The concept of distance is a fundamental notion that forms a basis for the orientation in space. It is related to the scientific measurement process: quantitative measurements result in numerical... Show moreThe concept of distance is a fundamental notion that forms a basis for the orientation in space. It is related to the scientific measurement process: quantitative measurements result in numerical values, and these can be immediately translated into distances. Vice versa, a set of mutual distances defines an abstract Euclidean space. Each system is thereby represented as a point, whose Euclidean distances approximate the original distances as close as possible. If the original distance measures interesting properties, these can be found back as interesting patterns in this space. This idea is applied to complex systems: The act of breathing, the structure and activity of the brain, and dynamical systems and time series in general. In all these situations, optimal transportation distances are used; these measure how much work is needed to transform one probability distribution into another. The reconstructed Euclidean space then permits to apply multivariate statistical methods. In particular, canonical discriminant analysis makes it possible to distinguish between distinct classes of systems, e.g., between healthy and diseased lungs. This offers new diagnostic perspectives in the assessment of lung and brain diseases, and also offers a new approach to numerical bifurcation analysis and to quantify synchronization in dynamical systems. Show less
The term primary cutaneous B-cell lymphomas refers to a heterogeneous group of B-cell non-Hodgkin lymphomas, that present in the skin without evidence of extracutaneous disease at the time of... Show moreThe term primary cutaneous B-cell lymphomas refers to a heterogeneous group of B-cell non-Hodgkin lymphomas, that present in the skin without evidence of extracutaneous disease at the time of diagnosis. In recent years, there has been considerable debate regarding the classification and terminology of the group of primary cutaneous B-cell lymphomas and different classification schemes were used. In the new WHO-EORTC consensus classification for cutaneous lymphomas published in 2005, three major groups of primary cutaneous B-cell lymphoma are distinguished: primary cutaneous marginal zone B-cell lymphoma and primary cutaneous follicle center lymphoma with a good prognosis, and primary cutaneous diffuse large B-cell lymphoma, leg type with an intermediate prognosis. Studies presented in this thesis focus on three aspects of these primary cutaneous B-cell lymphomas: (1) the clinical usefulness of the WHO-EORTC classification in daily practice, (2) the validity of prognostic parameters reported in previous studies and identified in patient groups classified according to previously used classification schemes and (3) optimal management for the different types of primary cutaneous B-cell lymphomas as defined in the WHO-EORTC classification. Show less
Primair cutane B-cel lymfomen (CBCL) vormen een heterogene groep van non-Hodgkin lymfomen die zich primair in de huid manifesteren zonder aanwezigheid van extracutane lokalisaties. Volgens de in... Show morePrimair cutane B-cel lymfomen (CBCL) vormen een heterogene groep van non-Hodgkin lymfomen die zich primair in de huid manifesteren zonder aanwezigheid van extracutane lokalisaties. Volgens de in Nederland toegepaste EORTC-classificatie kunnen 3 typen CBCL onderscheiden worden: het primair cutaan immunocytoom of marginale zone B-cel lymfoom, het primair cutaan follikelcentrumcel lymfoom en het primair cutaan grootcellig B-cel lymfoom van het been. De studies in dit proefschrift hebben door middel van clinicopathologisch onderzoek en verschillende moleculair biologische technieken (waaronder genexpressie analyse, array-CGH en FISH-analyse) geresulteerd in de identificatie van een aantal nieuwe diagnostische en prognostische markers en daarnaast specifieke genetische kenmerken van de verschillende typen CBCL aangetoond. Deze resultaten hebben in de eerste plaats geleid tot een betere definitie van de verschillende typen CBCL. Daarnaast hebben de resultaten van deze studies een belangrijke rol gespeeld in de totstandkoming van een nieuwe consensus classificatie voor cutane lymfomen in 2005. In deze WHO-EORTC classificatie worden de volgende 3 belangrijkste typen CBCL onderscheiden: het primair cutaan marginale zone B-cel lymfoom, het primair cutaan follikelcentrum lymfoom en het primair cutaan grootcellig B-cel lymfoom, been type. Show less
The feasibility of earprint individualization depends upon the amount of variation in prints of different ears, but also upon that in prints of a single ear. In order to determine the limits to... Show moreThe feasibility of earprint individualization depends upon the amount of variation in prints of different ears, but also upon that in prints of a single ear. In order to determine the limits to intra-individual variation, we need to explore its potential causes. As the amount of force that is applied by the ear to the listening surface influences the appearance of the earprint, we investigated factors potentially affecting this force, such as the level and frequency of a target sound, and the level of ambient noise. We also investigated whether presence or absence of a target sound was of influence. Additionally, we explored if the duration of listening, and whether the ear had been recently cleaned or not, affected the appearance of an earprint. To evaluate the extent to which features may vary with passing time, we further attempted to determine the rate of growth of the external ear during adult life. As a next step, we then compared realistic intra-individual variation in earprints with a very small degree of inter-individual variation, i.e., that in prints of identical twins. To do so, we explored a method to fully automatically analyze prints. To our knowledge, this was the first time that any method capable of fully automated earprint comparisons has been described. Show less
Primary cutaneous lymphoma form a seperate group of non-Hodgkin lymphoma. Apart from the usual nodal presentation of a lymphoma, less frequently a lymphoma develops in an extranodal site. The skin... Show morePrimary cutaneous lymphoma form a seperate group of non-Hodgkin lymphoma. Apart from the usual nodal presentation of a lymphoma, less frequently a lymphoma develops in an extranodal site. The skin is, after the gastrointestinal tract, the most frequent site of extranodal lymphoma. If the skin is the primary site of involvement, i.e. no extracutaneous sites are involved at diagnosis, these lymphomas are called primary cutaneous lymphoma. In this thesis different types of primary cutaneous lymphoma are evaluated and discussed. In chapter 2 a large group of primary cutaneous CD30+ lympoproliferations is described and compared with a group of systemic CD30+ ALCL with skin localisations. Lymphomatoid papulosis and primary cutaneous CD30+ CTCL are closely related conditions and should be considered as a spectrum, with a comparable, excellent, prognosis. Multiagent chemotherapy (MAC) could not induce long lasting remissions, in fact all patients treated with MAC developed one or more (cutaneous) relapses. Therefor MAC is only indicated in case of extracuteneous localisations. In chapter 3 a group of CD30-negative T-cell lymphomas presenting in the skin that could not be diagnosed as MF, SS or SPTL are evaluated. In this group there were few survivors, apart from a rare group of patients with primary cutaneous lymphoma with small-medium sized CD4+/CD8-neoplastic T-cells (less than 30% large cells). In particular, patients with localized disease had an excellent prognosis. In chapter 4 haematological malignancies presenting in the skin and expressing CD56 were collected, both from the Dutch cutaneous lymphoma group and literature. In general these types of malignancies had a poor prognosis, except for patients with primary cutaneous CD30+ LPD, that showed a similar good prognosis as CD56-negative cases. Most cases belonged to the group of nasal-type NK/T-cell lymphoma and the group of CD4+, CD56+ hematodermic neoplasm (formerly also designated as blastic NK-cell lymphoma. In addition, CD56 was expressed in some SPTL, rare primary cutaneous CD30-negative large T-cell lymphomas, skin localisations of acute myeloid leukemia and CD30+ CTCL. In most of these groups CD56 expression did not affect prognosis. However, in SPTL CD56 expression proved a marker for gamma/delta T-cell origin and these cases showed a poorer prognosis as compared to SPTL with an alpha/beta phenotype (that were usually CD56-negative). In the new WHO-EORTC classification the category of SPTL only includes cases with an alpha/beta-positive phenotype, whereas cases with a gamma/delta positive phenotype are included in the provisional category of cutaneous gamma/delta-positive T-cell lymphoma. In chapter 5 a rare case of lymphomatoid papulosis with CD56-expression was presented and the frequency of co-expression of CD56 in primary cutaneous CD30+ LPD was analyzed. CD56 expression was found in approximately 10% of CD30+ LPD (both LyP and primary CD30+ CTCL). However, these CD56+ cases were not found to have a different prognosis from CD56 negative cases. In chapter 6 a European multicenter study on primary cutaneous large B-cell lymphomas is presented. Patients with primary cutaneous large B-cell lymphoma of the leg showed a poorer prognosis as patients with primary cutaneous follicle center cell lymphoma (PCFCCL). Moreover, round cell morphology was identified as a poor prognostic parameter. Although this was closely related to presentation on the leg(s), also in the group of PCFCCL the presence of a predominance of cells with round nuclei (centroblasts and immunoblasts) was associated with a poorer prognosis. The results of this study contributed to a new category in the WHO-EORTC classification, designated primary cutaneous large B-cell lymphoma (PCLBCL), leg-type, indicating that both patients with the classical presentation on the leg(s) as patients showing the same morphology and immunophenotype (bcl-2+, Mum-1/ IRF4+) on other sites are included in this group. Presentation with multifocal lesions proved to be a poor prognostic parameter for PCLBCL-leg-type, but not for PCFCCL. In chapter 7 treatment results in multifocal primary CBCL were analyzed. The main question in this study was if PCFCCL presenting with multifocal skin lesions should be treated with MAC. The study showed that MAC is only indicated in PCLBCL, leg-type and not in (multifocal) PCFCCL. Radiotherapy on multiple sites appeared equally effective as MAC in these patients. In chapter 8 the frequency of CNS-involvement in CBCL patients of the Dutch cutaneous lymphoma group. was evaluated. The frequency was low. Only 4/140 patients with a primary CBCL developed CNS involvement in the course of their disease. Interestingly 3 of these 4 patients were PCFCCL, a lymphoma usually with an excellent prognosis. Only 4 disease related deaths were reported in this group of which 3 with CNS involvement. The reason for this relatively high prevalence of CNS involvement in PCFCCL is unclear. The studies presented in this thesis have provided important information, which has contributed to the recent development of the WHO-EORTC classification. Moreover, they have contributed to updated guidelines for the treatment of the different types of primary cutaneous lymphomas, as presented in TABLE 2 in chapter 9. Show less
