Assessment of the added value of the Twente Photoacoustic Mammoscope in breast cancer diagnosis\ud

Purpose: Photoacoustic (PA) imaging is a recently developed breast cancer imaging technique. In order to enhance successful clinical implementation, we quantified the potential clinical value of different scenarios incorporating PA imaging by means of multi-criteria analysis. From this analysis, the most promising area of application for PA imaging in breast cancer diagnosis is determined, and recommendations are provided to optimize the design of PA imaging. - \ud Methods: The added value of PA imaging was assessed in two areas of application in the diagnostic track. These areas include PA imaging as an alternative to x-ray mammography and ultrasonography in early stage diagnosis, and PA imaging as an alternative to Magnetic Resonance Imaging (MRI) in later stage diagnosis. The added value of PA imaging was assessed with respect to four main criteria (costs, diagnostic performance, patient comfort and risks). An expert panel composed of medical, technical and management experts was asked to assess the relative importance of the criteria in comparing the alternative diagnostic devices. The judgments of the experts were quantified based on the validated pairwise comparison technique of the Analytic Hierarchy Process, a technique for multi-criteria analysis. Sensitivity analysis was applied to account for the uncertainty of the outcomes. - \ud Results: Among the considered alternatives, PA imaging is the preferred technique due to its non-invasiveness, low cost and low risks. However, the experts do not expect large differences in diagnostic performance. The outcomes suggest that design changes to improve the diagnostic performance of PA imaging should focus on the quality of the reconstruction algorithm, detector sensitivity, detector bandwidth and the number of wavelengths used. - \ud Conclusion: The AHP method was useful in recommending the most promising area of application in the diagnostic track for which PA imaging can be implemented, this being early diagnosis, as a substitute for the combined use of x-ray mammography and ultrasonography

Rupture of the arterial wall causes deflection in pressure time course during ex vivo balloon angioplasty

A relation between restenosis and arterial lesions resulting from balloon angioplasty has been suggested in literature. Nevertheless, it is unclear to what extent angioplasty-induced arterial wall lesions contribute to the occurrence of restenosis. One problem is that arterial ruptures cannot be detected during balloon inflation. This study describes a method to detect ruptures in the arterial wall, based on deflections observable in the development of the balloonpressure. We performed ex vivo angioplasty with constant strain rate on 28 human femoral artery segments, showing deflections in 21 cases. In 20 cases wall rupture was confirmed histologically. From seven cases not showing deflections, four showed intact wall at microscopy. These figures result in a selectivity of the proposed method of 87 ± 7% and a predictive value of the positive test of 95 ± 5%. We conclude that this method can enhance detection of arterial rupture during ex vivo angioplasty and may become important clinically

Integrating action learning practices into executive coaching to enhance business results

Coaching-based development is growing in prominence as a means of enhancing the achievement of leadership outcomes in Australian business. This article seeks to demonstrate how the application of the practices associated with action learning can be applied to support the achievement of practical outcomes within group-based executive coaching, namely a more rigorous focus on business results. The work draws on an illustrative case study: a group-coaching program conducted with the executive leadership team of an industry-based service organisation. The theoretical and methodological basis of coaching and action learning are explored and contrasted with the conclusion that an integrated approach has the capacity to support coaching participants to achieve extensive developmental and practical outcomes

Rebel en dame : biografie van Top Naeff

Top Naeff (1878-1953) is in Nederland beroemd om haar meisjesboek School-Idyllen. Verder schreef ze romans en novellen. Minder bekend is dat ze een toonaangevend toneelcritica was.Dit proefschrift geeft niet alleen een beeld van Naeff als schrijfster van meisjesboeken en proza voor volwassenen, maar vooral van een vrouw met een hevige passie voor toneel, die streed voor de belangen van de acteur en regisseur Willem Royaards. De biografie beschrijft ook de geheime liefde van Naeff voor Royaards, en toont aan dat het overgrote deel van Naeffs romans en verhalen de literaire verwerking is van haar dubbelleven, haar frustraties en de uiteindelijke acceptatie van alle tekort. Daarmee biedt deze biografie, zoals een schrijversbiografie dient te doen, een verhelderend inzicht in het oeuvre van Top Naeff.Vrijwel alle vrouwelijke auteurs van het interbellum werden door met name de Forum-generatie denigrerend betiteld als auteurs van ‘damesromans’. De biografie nuanceert dit beeld wat Top Naeff betreft overtuigend; criticus Menno ter Braak had respect voor Naeff en haar werk en bewonderde naar ‘superieure ironie’.Deze biografie biedt veel nieuwe feiten en inzichten, een analytisch beeld van Naeff als toneelcritica, een positiebepaling in haar tijd, een verband tussen leven en werk en een nuancering waar het de beeldvorming in literaire handboeken en encyclopedieën betreft.LEI Universiteit LeidenNederlands Letterenfonds Familievereniging VriesendorpModern and Contemporary Studie

From genes to function in autoimmunity - a salty story

Autoimmunity is a condition in which the ability to tolerate self breaks down, resulting in immune responses against the body’s own healthy cells and tissues. Autoimmune diseases are complex and multifactorial, and both genetic and environmental factors are known to play a crucial role. Using animal models, it is possible to study different aspects of arthritis disease development in an environmentally and genetically controlled setting. In this thesis, I have investigated the effect of genetic risk loci and the single environmental factor sodium chloride (NaCl) on immune cell function and the development of autoimmune diseases using mouse models. In Paper I, using four congenic sub-loci within the arthritis susceptible Cia9 locus on chromosome 1, we found that the NOD.Q polymorphic Fc gamma receptor gene (FcγR) cluster located within sub-loci Cia9i and Cia9k, regulated arthritis. Polymorphic FcγR2b and FcγR4 were contained in both Cia9i and Cia9k, whereas Cia9i mice also carried polymorphic FcγR3. FcγR2b gene and protein expression were downregulated in Cia9i and Cia9k mice, whereas FcγR3 was upregulated in Cia9i mice and found downregulated in Cia9k mice compared to littermate control mice. This difference in FcγR3 expression affected killing by NK cells and phagocytosis by macrophages in vitro and PC61 antibody induced regulatory T cell depletion in vivo. Interestingly, arthritis development was regulated by interaction between FcγR2b and FcγR3 without affecting anti-collagen type II antibody secretion. These results show that polymorphisms in both FcγR2b and FcγR3 regulate the severity of inflammatory responses. In paper II, we investigated the importance of the system A family of amino acid transporters (SNAT), based on an identified congenic locus, as mediators of immune cell function and arthritis development. We demonstrated that SNAT proteins affect the initial stages of lymphocyte activation by regulating glutamine uptake in the presence of Na+, and that the effector phase of arthritis could be suppressed by blocking SNAT proteins. Paper III describes the effect of salt (e.g. NaCl) on the development of autoimmunity. Here we show that a moderate salt intake affects both T cell and macrophage phenotypes in vitro and ex vivo. However, these moderate levels of salt intake did not alter the development of T cell-dependent autoimmunity, whereas the dextran sulphate sodium (DSS)-induced colitis was exacerbated in mice pre-exposed to salt. Taken together, I have shown that the interplay between two genes enhances arthritis disease development, whereas a single environmental factor has no impact on arthritis despite triggering the immune system. These results contribute to the understanding of the mechanism behind complex multifactorial diseases as a small building block towards therapeutic intervention

Initial results of in vivo non-invasive cancer imaging in the human breast using near-infrared photoacoustics

Near-infrared photoacoustic images of regions-of-interest in 4 of the 5 cases of patients with symptomatic breasts reveal higher intensity regions which we attribute to vascular distribution associated with cancer. Of the 2 cases presented here, one is especially significant where benign indicators dominate in conventional radiological images, while photoacoustic images reveal vascular features suggestive of malignancy, which is corroborated by histopathology. The results show that photoacoustic imaging may have potential in visualizing certain breast cancers based on intrinsic optical absorption contrast. A future role for the approach could be in supplementing conventional breast imaging to assist detection and/or diagnosis.\ud \u