| 1. |
- Engström, Gunnar, et al.
(författare)
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The Swedish CArdioPulmonary BioImage Study : objectives and design
- 2015
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 278:6, s. 645-659
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Tidskriftsartikel (refereegranskat)abstract
- Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.
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| 2. |
- Forsling, Robin, 1988-, et al.
(författare)
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Conservative Linear Unbiased Estimation Under Partially Known Covariances
- 2022
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Ingår i: IEEE Transactions on Signal Processing. - : IEEE. - 1053-587X .- 1941-0476. ; 70, s. 3123-3135
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Tidskriftsartikel (refereegranskat)abstract
- Mean square error optimal estimation requires the full correlation structure to be available. Unfortunately, it is not always possible to maintain full knowledge about the correlations. One example is decentralized data fusion where the cross-correlations between estimates are unknown, partly due to information sharing. To avoid underestimating the covariance of an estimate in such situations, conservative estimation is one option. In this paper the conservative linear unbiased estimator is formalized including optimality criteria. Fundamental bounds of the optimal conservative linear unbiased estimator are derived. A main contribution is a general approach for computing the proposed estimator based on robust optimization. Furthermore, it is shown that several existing estimation algorithms are special cases of the optimal conservative linear unbiased estimator. An evaluation verifies the theoretical considerations and shows that the optimization based approach performs better than existing conservative estimation methods in certain cases.
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| 3. |
- Zirakzadeh, A. Ali, et al.
(författare)
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Doxorubicin enhances the capacity of B cells to activate T cells in urothelial urinary bladder cancer
- 2017
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Ingår i: Clinical Immunology. - : Elsevier BV. - 1521-6616 .- 1521-7035. ; 176, s. 63-70
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is currently treated by a combination of therapies, including chemotherapy which is believed to suppress the immune system. Combination of immunotherapy and chemotherapy correlates with improved survival but needs careful planning in order to achieve a synergistic effect. In this study, we have demonstrated that doxorubicin treatment of B cells resulted in increased expression of CD86 and concordantly increased CD4(+) T cell activation in the presence of superantigen, an effect that was inhibited by the addition of a CD86 blocking antibody. Furthermore, doxorubicin resulted in decreased expression of the anti-inflammatory cytokines IL-10 and TNF-alpha. Finally, B cells from urinary bladder cancer patients, treated with a neoadjuvant regiment containing doxorubicin, displayed increased CD86-expression. We conclude that doxorubicin induces CD86 expression on B cells and hence enhances their antigen-presenting ability in vitro, a finding verified in patients. Development of tailored time and dose schedules may increase the effectiveness of combining chemotherapy and immunotherapy.
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| 4. |
- Ahlén Bergman, Emma, et al.
(författare)
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Increased CD4+ T cell lineage commitment determined by CpG methylation correlates with better prognosis in urinary bladder cancer patients
- 2018
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Ingår i: Clinical Epigenetics. - : BMC. - 1868-7083 .- 1868-7075. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Urinary bladder cancer is a common malignancy worldwide. Environmental factors and chronic inflammation are correlated with the disease risk. Diagnosis is performed by transurethral resection of the bladder, and patients with muscle invasive disease preferably proceed to radical cystectomy, with or without neoadjuvant chemotherapy. The anti-tumour immune responses, known to be initiated in the tumour and draining lymph nodes, may play a major role in future treatment strategies. Thus, increasing the knowledge of tumour-associated immunological processes is important. Activated CD4+ T cells differentiate into four main separate lineages: Th1, Th2, Th17 and Treg, and they are recognized by their effector molecules IFN-γ, IL-13, IL-17A, and the transcription factor Foxp3, respectively. We have previously demonstrated signature CpG sites predictive for lineage commitment of these four major CD4+ T cell lineages. Here, we investigate the lineage commitment specifically in tumour, lymph nodes and blood and relate them to the disease stage and response to neoadjuvant chemotherapy.RESULTS: Blood, tumour and regional lymph nodes were obtained from patients at time of transurethral resection of the bladder and at radical cystectomy. Tumour-infiltrating CD4+ lymphocytes were significantly hypomethylated in all four investigated lineage loci compared to CD4+ lymphocytes in lymph nodes and blood (lymph nodes vs tumour-infiltrating lymphocytes: IFNG -4229 bp p < 0.0001, IL13 -11 bp p < 0.05, IL17A -122 bp p < 0.01 and FOXP3 -77 bp p > 0.05). Examination of individual lymph nodes displayed different methylation signatures, suggesting possible correlation with future survival. More advanced post-cystectomy tumour stages correlated significantly with increased methylation at the IFNG -4229 bp locus. Patients with complete response to neoadjuvant chemotherapy displayed significant hypomethylation in CD4+ T cells for all four investigated loci, most prominently in IFNG p < 0.0001. Neoadjuvant chemotherapy seemed to result in a relocation of Th1-committed CD4+ T cells from blood, presumably to the tumour, indicated by shifts in the methylation patterns, whereas no such shifts were seen for lineages corresponding to IL13, IL17A and FOXP3.CONCLUSION: Increased lineage commitment in CD4+ T cells, as determined by demethylation in predictive CpG sites, is associated with lower post-cystectomy tumour stage, complete response to neoadjuvant chemotherapy and overall better outcome, suggesting epigenetic profiling of CD4+ T cell lineages as a useful readout for clinical staging.
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| 5. |
- Arehag, Marie, 1952, et al.
(författare)
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Outcomes-focused evaluation of engineering programs - Inhibitor or stimulant for improvement?
- 2013
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Ingår i: Proceedings of the 9th International CDIO Conference, Cambridge, USA.
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Konferensbidrag (refereegranskat)abstract
- In Sweden, a new model for quality evaluation of higher education is being introduced. It is internationally unique. A very strong emphasis on assessing the quality of an entire education through its outcomes, defined by samples of final degree reports, is perhaps the most original feature of the model. This is claimed to enable a direct assessment of quality rather than the indirect assessment used in conventional models. The model has, however, been intensively debated during its development and first years of use. The aims of this paper are first to evaluate in what ways and to what extent the Swedish national model for evaluation of higher education contributes to the quality improvement of the evaluated programs, and second to describe and evaluate an approach for organizing the project to prepare the evaluation documentation for a large-scale education evaluation. The paper concludes that on an overall and averaged level, the project participants estimated that the model will contribute to positive effects. Specific areas are identified including ethics and focus of final degree reports. However, there is a strong variance in the data: There is a substantial fraction of participants who have not identified any improvements or weak spots, and who do not think that the evaluation preparation will positively affect education quality development. Chalmers University of Technology chose to approach the evaluation with a centrally managed project. The setup gave possibilities for rationalization through common training, supporting materials, a common document database and for information sharing across departmental boundaries. Nevertheless, the project was very time-consuming with an average of 540 hours spent for each program/degree.
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| 6. |
- Balachandramurthi, Arun Ramanathan, 1989-, et al.
(författare)
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Anisotropic fatigue properties of Alloy 718 manufactured by Electron Beam Powder Bed Fusion
- 2020
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Ingår i: International Journal of Fatigue. - : Elsevier. - 0142-1123 .- 1879-3452. ; 141
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Tidskriftsartikel (refereegranskat)abstract
- In this study, Alloy 718 specimens manufactured by Electron Beam Powder Bed Fusion process are subjected to two different post-treatments to have different microstructural features. Low cycle fatigue testing has been performed both parallel and transverse to the build direction. EB-PBF Alloy 718 exhibits anisotropic fatigue behaviour; the fatigue life is better along the parallel direction compared to the transverse direction. The anisotropy in fatigue life is related to the anisotropy in the Young’s modulus. The pseudo-elastic stress vs. fatigue life approach is presented as a potential solution to handle anisotropy in fatigue life assessment of additively manufactured engineering components. © 2020 The Authors
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| 7. |
- Balachandramurthi, Arun Ramanathan, 1989-, et al.
(författare)
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On the microstructure of laser beam powder bed fusion alloy 718 and its influence on the low cycle fatigue behaviour
- 2020
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Ingår i: Materials. - : MDPI AG. - 1996-1944 .- 1996-1944. ; 13:22
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Tidskriftsartikel (refereegranskat)abstract
- Additive manufacturing of Alloy 718 has become a popular subject of research in recent years. Understanding the process-microstructure-property relationship of additively manufactured Alloy 718 is crucial for maturing the technology to manufacture critical components. Fatigue behaviour is a key mechanical property that is required in applications such as gas turbines. Therefore, in the present work, low cycle fatigue behaviour of Alloy 718 manufactured by laser beam powder bed fusion process has been investigated. The material was tested in as-built condition as well as after two different thermal post-treatments. Three orientations with respect to the building direction were tested to evaluate the anisotropy. Testing was performed at room temperature under controlled amplitudes of strain. It was found that defects, inclusions, strengthening precipitates, and Young’s modulus influence the fatigue behaviour under strain-controlled conditions. The strengthening precipitates affected the deformation mechanism as well as the cycle-dependent hardening/softening behaviour. The defects and the inclusions had a detrimental effect on fatigue life. The presence of Laves phase in LB-PBF Alloy 718 did not have a detrimental effect on fatigue life. Young’s modulus was anisotropic and it contributed to the anisotropy in strain-life relationship. Pseudo-elastic stress vs. fatigue life approach could be used to handle the modulus-induced anisotropy in the strain-life relationship. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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| 8. |
- Hansson, Johan, 1964-
(författare)
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Loco-regional Treatment of Peritoneal Carcinomatosis: Survival, Morbidity and Quality of Life
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Peritoneal carcinomatosis (PC) is traditionally regarded as a terminal stage of disease with a poor prognosis and systemic chemotherapy is regarded as palliative treatment. In order to improve survival and even to achieve cure for selected patients with PC, cytoreductive surgery and intraperitoneal che-motherapy have been advocated. Despite complete macroscopic removal of tumour, residual microscopic malignant cells might result in recurrence. Intraperitoneal chemotherapy aims to kill residual malignant cells and thereby needs to be distributed in the entire peritoneal cavity. This aggres-sive combined loco-regional treatment has a high risk of morbidity and mor-tality. Whether the increased risks are acceptable to improve survival re-quires investigation and the impact of loco-regional treatment of PC on health-related quality of life (HRQL) needs to bee explored The overall aim of this thesis was to analyse the impact of cytoreductive surgery and intraperitoneal chemotherapy on patients with peritoneal carci-nomatosis. A significant survival improvement (median 32 months) was seen in 18 patients with PC of colorectal origin subjected to loco-regional treatment, in comparison to matched controls treated with systemic chemotherapy (me-dian survival 14 months, Paper I). The results of single-photon emission computer-tomography (SPECT) in 51 patients were correlated to the number of intraperitoneal chemotherapy courses that could be performed without further surgery (Paper II). Postoperative 30-days morbidity and 90-days mortality was investigated in 123 PC-patients after loco-regional treatment. Severe adverse events occurred in 51 (41%) patients. Five patients (4%) had treatment-related mortality. Stoma formation, duration of surgery, periopera-tive blood loss, and extent of PC was associated with morbidity (Paper III). HRQL was investigated in 64 patients. HRQL was negatively affected at 3 months but a partial recovery was seen at 8 months. 30-day morbidity did not have any impact on HRQL at 8 months (Paper IV). This treatment there fore appears justified despite considerable toxicity in view of possible life prolongation.
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| 9. |
- Hansson, Johan, 1964-, et al.
(författare)
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Quality of life in peritoneal carcinomatosis after cytoreductive surgery and intraperitoneal chemotherapy
- 2012
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Tidskriftsartikel (refereegranskat)abstract
- Background:Cytoreductive surgery (CRS) plus intraperitoneal chemotherapy (IPC) is considered the most optimal treatment for peritoneal carcinomatosis (PC). Health-related quality of life (HRQL) after treatment is largely unknown. The aims were to assess HRQL in patients with PC treated with CRS and IPC and to analyse the influence of clinical variables on HRQL.Methods:HRQL was assessed prospectively between November 2001 and March 2005 in 64 consecutive patients with PC through two different self-administered instruments, EORTC QLQ-C30 v3.0 (QLQ-C30) and the SF-36 Health Survey (SF-36), preoperatively, and after 3 and 8 months. Results:For QLQ-C30, 44 (69%) and for SF-36, 42 (66%) out of 64 patients had a complete follow-up. Most scales were worsened at baseline compared to reference in both instruments. HRQL was reduced at 3-months in QLQ-C30 (physical, role and emotional functioning) and in SF-36 (physical summary score). At 8-months, all scales returned to baseline in QLQ-C30, except physical functioning which was still reduced and dyspnoea that was worsened. In SF-36, all values returned to baseline levels. At 8-months, presence of a stoma worsened social functioning and a high peritoneal cancer index decreased social functioning and global QoL, the use of hyperthermic intraperitoneal chemotherapy and 30-days postoperative morbidity had no impact on HRQL. Conclusion: CRS with IPC results in reasonable short-term HRQL despite high initial morbidity and an initial decrease in HRQL parameters. The study adds to the notion that this treatment appears beneficial in light of probable life prolongation, despite considerable toxicity.
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| 10. |
- Hansson, Johan, 1964-, et al.
(författare)
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Single-photon emission computed tomography for prediction of treatment results in sequential intraperitoneal chemotherapy at peritoneal carcinomatosis
- 2012
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Ingår i: Annals of Surgery. - 0003-4932 .- 1528-1140.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cytoreductive surgery and intraperitoneal chemotherapy (IPC) treatment can improve survival in peritoneal carcinomatosis. One of the reasons for failure of sequential postoperative intraperitoneal chemotherapy (SPIC) is lack of distribution of the chemotherapy in the peritoneal cavity. The primary aim of this study was to evaluate single-photon emission computed tomography (SPECT) as a predictor of successful SPIC treatment and prognosis. A secondary aim was to assess the relationship between SPECT, feasibility of SPIC, and clinical variables.Methods: Fifty-one patients (mean age 52 years, range 14-74, 20 women) were treated with Cytoreductive surgery and SPIC. SPECT studies with intraperitoneal (i.p.) Technetium-99 via a Port-a-Cath (PaC) were performed before the second course of treatment. The i.p. distribution was registered as a detected volume (DV) at four different threshold settings (1, 2, 5, and 10%) of the global maximum intensity of the SPECT examination. A calculation model for SPECT and clinical variables was tested.Results: The DV measured in the SPECT examination predicted the number of subsequent SPIC courses. The highest correlation (R=0.45) for DV was in the 2% threshold setting. Patients with a DV2% lower than mean reached two SPIC courses and patients with a DV2% higher than mean reached six SPIC course. Height correlated to higher DV and a higher number of SPIC courses. Patients with a height lower than mean reached a DV2% at 3930 ml and patients higher than mean reached a DV2% at 5507 ml. A taller person could tolerate more SPIC courses (R=0.28) and patients with a height higher than mean reached six SPIC courses; patients with a height lower than mean reached four courses. There was no correlation between DV and survival.Conclusion: The feasibility of performing SPIC without further surgical intervention can be predicted by SPECT, and it might therefore be an instrument to select which patients should preferably be treated with alternative therapy.
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