and 66+/-8%; tumour interior, 86+/-4% and 63+/-8% for the CB(1)IR<2 and CB(1)IR >= 2 groups, respectively. Conclusions/Significance: The level of CB(1) receptor expression in colorectal cancer is associated with the tumour grade in a manner dependent upon the degree of CpG hypermethylation. A high CB(1)IR is indicative of a poorer prognosis in stage II microsatellite stable tumour patients.
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| 22. |
- Henriksson, Maria L, et al.
(författare)
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Colorectal Cancer Cells Activate Adjacent Fibroblasts Resulting in FGF1/FGFR3 Signaling and Increased Invasion.
- 2011
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Ingår i: American Journal of Pathology. - : Elsevier. - 0002-9440 .- 1525-2191. ; 178:3, s. 1387-1394
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Tidskriftsartikel (refereegranskat)abstract
- Cancer-associated fibroblasts expressing fibroblast activation protein (FAP) have been implicated in the invasive behavior of colorectal cancer. In this study, we use FAP expression as a marker of fibroblast activation and analyze the effect of activated fibroblasts on colorectal cancer migration and invasion in experimental cell studies. We also investigated the expression pattern of FAP in cancer-associated fibroblasts during transformation from benign to malignant colorectal tumors. In immunohistochemical analyses, FAP was expressed in fibroblasts in all colorectal cancer samples examined, whereas all normal colon, hyperplastic polyps, or adenoma samples were negative. In in vitro studies, conditioned medium from colon cancer cells, but not adenoma cells, activated fibroblasts by inducing FAP expression. These activated fibroblasts increased the migration and invasion of colon cancer cells in Boyden chamber experiments and in a three-dimensional cell culture model. We identify fibroblast growth factor 1/fibroblast growth factor receptor 3 (FGF1/FGFR-3) signaling as mediators leading to the increased migration and invasion. Activated fibroblasts increase their expression of FGF1, and by adding a fibroblast growth factor receptor inhibitor, as well as an FGF1-neutralizing antibody, we reduced the migration of colon cancer cells. Our findings provide evidence of a possible molecular mechanism involved in the cross talk between cancer cells and fibroblasts leading to cancer cell invasion.
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| 23. |
- Ikenoya, Y., et al.
(författare)
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Optical Resonances in Short-Range Ordered Nanoholes in Ultrathin Aluminum/Aluminum Nitride Multilayers
- 2013
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Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 117:12, s. 6373-6382
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Tidskriftsartikel (refereegranskat)abstract
- Nanoholes with short-range ordering were fabricated in ultrathin aluminum/aluminum nitride multilayer films where each layer is as thin as a few nanometers. Optical resonances of the trilayer system with a single metallic layer and five-layer system with two metallic layers were successfully tuned in the visible-near-infrared (vis/NIR) range. The resonance wavelength as well as the width can be predicted and designed by solving the dispersion relation and comparing with the lateral dimension of the short-range ordering. To solve the dispersion relation, we developed a general formulation for multilayer systems. The thermal stability of the fabricated nanoholes in ultrathin multilayers was also tested by vacuum annealing the samples up to 400 degrees C. While no structural change of the nanohole or the multilayer surface has been observed, the optical property showed almost no change in the resonance confirming no structural change but emergence of the interband transition!
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| 24. |
- Isaksson-Mettävainio, Martin, et al.
(författare)
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High SMAD4 levels appear in MSI and hypermethylated colon cancers, and indicate a better prognosis
- 2012
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Ingår i: International Journal of Cancer. - Geneve : International union against cancer. - 0020-7136 .- 1097-0215. ; 131, s. 779-788
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer (CRC) is one of the most common causes of cancer related deaths in western countries. CRC are commonly divided in cancers showing microsatellite stability (MSS) or microsatellite instability (MSI). A more novel classification is dependent on promoter hypermethylation of CpG islands (the CpG island methylator phenotype, CIMP), where cancers show high, low or negative methylation status. SMAD4, located on chromosome 18q, has been thoroughly investigated during the last years. Loss of SMAD4 expression has been reported to correlate with poor CRC patient prognosis. In this study we analyze the impact of SMAD4 expression on prognosis in relation to MSI screening status and CIMP status. 479 paraffin-embedded specimens of CRC were examined for nuclear SMAD4 expression using immunohistochemistry. The tumors were scored loss (-), moderate (+) and high (++) expressing tumors. Loss of SMAD4 correlated significantly with decreased survival in all colon cancer patients. High SMAD4 expression, on the other hand, was significantly associated with increased survival, especially in colon cancer patients which has undergone potential curative surgery. In addition, in MSI tumors and CIMP-high tumors, high SMAD4 expression was significantly related to increase in survival, while loss of SMAD4 resulted in a significantly poorer prognosis. SMAD4 expression was not correlated to prognosis in rectal cancer cases. We conclude, loss of SMAD4 indicates a poor prognosis in colon cancer patients. The novel findings that high SMAD4 expression predicts a better prognosis suggests that SMAD4 immunohistochemistry could constitute a prognostic marker in combination with CIMP and MSI screening status.
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| 25. |
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| 26. |
- Lilja, Hans, et al.
(författare)
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Prediction of Significant Prostate Cancer Diagnosed 20 to 30 Years Later With a Single Measure of Prostate-Specific Antigen at or Before Age 50
- 2011
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Ingår i: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; 117:6, s. 1210-1219
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We previously reported that a single prostate-specific antigen (PSA) measured at ages 44-50 was highly predictive of subsequent prostate cancer diagnosis in an unscreened population. Here we report an additional 7 years of follow-up. This provides replication using an independent data set and allows estimates of the association between early PSA and subsequent advanced cancer (clinical stage >= T3 or metastases at diagnosis). METHODS: Blood was collected from 21,277 men in a Swedish city (74% participation rate) during 1974-1986 at ages 33-50. Through 2006, prostate cancer was diagnosed in 1408 participants; we measured PSA in archived plasma for 1312 of these cases (93%) and for 3728 controls. RESULTS: At a median follow-up of 23 years, baseline PSA was strongly associated with subsequent prostate cancer (area under the curve, 0.72; 95% Cl, 0.70-0.74; for advanced cancer, 0.75; 95% Cl, 0.72-0.78). Associations between PSA and prostate cancer were virtually identical for the initial and replication data sets, with 81% of advanced cases (95% Cl, 77%-86%) found in men with PSA above the median (0.63 ng/mL at ages 44-50). CONCLUSIONS: A single PSA at or before age 50 predicts advanced prostate cancer diagnosed up to 30 years later. Use of early PSA to stratify risk would allow a large group of low-risk men to be screened less often but increase frequency of testing on a more limited number of high-risk men. This is likely to improve the ratio of benefit to harm for screening. Cancer 2011;117:1210-9. (C) 2010 American Cancer Society
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| 27. |
- Loke, M. H., et al.
(författare)
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Methods to reduce banding effects in 3-D resistivity inversion
- 2010
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Ingår i: Near Surface Geoscience 2010. - 9781629937892
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Konferensbidrag (refereegranskat)abstract
- Three-dimensional surveys are required to accurately resolve structures in very complex areas. In many cases the 3-D data set is collated from a series of parallel 2-D survey lines, and frequently the distance between the lines is more than the electrode spacing along the lines. The inversion of such data sets frequently produce models with banded near-surface anomalies that are aligned parallel (or perpendicular) to the lines. It is shown that such banded structures can be caused by the data acquisition geometry. Several modifications to the smoothness-constrained least-squares inversion method are examined to reduce such artifacts in the inversion model. One method is to use a higher damping factor for the model cells in the near-surface layers. The banding effects can also be reduced using a model discretization such that the width and length of the model cells are similar although the spacing between the lines is larger than the in-line electrode spacing. The remaining banding artifacts can be further reduced by modifying the horizontal roughness filter used such that it has components in the diagonal directions as well as in the directions along and perpendicular to the 2-D survey lines.
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| 28. |
- Loke, M. H., et al.
(författare)
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Smoothness-constrained time-lapse inversion of data from 3D resistivity surveys
- 2014
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Ingår i: Near Surface Geophysics. - : Wiley. - 1873-0604 .- 1569-4445. ; 12:1, s. 5-24
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Tidskriftsartikel (refereegranskat)abstract
- Three-dimensional resistivity surveys and their associated inversion models are required to accurately resolve structures exhibiting very complex geology. In the same light, 3D resistivity surveys collected at multiple times are required to resolve temporally varying conditions. In this work we present 3D data sets, both synthetic and real, collected at different times. The large spatio-temporal data sets are then inverted simultaneously using a least-squares methodology that incorporates roughness filters in both the space and time domains. The spatial roughness filter constrains the model resistivity to vary smoothly in the x-, y- and z-directions. A temporal roughness filter is also applied that minimizes changes in the resistivity between successive temporal inversion models and the L-curve method is used to determine the optimum weights for both spatial and temporal roughness filters. We show that the use of the temporal roughness filter can accurately resolve changes in the resistivity even in the presence of noise. The L1- and L2-norm constraints for the temporal roughness filter are first examined using a synthetic model. The synthetic data test shows that the L1-norm temporal constraint produces significantly more accurate results when the resistivity changes abruptly with time. The model obtained with the L1-norm temporal constraint is also less sensitive to random noise compared with independent inversions (i.e., without any temporal constraint) and the L2-norm temporal constraint. Anomalies that are common in models using independent inversions and the L2-norm and L1-norm temporal constraints are likely to be real. In contrast, anomalies present in a model using independent inversions but that are significantly reduced with the L2-norm and L1-norm constraints are likely artefacts. For field data sets, the method successfully recovered temporal changes in the subsurface resistivity from a landfill monitoring survey due to rainwater infiltration, as well as from an experiment to map the migration of sodium cyanide solution from an injection well using surface and borehole electrodes in an area with significant topography.
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| 29. |
- Maripuu, Amanda, et al.
(författare)
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Reconstruction of sciatic nerve after traumatic injury in humans - factors influencing outcome as related to neurobiological knowledge from animal research
- 2012
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Ingår i: Journal of Brachial Plexus and Peripheral Nerve Injury. - : Georg Thieme Verlag KG. - 1749-7221. ; 7:1, s. 40-52
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Forskningsöversikt (refereegranskat)abstract
- Background: The aim was to evaluate what can be learned from rat models when treating patients suffering from a sciatic nerve injury.Methods: Two patients with traumatic sciatic nerve injury are presented with examination of motor and sensory function with a five-year follow-up. Reconstruction of the nerve injury was performed on the second and third day, respectively, after injury using sural nerve grafts taken from the injured leg. The patients were examined during follow-up by electromyography (EMG), MRI and functionalMRI (fMRI) to evaluate nerve reinnervation, cell death in dorsal root ganglia (DRG) and cortical activation; factors that were related to clinical history in the patients.Results: One patient regained good motor function of the lower leg and foot, confirmed by EMG showing good activation in the leg muscles and some reinnervation in the foot muscles, as well as some sensory function of the sole of the foot. The other patient regained no motor (confirmed by EMG) or sensory function in the leg or foot. Factors most influential on outcome in two cases were type of injury, nerve gap length and particularly type of reconstruction. A difference in follow-up and rehabilitation likely also influence outcome. MRI did not show any differences in DRG size of injured side compared to the uninjured side. fMRI showed normal activation in the primary somatosensory cortex as a response to cutaneous stimulation of the normal foot. However, none of the two patients showed any activation in the primary somatosensory cortex following cutaneous stimulation of the injured foot.Conclusions: In decision making of nerve repair and reconstruction data from animal experiments can be translated to clinical practice and to predict outcome in patients, although such data should be interpreted with caution and linked to clinical experience. Rat models may be useful to identify and study factors that influence outcome after peripheral nerve repair and reconstruction; procedures that should be done correctly and with a competent team. However, some factors, such as cognitive capacity and coping, known to influence outcome following nerve repair, are difficult to study in animal models. Future research has to find and develop new paths and techniques to study changes in the central nervous system after nerve injury and develop strategies to utilize brain plasticity during the rehabilitation.
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- Van Guelpen, Bethany, et al.
(författare)
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One-carbon metabolism and CpG island methylator phenotype status in incident colorectal cancer : a nested case-referent study
- 2010
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Ingår i: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 0957-5243 .- 1573-7225. ; 21:4, s. 557-566
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We related prediagnostic plasma folate, vitamin B12, and total homocysteine concentrations, and the MTHFR 677C>T and 1298A>C polymorphisms, to the risk of colorectal cancer with and without the CpG island methylator phenotype (CIMP). METHODS: This was a nested case-referent study of 190 cases and double, matched referents from the large, population-based Northern Sweden Health and Disease Study. Using archival tumor tissue, promoter methylation in an eight-gene panel was analyzed by MethyLight. RESULTS: A reduced risk of CIMP-low/CIMP-high CRC (>/=1 gene methylated) was observed in subjects with very low plasma folate concentrations [multivariate odds ratio 2.96 (95% CI 1.24-7.08) for quintiles two to five versus one (lowest)]. With the exception of a reduced risk in MTHFR 677 TT-homozygotes, none of the other one-carbon variables were associated with the risk of CIMP-low/CIMP-high CRC. For CIMP-negative CRC, only the MTHFR polymorphisms were statistically significantly related to risk, inversely for 677C>T and positively for 1298A>C, but a tendency toward a reduced risk was observed in subjects with an adequate methyl availability, combining the plasma variables [multivariate odds ratio 0.61 (95% CI 0.32-1.15)]. CONCLUSION: Though limited by low power, these findings suggest the possibility of different roles for one-carbon metabolism in different pathways of colorectal tumorigenesis.
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- Wikberg, Maria L., et al.
(författare)
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High intratumoral expression of fibroblast activation protein (FAP) in colon cancer is associated with poorer patient prognosis.
- 2013
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Ingår i: Tumor Biology. - : Springer Netherlands. - 1010-4283 .- 1423-0380. ; 34:2, s. 1013-1020
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Tidskriftsartikel (refereegranskat)abstract
- -An active stroma is important for cancer cell invasion and metastasis. We investigated the expression of fibroblast activation protein (FAP) in relation to patient prognosis in colorectal cancer. Colorectal cancer specimens from 449 patients were immunohistochemically stained with a FAP antibody and evaluated in the tumor center and tumor front using a semiquantitative four-level scale. FAP was expressed by fibroblasts in 85-90 % of the tumors examined. High versus no/low expression in the tumor center was associated with poor prognosis (multivariate hazard ratio, HR = 1.72; 95 % CI 1.07-2.77, p = 0.025). FAP expression in the tumor front, though more frequent than in the tumor center, was not associated with prognosis. FAP expression in the tumor center was more common in specimens with positive microsatellite instability (MSI) screening status and in patients with high CpG island methylator phenotype (CIMP) status. However, inclusion of MSI screening status and CIMP status in the multivariate analysis strengthened the risk estimates for high FAP expression in the tumor center (HR = 1.89; 95 % CI 1.13-3.14; p = 0.014), emphasizing the role of FAP as an independent prognostic factor. Stromal FAP expression is common in colorectal cancer, and we conclude that high FAP expression in the tumor center, but not the tumor front, is an independent negative prognostic factor.
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