A novel TOPSIS–CBR goal programming approach to sustainable healthcare treatment

Cancer is one of the most common diseases worldwide and its treatment is a complex and time-consuming process. Specifically, prostate cancer as the most common cancer among male population has received the attentions of many researchers. Oncologists and medical physicists usually rely on their past experience and expertise to prescribe the dose plan for cancer treatment. The main objective of dose planning process is to deliver high dose to the cancerous cells and simultaneously minimize the side effects of the treatment. In this article, a novel TOPSIS case based reasoning goal-programming approach has been proposed to optimize the dose plan for prostate cancer treatment. Firstly, a hybrid retrieval process TOPSIS–CBR [technique for order preference by similarity to ideal solution (TOPSIS) and case based reasoning (CBR)] is used to capture the expertise and experience of oncologists. Thereafter, the dose plans of retrieved cases are adjusted using goal-programming mathematical model. This approach will not only help oncologists to make a better trade-off between different conflicting decision making criteria but will also deliver a high dose to the cancerous cells with minimal and necessary effect on surrounding organs at risk. The efficacy of proposed method is tested on a real data set collected from Nottingham City Hospital using leave-one-out strategy. In most of the cases treatment plans generated by the proposed method is coherent with the dose plan prescribed by an experienced oncologist or even better. Developed decision support system can assist both new and experienced oncologists in the treatment planning process

Prion Uptake in the Gut: Identification of the First Uptake and Replication Sites

After oral exposure, prions are thought to enter Peyer's patches via M cells and accumulate first upon follicular dendritic cells (FDCs) before spreading to the nervous system. How prions are actually initially acquired from the gut lumen is not known. Using high-resolution immunofluorescence and cryo-immunogold electron microscopy, we report the trafficking of the prion protein (PrP) toward Peyer's patches of wild-type and PrP-deficient mice. PrP was transiently detectable at 1 day post feeding (dpf) within large multivesicular LAMP1-positive endosomes of enterocytes in the follicle-associated epithelium (FAE) and at much lower levels within M cells. Subsequently, PrP was detected on vesicles in the late endosomal compartments of macrophages in the subepithelial dome. At 7–21 dpf, increased PrP labelling was observed on the plasma membranes of FDCs in germinal centres of Peyer's patches from wild-type mice only, identifying FDCs as the first sites of PrP conversion and replication. Detection of PrP on extracellular vesicles displaying FAE enterocyte-derived A33 protein implied transport towards FDCs in association with FAE-derived vesicles. By 21 dpf, PrP was observed on the plasma membranes of neurons within neighbouring myenteric plexi. Together, these data identify a novel potential M cell-independent mechanism for prion transport, mediated by FAE enterocytes, which acts to initiate conversion and replication upon FDCs and subsequent infection of enteric nerves

Uptake studies in rat Peyer's patches, cytotoxicity and release studies of alginate coated chitosan nanoparticles for mucosal vaccination

The design of particulate vaccine delivery systems, particularly for mucosal surfaces, has been a focus of interest in recent years. In this context, we have previously described the development and the characterization of a new nanosized delivery system, consisting of a model antigen adsorbed to chitosan particles and coated with sodium alginate. In the present work the ovalbumin release profiles from these coated nanoparticles in different pH buffers were investigated and compared to those of the uncoated particles. Cytotoxicity of the polymers and nanoparticles was assessed using the MTT assay. Finally, particle uptake studies in rat Peyer's patches were performed. It was demonstrated that the coating of the nanoparticles with sodium alginate not only avoided a burst release observed with uncoated particles but also increased the stability of the particles at pH 6.8 and 7.4 at 37 °C. At neutral pH, the release was lower than 5% after 3.5 h incubation in a low ionic strength buffer. For both, chitosan and alginate polymers, and for the nanoparticles, comparable cell viability data close to 100%, were obtained. Additionally, based on confocal laser scanning microscopy observations, it was shown that alginate coated nanoparticles were able to be taken up by rat Peyer's patches, rendering them suitable carriers for intestinal mucosal vaccination.http://www.sciencedirect.com/science/article/B6T3D-4K6CHRP-1/1/a257a285900ecde6d4747e1df67e1a8

Rechtstreeks verwijzen door de jeugdarts bij verdenking op heupdysplasie: het perspectief van ouders

Doel: Rechtstreeks verwijzen door de jeugdarts naar de tweede lijn lijkt zinvol bij verdenking op heupdysplasie. Screening op heupdysplasie vindt plaats door lichamelijk onderzoek en de identificatie van risicofactoren. Echografische screening blijkt medisch en economisch gezien te leiden tot betere uitkomsten. Als onderdeel van een studie naar de haalbaarheid van implementatie van echografische screening in Nederland is onderzocht hoe ouders het verwijstraject beoordelen afhankelijk van de manier waarop zij naar de orthopaedisch chirurg zijn verwezen - rechtstreeks of via de huisarts - bij verdenking op heupdysplasie. Methode: Een vragenlijst is ontwikkeld om de ervaring van ouders die verwezen zijn te meten. In totaal is de vragenlijst gestuurd naar 355 ouders van kinderen die verwezen zijn tussen januari 2008 en november 2008. Resultaten: De respons op de vragenlijst was 46,5%. Ouders waren meer tevreden wanneer zij door de jeugdarts rechtstreeks waren verwezen dan wanneer dat via de huisarts plaatsvond. De tijd tussen de verwijzing en de eerste afspraak bij de orthopaedisch chirurg was korter als kinderen rechtstreeks werden verwezen. Tot slot waren ouders meer tevreden als zij het verwijstraject als niet stressvol ervoeren en als het traject soepel verliep. Conclusie: Gebaseerd op de perceptie van ouders, geeft dit onderzoek een eerste indicatie dat, met inachtneming van een aantal belangrijke randvoorwaarden, rechtstreeks verwijzen in het geval van heupdysplasie wenselijk is