| 31. |
- Dimberg, Lina Y., et al.
(author)
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Stat1 activation attenuates IL-6 induced Stat3 activity but does not alter apoptosis sensitivity in multiple myeloma
- 2012
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In: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 12, s. 318-
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Journal article (peer-reviewed)abstract
- Background: Multiple myeloma (MM) is at present an incurable malignancy, characterized by apoptosis-resistant tumor cells. Interferon (IFN) treatment sensitizes MM cells to Fas-induced apoptosis and is associated with an increased activation of Signal transducer and activator of transcription (Stat)1. The role of Stat1 in MM has not been elucidated, but Stat1 has in several studies been ascribed a pro-apoptotic role. Conversely, IL-6 induction of Stat3 is known to confer resistance to apoptosis in MM. Methods: To delineate the role of Stat1 in IFN mediated sensitization to apoptosis, sub-lines of the U-266-1970 MM cell line with a stable expression of the active mutant Stat1C were utilized. The influence of Stat1C constitutive transcriptional activation on endogenous Stat3 expression and activation, and the expression of apoptosis-related genes were analyzed. To determine whether Stat1 alone would be an important determinant in sensitizing MM cells to apoptosis, the U-266-1970-Stat1C cell line and control cells were exposed to high throughput compound screening (HTS). Results: To explore the role of Stat1 in IFN mediated apoptosis sensitization of MM, we established sublines of the MM cell line U-266-1970 constitutively expressing the active mutant Stat1C. We found that constitutive nuclear localization and transcriptional activity of Stat1 was associated with an attenuation of IL-6-induced Stat3 activation and up-regulation of mRNA for the pro-apoptotic Bcl-2 protein family genes Harakiri, the short form of Mcl-1 and Noxa. However, Stat1 activation alone was not sufficient to sensitize cells to Fas-induced apoptosis. In a screening of > 3000 compounds including bortezomib, dexamethasone, etoposide, suberoylanilide hydroxamic acid (SAHA), geldanamycin (17-AAG), doxorubicin and thalidomide, we found that the drug response and IC50 in cells constitutively expressing active Stat1 was mainly unaltered. Conclusion: We conclude that Stat1 alters IL-6 induced Stat3 activity and the expression of pro-apoptotic genes. However, this shift alone is not sufficient to alter apoptosis sensitivity in MM cells, suggesting that Stat1 independent pathways are operative in IFN mediated apoptosis sensitization.
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| 32. |
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| 33. |
- Eriksson, Henrik, 1973, et al.
(author)
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Effects of In-Company Quality Awards on Organizational Performance
- 2003
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In: Total quality management (Print). - : Informa UK Limited. - 0954-4127 .- 1360-0613. ; 14:2, s. 235-242
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Journal article (peer-reviewed)abstract
- The relationship between total quality management (TQM) practices and improved performance has been frequently discussed in the literature. In this paper, the costs and the effects of in-company quality awards on performance are discussed and analysed. The paper covers a survey of Swedish companies that use or have used in-company quality awards to stimulate TQM efforts and thereby to improve performance. The study cannot show any strong evidence of improved performance for units that applied for the in-company quality award. However, in contrast to units that have not applied, some units that have applied for the in-company quality award considered that the results related to performance have improved greatly. One large positive effect perceived by the participating units was increased customer orientation while the largest costs were put on the description of activities and the improvement work itself.
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| 34. |
- Felsberg, Michael, 1974-, et al.
(author)
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Online Learning of Correspondences between Images
- 2013
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In: IEEE Transactions on Pattern Analysis and Machine Intelligence. - : IEEE Computer Society. - 0162-8828 .- 1939-3539. ; 35:1, s. 118-129
-
Journal article (peer-reviewed)abstract
- We propose a novel method for iterative learning of point correspondences between image sequences. Points moving on surfaces in 3D space are projected into two images. Given a point in either view, the considered problem is to determine the corresponding location in the other view. The geometry and distortions of the projections are unknown as is the shape of the surface. Given several pairs of point-sets but no access to the 3D scene, correspondence mappings can be found by excessive global optimization or by the fundamental matrix if a perspective projective model is assumed. However, an iterative solution on sequences of point-set pairs with general imaging geometry is preferable. We derive such a method that optimizes the mapping based on Neyman's chi-square divergence between the densities representing the uncertainties of the estimated and the actual locations. The densities are represented as channel vectors computed with a basis function approach. The mapping between these vectors is updated with each new pair of images such that fast convergence and high accuracy are achieved. The resulting algorithm runs in real-time and is superior to state-of-the-art methods in terms of convergence and accuracy in a number of experiments.
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| 35. |
- Fossa, Sophie D., et al.
(author)
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Ten-and 15-year prostate cancer-specific survival in patients with nonmetastatic high-risk prostate cancer randomized to lifelong hormone treatment alone or combined with radiotherapy (SPCG VII)
- 2014
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In: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 32:4
-
Journal article (other academic/artistic)abstract
- Background: After a median observation time of 7.6 years, Scandinavian Prostate Cancer Group VII randomized trial showed a significant 12% reduction of prostate cancer-specific mortality in patients with locally advanced or histologically aggressive prostate cancer who received three months of total androgen blockade followed by radiotherapy and continuous antiandrogen therapy compared to patients with hormonal treatment only (Widmark et al :Lancet [2009]; 373,1174). Here we provide the 10 (15)-year survival results after a median observation time of 10.7 years. Methods: Between February 1996 and December 2002, 875 patients with locally advanced prostate cancer were randomized (Randomization ratio 1:1). Primary endpoint was prostate cancer-specific survival analyzed by intention to treat. This updated analysis is based on death registry data of the Norwegian patients (2/3 of the population), and on data recorded in CRF database available for the Swedish patients. A Swedish death registry analysis is underway, and will be included in the final analysis at the meeting. Results: Prostate cancer death occurred in 118 out of 439 of the antiandrogen treatment group and in 45 out of 436 men in the combination treatment group (p< 0.0001), with death due to any cause in 210 out of 439 and 161 out of 436 men (p=0.0006), respectively. The 10 (15) year cumulative prostate cancer-specific mortality was more than halved after combined treatment: 18.9% (30.7%) and 8.3% (12.4%) (HR=0.35;[p<4.1E-10 for 15 year results]), and overall mortality was 35.3% (56.7%) and 26.4% (43.4%) (HR=0.70; P=0.0006 for 15 year results), respectively. Conclusions: Addition of local radiotherapy to hormonal treatment in patients with non-metastatic locally advanced or high-risk prostate cancer more than halved the 10 and 15 year prostate cancer-specific mortality and substantially decreased overall mortality.
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| 36. |
- Fossa, Sophie D., et al.
(author)
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Ten- and 15-yr Prostate Cancer-specific Mortality in Patients with Nonmetastatic Locally Advanced or Aggressive Intermediate Prostate Cancer, Randomized to Lifelong Endocrine Treatment Alone or Combined with Radiotherapy : Final Results of The Scandinavian Prostate Cancer Group-7
- 2016
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In: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 70:4, s. 684-691
-
Journal article (peer-reviewed)abstract
- Background: In high-risk prostate cancer (PCa), no study with observation times beyond 10 yr has demonstrated survival improvement after addition of prostatic radiotherapy (RAD) to endocrine treatment (ET) alone. Objective: To compare mortality rates in patients receiving ET alone versus ET + RAD. Design, settings, and participants: From 1996 to 2002, 875 Scandinavian patients with high-risk (90%) or intermediate PCa were randomized to ET or ET + RAD (The Scandinavian Prostate Cancer Group-7). After 3 mo with total androgen blockade in all patients, all individuals continued lifelong antiandrogen monotherapy. Those randomized to ET + RAD started prostate radiotherapy (70 Gy) at 3 mo. Outcome, measurements and statistical analysis: PCa-specific 15-yr mortality represented the primary endpoint. Assessment of the combination treatment effect and prognostic factors was performed in competing risk analyses and Cox proportional-hazard models. Intervention: RAD added to ET. Results and limitations: With a median observation time of 12 yr, the 15-yr PCa-specific mortality rates were 34% (95% confidence interval, 29-39%) and 17% (95% confidence interval, 13-22%) in the ET and ET + RAD arms respectively (p < 0.001). Compared with the ET arm, the median overall survival in the ET + RAD arm was prolonged by 2.4 yr. Treatment with ET alone, age >= 65 yr and increasing histology grade independently increased the risk of PCa-specific and overall mortality. Limitations include nonformal evaluation of comorbidity, the inability to calculate progression-free survival, and lack of information about salvage therapy and toxicity. Conclusions: In patients with nonmetastatic locally advanced or aggressive PCa, ET + RAD reduces the absolute risk of PCa-specific death by 17% at 15 yr compared with ET alone; the comparable 15-yr PCa-specific mortality rates being 17% and 34%. The results warrant a phase 3 study comparing ET + RAD with radical prostatectomy in high-risk PCa. Patient summary: Adding prostatic therapy to lifelong antiandrogen therapy halves the absolute risk of death from prostate cancer from 34% to 17% 15 yr after diagnosis.
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| 37. |
- Fransson, Per, et al.
(author)
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Quality of life in patients with locally advanced prostate cancer given endocrine treatment with or without radiotherapy: 4-year follow-up of SPCG-7/SFUO-3, an open-label, randomised, phase III trial.
- 2009
-
In: The lancet oncology. - : Elsevier. - 1474-5488 .- 1470-2045. ; 10:4, s. 370-80
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Androgen treatment for prostate cancer can adversely affect functional domains of quality of life. We aimed to assess quality of life in men with locally advanced prostate cancer in an open-label phase III randomised comparison between lifelong endocrine treatment with and without radiotherapy. METHODS: We obtained quality-of-life information from 872 (99%) of 875 eligible men with locally advanced prostate cancer (T3; 78%) who were randomly assigned, between 1996 and 2002, to 3 months of total androgen blockade followed by continuous endocrine treatment (439 patients) or the same hormonal treatment with radiotherapy 3 months after randomisation (436 patients). Prospective outcomes included patient-reported symptoms and quality of life assessed with questionnaires from baseline to 4 years after randomisation. Analysis was by intention to treat. This study is registered as an international standard randomised controlled trial, number ISRCTN01534787. FINDINGS: 438 of 439 men assigned endocrine treatment and 434 of 436 assigned endocrine plus radiotherapy completed at least one questionnaire. Missing data at baseline and during follow-up was equally distributed between groups. At 4 years, 64 (18%) of 353 patients on combined therapy and 39 (12%) of 337 on endocrine-alone therapy had moderate to severe urinary bother (p=0.005), and 16 (4%) of 355 on combined therapy and five (2%) of 338 on endocrine treatment alone had pain while urinating (p=0.024). 37 (11%) of 350 in the combined group and 23 (7%) of 35 in the endocrine-only group had overall bother from all bowel symptoms (p=0.022). 281 (85%) of 332 in the combined-treatment group and 227 (72%) of 313 in the endocrine-only group had erectile dysfunction (p=0.0002). Quality of life at 4 years was similar, with the exception of decreased social function in patients receiving endocrine treatment plus radiotherapy. INTERPRETATION: Although addition of radiotherapy to endocrine treatment significantly increased some treatment-related symptoms, none were serious. Given the substantial survival benefit of combined treatment, the increase of symptoms seems acceptable and has little extra effect on quality of life after 4 years compared with endocrine treatment alone.
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| 38. |
- Gerth, Julia, et al.
(author)
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Adhesion phenomena in the secondary shear zone in turning of austenitic stainless steel and carbon steel
- 2014
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In: Journal of Materials Processing Technology. - : Elsevier BV. - 0924-0136 .- 1873-4774. ; 214:8, s. 1467-1481
-
Journal article (peer-reviewed)abstract
- This paper aims to increase the understanding of the adhesion between chip and tool rake face by studying the initial material transfer to the tool during orthogonal machining at 150 m/min. Two types of work material were tested, an austenitic stainless steel, 316L, and a carbon steel, UHB 11. The tools used were cemented carbide inserts coated with hard ceramic coatings. Two different CVD coatings, TiN and Al2O3, produced with two different surface roughnesses, polished and rough, were tested. The influences of both tool surface topography and chemistry on the adhesion phenomena in the secondary shear zone were thus evaluated. Extensive surface analyses of the inserts after cutting were made using techniques such as Scanning Electron Microscopy (SEM), Energy Dispersive Spectroscopy (EDS), X-ray Photoelectron Spectroscopy (XPS), and Transmission Electron Microscopy (TEM). As expected, cutting in the stainless steel resulted in a higher amount of adhered material, compared to cutting in the carbon steel. Remnants of built-up layers were found on the surfaces of the 316L chips but not on the UHB 11 chips. Moreover, it was shown that for both materials the tool roughness had a profound effect, with the rougher surfaces comprising much higher amounts of adhered material than the polished ones. Non-metallic inclusions from both types of workpiece steels accumulate in the high temperature area on the inserts. The general tendency was that higher amounts of transferred material were found on the TiN coating than on the Al2O3 coating after cutting.
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| 39. |
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| 40. |
- Grip, Helena, et al.
(author)
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Classification of Neck Movement Patterns Related to Whiplash-Associated Disorders Using Neural Networks
- 2003
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In: IEEE transactions on information technology in biomedicine. - : IEEE. - 1089-7771 .- 1558-0032. ; 7:4, s. 412-418
-
Journal article (peer-reviewed)abstract
- This paper presents a new method for classification of neck movement patterns related to Whiplash-associated disorders (WAD) using a resilient backpropagation neural network (BPNN). WAD are a common diagnosis after neck trauma, typically caused by rear-end car accidents. Since physical injuries seldom are found with present imaging techniques, the diagnosis can be difficult to make. The active range of the neck is often visually inspected in patients with neck pain, but this is a subjective measure, and a more objective decision support system, that gives a reliable and more detailed analysis of neck movement pattern, is needed. The objective of this study was to evaluate the predictive ability of a BPNN, using neck movement variables as input. Three-dimensional (3-D) neck movement data from 59 subjects with WAD and 56 control subjects were collected with a ProReflex system. Rotation angle and angle velocity were calculated using the instantaneous helical axis method and motion variables were extracted. A principal component analysis was performed in order to reduce data and improve the BPNN performance. BPNNs with six hidden nodes had a predictivity of 0.89, a sensitivity of 0.90 and a specificity of 0.88, which are very promising results. This shows that neck movement analysis combined with a neural network could build the basis of a decision support system for classifying suspected WAD, even though further evaluation of the method is needed.
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