| 1. |
- Jernås, Margareta, 1961, et al.
(författare)
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MS risk genes are transcriptionally regulated in CSF leukocytes at relapse
- 2013
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 19:4, s. 403-410
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Infiltrating T-helper cells, cytotoxic T-cells, B-cells and monocytes are thought to mediate the damage to myelin, oligodendrocytes and axons in multiple sclerosis (MS), which results in progressive disability. OBJECTIVE: The objective of this paper is to explore gene expression profiles of leukocytes in the cerebrospinal fluid (CSF) compartment of MS patients during relapse. METHODS: Global gene expression was analyzed by DNA microarray analysis of cells in CSF from MS patients and controls, and verifications were performed with real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). RESULTS: Fifty percent of the recently described risk genes for MS and 28% of non-risk genes were differently expressed in MS patients compared to controls (χ(2)-test, p=7.7 × 10(-5)). Genes involved in T- and NK-cell processes were up-regulated, and genes involved in processes targeting innate immunity or B-cells were down-regulated in MS. Increased expression of EDN1 and CXCL11 and decreased expression of HMOX1 was verified with real-time PCR and increased expression of CXCL13 was verified with ELISA in CSF. CONCLUSION: DNA microarray analysis is useful in identifying differently expressed genes in CSF leukocytes, which may be important in MS in vivo. Our findings suggest that many of the risk genes for MS are differently expressed in the disease-mediating leukocytes that penetrate the blood-brain barrier.
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| 2. |
- Larsson, Torbjörn, et al.
(författare)
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Convergent Lagrangian heuristics for nonlinear minimum cost network flows
- 2008
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Ingår i: European Journal of Operational Research. - : Elsevier BV. - 0377-2217 .- 1872-6860. ; 189:2, s. 324-346
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Tidskriftsartikel (refereegranskat)abstract
- We consider the separable nonlinear and strictly convex single-commodity network flow problem (SSCNFP). We develop a computational scheme for generating a primal feasible solution from any Lagrangian dual vector, this is referred to as "early primal recovery". It is motivated by the desire to obtain a primal feasible vector before convergence of a Lagrangian scheme, such a vector is not available from a Lagrangian dual vector unless it is optimal. The scheme is constructed such that if we apply it from a sequence of Lagrangian dual vectors that converge to an optimal one, then the resulting primal (feasible) vectors converge to the unique optimal primal flow vector. It is therefore also a convergent Lagrangian heuristic, akin to those primarily devised within the field of combinatorial optimization but with the contrasting and striking advantage that it is guaranteed to yield a primal optimal solution in the limit. Thereby we also gain access to a new stopping criterion for any Lagrangian dual algorithm for the problem, which is of interest in particular if the SSCNFP arises as a subproblem in a more complex model. We construct instances of convergent Lagrangian heuristics that are based on graph searches within the residual graph, and therefore are efficiently implementable, in particular we consider two shortest path based heuristics that are based on the optimality conditions of the original problem. Numerical experiments report on the relative efficiency and accuracy of the various schemes. © 2007 Elsevier B.V. All rights reserved.
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| 3. |
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| 4. |
- Olsson, Caroline, 1970
(författare)
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Predicting Normal Tissue Complications after External Beam Radiation Therapy
- 2010
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Although modern external beam radiation (EBRT) therapy has the ability to conform the dose tightly around the volume to be treated, unwanted irradiation to surrounding normal tissue is still a problem. The probability of a side effect arising in normal tissue after EBRT is commonly modelled by an s-shaped dose-volume response curve where dose or volume are plotted against response (i.e. the frequency with which the side effect occurs). The models are based on sigmoid mathematical functions and are fitted to input data representing the outcome (absence or presence of the studied symptom associated with the side effect) and the dose distribution for potentially injured organs using statistical methods. The purpose of this thesis is to give an overview of the current forms of outcome and dose data, how they are generated and used to model side effects today, some of their limitations, and potential future directions. The results are based on concepts from the literature as well as from the three appended papers. The first two present questionnaire-collected outcome data and 2D dose-volume histogram data of the pubic bone for 650 long-term gynecological cancer survivors treated with pelvic radiation therapy between 1991 and 2003 where one in every ten women reported pubic bone pain. The mean dose to the pubic bone proved critical for pain occurrence and the risk to experience pubic bone pain two or more years after pelvic radiation therapy is expected to be 5 % for a mean absorbed dose of 25 Gy. The third paper presents dose differences between non-corrected and fractionation-corrected combined doses in sequential two-phase treatments using 16 combined dose distributions over a model organ at risk (OAR) “irradiated” with a conventional fractionation schedule (2 Gy per fraction; 46 Gy + 22 Gy). Dose differences up to 6 Gy (50 % of a reference total dose
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| 5. |
- Olsson, Caroline, 1970
(författare)
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Radiation Oncology Data and Modelling Side Effects after Radiation Therapy
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Although modern radiation therapy techniques have the ability to conform the dose distribution of ionizing radiation tightly around the volume to be treated, unwanted irradiation to surrounding organs remains a problem. The probability of a side effect arising in the normal tissue of a patient after radiation therapy can be modelled by sigmoid mathematical functions known as normal tissue complication probability (NTCP) models. Using statistical methods, these are fitted to input data representing the absence or presence of a studied symptom associated with the side effect in question and the dose distribution for potentially injured organs. NTCP models are increasingly being used in the clinic both for treatment evaluation and to guide optimization algorithms for inverse treatment planning although their predictions are associated with uncertainties to varying degrees. The purpose of this thesis is to investigate how different means to represent dose and ways to grade side effects contribute to uncertainties in radiation therapy side effect modelling. Using concepts from the literature and results from two recent Swedish studies including data on parotid gland complications in head and neck cancer patients and pubic bone pain in gynaecological cancer patients, respectively, current generations and representations of dose and side effect data and how these are used in modelling side effects are surveyed. Using similarities and differences in the data by the literature and these two studies, it is concluded that dose data for modelling purposes today is described by dose-volume histograms but can be made more detailed using a three-dimensional format like the structure-specific dose matrix as introduced in this thesis with additional information on dose representation. Side effect data are described by different scales to grade the same or similar symptoms, but also need to include information on factors which may influence modelling results such as effect-modifying factors as well as baseline symptom frequencies in non-irradiated individuals. Altogether, 15 items that capture the essential information needed for radiation therapy side effect modelling are identified, and the outlook for data integration and interoperability in radiation oncology would be improved by using these to form a semantic basis for this domain.
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| 6. |
- Olsson, Caroline, 1970, et al.
(författare)
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Standardizing radiation oncology data for future modelling of side effects after radiation therapy
- 2011
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Ingår i: 1st International Workshop on Managing Interoperability and compleXity in Health Systems, MIXHS'11, Collocated with the 20th ACM International Conference on Information and Knowledge Management, CIKM 2011 Glasgow 28 October 2011 through 28 October 2011. - New York, NY, USA : ACM. - 9781450309547 ; oct 28, s. 67-70
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Konferensbidrag (refereegranskat)abstract
- Wider acceptance of data standards in radiation oncology would facilitate pooling of data from different studies. In turn, this would help clinicians and medical physicists to better understand the relationships between radiation treatments and consequent late developing side effects, and to design treatment plans that improve patients' quality of life. In this paper, we describe challenges of collecting and integrating radiation oncology data from medical records and treatment planning systems for the purpose of modelling side effects after radiation therapy. © 2011 ACM.
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| 7. |
- Waldenström, Ann-Charlotte, 1950, et al.
(författare)
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Pain and mean absorbed dose to the pubic bone after radiotherapy among gynecological cancer survivors.
- 2011
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Ingår i: International journal of radiation oncology, biology, physics. - : Elsevier. - 1879-355X .- 0360-3016. ; 80:4, s. 1171-1180
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To analyze the relationship between mean absorbed dose to the pubic bone after pelvic radiotherapy for gynecological cancer and occurrence of pubic bone pain among long-term survivors.METHODS AND MATERIALS: In an unselected, population-based study, we identified 823 long-term gynecological cancer survivors treated with pelvic radiotherapy during 1991-2003. For comparison, we used a non-radiation-treated control population of 478 matched women from the Swedish Population Register. Pain, intensity of pain, and functional impairment due to pain in the pubic bone were assessed with a study-specific postal questionnaire.RESULTS: We analyzed data from 650 survivors (participation rate 79%) with median follow-up of 6.3 years (range, 2.3-15.0 years) along with 344 control women (participation rate, 72 %). Ten percent of the survivors were treated with radiotherapy; ninety percent with surgery plus radiotherapy. Brachytherapy was added in 81%. Complete treatment records were recovered for 538/650 survivors, with dose distribution data including dose-volume histograms over the pubic bone. Pubic bone pain was reported by 73 survivors (11%); 59/517 (11%) had been exposed to mean absorbed external beam doses <52.5 Gy to the pubic bone and 5/12 (42%) to mean absorbed external beam doses ≥ 52.5 Gy. Thirty-three survivors reported pain affecting sleep, a 13-fold increased prevalence compared with control women. Forty-nine survivors reported functional impairment measured as pain walking indoors, a 10-fold increased prevalence.CONCLUSIONS: Mean absorbed external beam dose above 52.5 Gy to the pubic bone increases the occurrence of pain in the pubic bone and may affect daily life of long-term survivors treated with radiotherapy for gynecological cancer.
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