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- Bornefalk Hermansson, Anna, 1971-
(författare)
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Resampling Evaluation of Signal Detection and Classification : With Special Reference to Breast Cancer, Computer-Aided Detection and the Free-Response Approach
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The first part of this thesis is concerned with trend modelling of breast cancer mortality rates. By using an age-period-cohort model, the relative contributions of period and cohort effects are evaluated once the unquestionable existence of the age effect is controlled for. The result of such a modelling gives indications in the search for explanatory factors. While this type of modelling is usually performed with 5-year period intervals, the use of 1-year period data, as in Paper I, may be more appropriate.The main theme of the thesis is the evaluation of the ability to detect signals in x-ray images of breasts. Early detection is the most important tool to achieve a reduction in breast cancer mortality rates, and computer-aided detection systems can be an aid for the radiologist in the diagnosing process.The evaluation of computer-aided detection systems includes the estimation of distributions. One way of obtaining estimates of distributions when no assumptions are at hand is kernel density estimation, or the adaptive version thereof that smoothes to a greater extent in the tails of the distribution, thereby reducing spurious effects caused by outliers. The technique is described in the context of econometrics in Paper II and then applied together with the bootstrap in the breast cancer research area in Papers III-V.Here, estimates of the sampling distributions of different parameters are used in a new model for free-response receiver operating characteristic (FROC) curve analysis. Compared to earlier work in the field, this model benefits from the advantage of not assuming independence of detections in the images, and in particular, from the incorporation of the sampling distribution of the system's operating point.Confidence intervals obtained from the proposed model with different approaches with respect to the estimation of the distributions and the confidence interval extraction methods are compared in terms of coverage and length of the intervals by simulations of lifelike data.
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| 2. |
- Olsson-Strömberg, Ulla, et al.
(författare)
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Imatinib activity in vitro in tumor cells from patients with chronic myeloid leukemia in chronic phase and blast crisis
- 2006
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Ingår i: Anti-Cancer Drugs. - : Ovid Technologies (Wolters Kluwer Health). - 0959-4973 .- 1473-5741. ; 17:6, s. 631-639
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Tidskriftsartikel (refereegranskat)abstract
- The aims of this study were to evaluate the feasibility of using the non-clonogenic fluorometric microculture cytotoxicity assay in drug sensitivity testing of tumor cells from patients with chronic myeloid leukemia. In nine samples (six chronic phase, three blast crisis), the drug sensitivities in tumor cells from blood versus from bone marrow and fresh tumor cells versus cryopreserved were compared. In 26 samples obtained in chronic phase (pretreatment), in six samples from patients in blast crisis and in the K 562 cell line, the activity of imatinib alone and in combination with cytarabine, vincristine, daunorubicin, interferon, arsenic trioxide and homoharringtonine was evaluated. All chronic myeloid leukemia chronic phase samples were sensitive to imatinib, with a mean IC50 at 10.3 mumol/l. The chronic myeloid leukemia samples from blast crisis (n=6) were significantly more sensitive to imatinib than the samples from chronic phase (n=26) (P<0.05), with an IC50 mean at 0.4 mumol/l. In blast crisis samples, significant positive interaction effects were observed between imatinib and all other tested drugs except for interferon. In chronic phase samples, interferon, daunorubicin and arsenic trioxide were the drugs with the highest frequency of positive interactions with imatinib (P<0.05). We conclude that the fluorometric microculture cytotoxicity assay may be a useful method for drug sensitivity testing in chronic myeloid leukemia patient samples from both chronic phase and blast crisis, and that testing primary tumor cells may have advantages over cell line studies. Imatinib shows a higher in vitro activity and more positive drug interactions in cells from blast crisis than chronic phase chronic myeloid leukemia patients. Combinations between imatinib and interferon, daunorubicin and arsenic trioxide may be interesting for future clinical trials in patients with chronic myeloid leukemia chronic phase.
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| 3. |
- Sanchez, Javier, et al.
(författare)
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Surface-adsorbed fibrinogen and fibrin may activate the contact activation system
- 2008
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Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 122:2, s. 257-263
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: This study was designed to investigate whether fibrinogen, soluble desAA-fibrin, and insoluble desAABB-fibrin are able to induce clotting by triggering the plasma contact activation system when adsorbed to polystyrene. MATERIALS AND METHODS: The above-mentioned substances were individually prepared on polystyrene meshwork squares, and then exposed to a purified FXII solution or non-calcium containing plasma (citrated and dialyzed normal pooled plasma) in polystyrene cuvettes coated with surface-immobilized heparin, to completely block contact activation and the coagulation mechanism that might be induced by the cuvette surfaces. Sodium glass beads were used as the reference material. RESULTS: On exposure to purified FXII solution and plasma, all the tested materials adsorbed and activated FXII to varying degrees. This activation led to the formation of FXIa in the exposed plasma, with the highest activation occurring upon exposure to glass, desAA-fibrin and desAABB-fibrin and the lowest upon exposure to fibrinogen-adsorbed or unmodified polystyrene meshwork squares. Following recalcification, in cuvettes with surface-immobilized heparin, a spectrophotometric assay showed that the surface-exposed plasma aliquots clotted within 5 min after contact with glass, within 10 to 15 min after contact with the two forms of fibrin, and somewhat longer after contact with adsorbed fibrinogen. The longest lag phase, close to 20 min, occurred in plasma exposed to unmodified polystyrene meshwork. Whole blood deposited in surface heparinized cuvettes directly from the cubital vein did not clot during the observation time (2 h). CONCLUSIONS: These results indicate that domains induced by conformational changes in adsorbed fibrinogen and fibrin are capable of activating adsorbed proenzymes and that various forms of fibrin are considerably stronger activators of the contact activation system than are adsorbed fibrinogen or a polystyrene meshwork. The delayed coagulation in plasma exposed to the unmodified polystyrene meshwork can be explained by a two-step process: first, adsorption of fibrinogen, and second, activation of FXII. Under our experimental conditions, the adsorption and activation of FXII on fibrinogen and fibrin seems to be an important mechanism for triggering coagulation.
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