Hexyl-aminolevulinate mediated photodynamic therapy: how to spare normal urothelium. An in vitro approach

Résumé Objectifs : La thérapie photodynamique a pour but la destruction sélective du tissu néoplasique par interaction de lumière, d'oxygène et d'une substance photosensibilisatrice (la Protoporphyrine IX dans notre étude). Malgré une accumulation sélective du photosensibilisateur dans le tissu tumoral, la thérapie photodynamique du carcinome urothélial de la vessie peut endommager les cellules normales de l'épithélium urinaire. La prévention de ces lésions est importante pour la régénération de la muqueuse. Notre étude sur un modèle in vitro d'urothélium porcin étudie l'influence de la concentration du photosensibilisateur, des paramètres d'irradiation et de la production d'intermédiaires réactifs de l'oxygène (ROS) sur les effets photodynamique. Le but était de déterminer les conditions seuil pour épargner l'urothélium sain. Méthode: Dans une chambre de culture transparente à deux compartiments, des muqueuses vésicales de porc maintenues en vie ont été incubées avec une solution d'hexyl-aminolévulinate (HAL), le précurseur de la Protoporphyrine IX. Ces muqueuses ont ensuite été irradiées avec des doses lumineuses croissantes en lumière bleue et en lumière blanche, et les altérations cellulaires ont été évaluées par microscopie électronique à balayage et par un colorant fluorescent, le Sytox green. Nous avons également évalué la production d'intermédiaires réactifs de l'oxygène parla mesure de la fluorescence intracellulaire de Rhodamine 123 (R123), produit de l'oxydation de la Dihydrorhodamine 123 (DHR123) non fluorescente. Ces valeurs ont été corrélées avec celles du photo blanchiment de la PAIX. Résultats : Le taux de mortalité cellulaire était dépendant de la concentration de PAIX. Après 3 heures d'incubation, la valeur seuil de dose lumineuse pour la lumière bleu était de 0.15 et 0.75 J/cm2 (irradiance 30 et 75 mW/cm2, respectivement) et pour la lumière blanche de 0.55 J/cm2 (irradiante 30 mW/cm2). Le taux de photo blanchiment était inversement proportionnel à l'irradiante. Le système de détection des intermédiaires réactifs de l'oxygène DHR123/R123 a démontré une bonne corrélation avec les valeurs seuil pour toutes les conditions d'irradiation utilisées. Conclusions : Nous avons déterminé les doses lumineuses permettant d'épargner 50% des cellules urothéliales saines. L'utilisation d'une faible irradiante associée à des systèmes permettant de mesurer la production d'intermédiaires réactifs de l'oxygène dans les tissus irradiés pourrait améliorer la dosimétrie in vivo et l'efficacité de la thérapie photodynamique. Abstract Background and Objectives: Photodynamic therapy of superficial bladder cancer may cause damages to the normal surrounding bladder wall. Prevention of these is important for bladder healing. We studied the influence of photosensitizes concentration, irradiation parameters and production of reactive oxygen species (ROS) on the photodynamically induced damage in the porcine urothelium in vitro. The aim was to determine the threshold conditions for the cell survival. Methods: Living porcine bladder mucosae were incubated with solution of hexylester of 5-aminolevulinic acid (HAL). The mucosae were irradiated with increasing doses and cell alterations were evaluated by scanning electron microscopy and by Sytox green fluorescence. The urothelial survival score was correlated with Protoporphyrin IX (PpIX) photobleaching and intracellular fluorescence of Rhodamine 123 reflecting the ROS production. Results: The mortality ratio was dependent on PpIX concentration. After 3 hours of incubation, the threshold radiant exposures for blue light were 0.15 and 0.75 J/cm2 (irradiance 30 and 75 mW/cm2, respectively) and for white light 0.55 J/cm2 (irradiance 30 mW/cm2). Photobleaching rate increased with decreasing irradiance. Interestingly, the DHR123/R123 reporter system correlated well with the threshold exposures under all conditions used. Conclusions: we have determined radiant exposures sparing half of normal urothelial cells. We propose that the use of low irradiance combined with systems reporting the ROS production in the irradiated tissue could improve the in vivo dosimetry and optimize the PDT.

Plan de la partie de la route dép[artementa]le n°4 d'Ambérieux à Belley depuis la maison Thermet jusqu'au sommet de la rampe de la Darde, de la rivière de Furand et du coteau boisé et hautiné qui sépare la vallée de Furand d'avec la gorge de la Darde : Département de l'Ain : Arrondissement de Belley / Dressé par Mr Marchand, conducteur au corps royal des ponts et chaussées à Belley (Ain)

Échelle(s) : 1:2 500

Spare non-occupational HIV post-exposure prophylaxis by active contacting and testing of the source person.

OBJECTIVE: HIV-1 post-exposure prophylaxis (PEP) is frequently prescribed after exposure to source persons with an undetermined HIV serostatus. To reduce unnecessary use of PEP, we implemented a policy including active contacting of source persons and the availability of free, anonymous HIV testing ('PEP policy'). METHODS: All consultations for potential non-occupational HIV exposures i.e. outside the medical environment) were prospectively recorded. The impact of the PEP policy on PEP prescription and costs was analysed and modelled. RESULTS: Among 146 putative exposures, 47 involved a source person already known to be HIV positive and 23 had no indication for PEP. The remaining 76 exposures involved a source person of unknown HIV serostatus. Of 33 (43.4%) exposures for which the source person could be contacted and tested, PEP was avoided in 24 (72.7%), initiated and discontinued in seven (21.2%), and prescribed and completed in two (6.1%). In contrast, of 43 (56.6%) exposures for which the source person could not be tested, PEP was prescribed in 35 (81.4%), P < 0.001. Upon modelling, the PEP policy allowed a 31% reduction of cost for management of exposures to source persons of unknown HIV serostatus. The policy was cost-saving for HIV prevalence of up to 70% in the source population. The availability of all the source persons for testing would have reduced cost by 64%. CONCLUSION: In the management of non-occupational HIV exposures, active contacting and free, anonymous testing of source persons proved feasible. This policy resulted in a decrease in prescription of PEP, proved to be cost-saving, and presumably helped to avoid unnecessary toxicity and psychological stress.

Benchmarking Spare Parts' Logistics Process

Työn tavoitteena oli selvittää SBU:n varastovaraosien logistinen prosessin tämänhetkinen tilanne verrattuna muihin ja sitä kautta oppia uusia tehokkaita tapoja hallita sitä sekä parantaa sen kilpailukykyä. Selvittäminen tapahtui benchmarkkaamalla SBU:n varastovaraosien logistinen prosessi kahteen sen kilpailijaan ja viiteen muuhun ei kilpailija yritykseen. Bechmarking -aineiston kerääminen tapahtui pääasiassa Inter netin, haastattelujen, bechmarking -kyselyn ja yritysvierailujen avulla. Tulosten vertailu ja analysointi perustui kerättyyn aineistoon. Kriteereiksi lopullista vertailua varten valittiin seikat, joihin liittyvä tieto oli saatavilta suurimmalta osalta bechmarking -yrityksistä. Tuloksena lopullisesta vertailusta muodostettiin "ranking" lista, jossa yritykset on laitettu paremmuus-järjestykseen. Tässä vertailussa SBU sijoittui viimeiseksi ja SBU varastovaraosien logistisessa prosessissa havaittiin olevan useita parannuskohteita. Joka tapauksessa SBU sai paljon tietoa siitä, kuinka muut yritykset hallitsevat prosessinsa ja kuinka SBU:n tulisi tulevaisuudessa hallita oma logistinen prosessinsa ja kuinka se voisi sitä kautta lisätä kilpailukykyään.

Value added logistical support service Part 2. Outsourcing process of spare part logistics in metal industry

The aim of this research study was to find out guidelines for outsourcing of logistics processes. The study was outlined to spare parts and `business-to-business' (B2B) markets in metal industry. This study can be applied as a manual for outsourcing especially warehousing and transportation activities. The study also touches other important areas of spare part logistics like manufacturing, customer service, procurement, quality control, reverse and recycling logistics, logistics technologies and valueadded services. The method of study consisted of three areas. Firstly exchanging views with logistics experts in participating companies, and secondly compiling material based on author's practical experience in logistics business with several international and domestic logistics service providers and vendors. Thirdlythe study includes also references to literature material. Due to the fact thatthe outsourcing of logistics functions can be handled widely and from differentpoint of views, in this study it is concentrated mainly on giving general levelguidelines for defining logistics strategy, hints both for tendering process and implementation project, and not forgetting the aftercare of business partnership.

Logistics in Pump Manufacturer's Spare Part Distribution Network

Tässä diplomityössä käsitellään pumppujen maailmanlaajuista varaosa-jakelua. Työn pääpaino on varaosien moniportaisen jakeluverkon toimitusketjun logistiikassa. Asiakaspalvelussa varaosien nopea saatavuus on ratkaisevassa asemassa, jotta asiakkaiden tehtaiden käynnissäpito voidaan turvata. Työn tavoitteena oli kehittää Ahlström Pumpuille uusi globaali toimintamalli varaosien jakeluun. Tämä uusi varaosien jakelumalli on kehitetty pääasiassa sopimusasiakkaille, jotka ovat halukkaita ulkoistamaan varaosatoimintonsa. Mallia sovelletaan käytäntöön varaosien jakelussa ensiksi Suomessa ja Ruotsissa. Myöhemmin on tarkoitus kopioida mallia myös muualle. Malli on pyritty rakentamaan siten, että siihen voidaan helposti liittää muita Ahlström Pumppujen tarjoamia palveluita. Työssä koottu materiaali perustuu pääasiassa haastatteluihin, palavereihin, erilaisiin sisäisiin raportteihin, kirjallisuuteen ja itsenäiseen selvitystyöhön. Työssä on myös tutustuttu kolmen eri yrityksen after-sales- ja varaosatoimintaan.

Spare part business analysis and development

The purpose of this Thesis was to comprehensively analyze and develop the spare part business in Company Oy’s five biggest product groups by searching development issues related to single spare parts’ supply chains as well as the spare part business process, make implementation plans for them and implement the plans when possible. The items were classified based on special characteristics of spare parts and on their actual sales volumes. The created item classes were examined for finding improvement possibilities. Management strategies for classified items were suggested. Vendors and customers were analyzed for supporting the comprehensive supply network development work. The effectiveness of the current spare part business process was analyzed in co-operation with the spare part teams in three business unit locations. Several items were taken away from inventories as uselessly stocked items. Price list related to core items with one of the main product group’s core item manufacturer was suggested to be expanded in Town A. Refinement equipment seal item supply chain management was seen important to develop in Town B. A new internal business process model was created for minimizing and enhancing the internal business between Company’s business units. SAP inventory reports and several other features were suggested to be changed or developed. Also the SAP data material management was seen very important to be developed continuously. Many other development issues related to spare parts’ supply chains and the work done in the business process were found. The need for investigating the development possibilities deeper became very clear during the project.

From electronic spare part catalog to eBusiness: Finding the best practices

Companies and organizations business activities rely on information. IT systems that manage master data must provide the highest level of service, world-class scalability and reliable information. This study discusses product information and how it can support the creation of a spare part catalog and the launching of eBusiness. The study consists of a theoretical and empirical part. The theoretical part contains a literature review and a framework for the analysis. For the empirical study two companies were selected and their information management processes were studied and analyzed based on the framework. The empirical results indicate that the challenges the companies face reflect the ones that can be found in the literature study. The results of the empirical study also show that the companies had recognized the issues which need to be developed and had recognized trends in eBusiness and product information management.

Assessment of purchasing maturity in spare parts supply chain

To describe the change of purchasing moving from administrative to strategic function academics have put forward maturity models which help practitioners to compare their purchasing activities to industry top performers and best practices. However, none of the models aim to distinguish the purchasing maturity from the after-sales point of view, even though after-sales activities are acknowledged as a relevant source of revenue, profit and competitive advantage in most manufacturing firms. The maturity of purchasing and supply management practices have a large impact to the overall performance of the spare parts supply chain and ultimately to the value creation and relationship building for the end customer. The research was done as a case study for a European after-sales organization which is part of a globally operating industrial firm specialized in heavy machinery. The study mapped the current state of the purchasing practices in the case organization and also distinguished the relevant areas for future development. The study was based on the purchasing maturity model developed by Schiele (2007) and investigated also how applicable is the maturity model in the spare parts supply chain context. Data for the assessment was gathered using five expert interviews inside the case organization and other parties involved in the company’s spare parts supply chain. Inventory management dimension was added to the original maturity model in order to better capture the important areas in a spare parts supply chain. The added five questions were deduced from the spare parts management literature and verified as relevant areas by the case organization’s personnel. Results indicate that largest need for development in the case organization are: better collaboration between sourcing and operative procurement functions, use of installed base information in the spare parts management, training plan development for new buyers, assessment of aligned KPI’s between the supply chain parties and better defining the role of after-sales sourcing. The purchasing maturity model used in this research worked well in H&R Leading, Controlling and Inventory Management dimensions. The assessment was more difficult to conduct in the Supplier related processes, Process integration and Organizational structure –dimensions, mainly because the assessment in these sections would for some parts require more company-wide assessment. Results indicate also that the purchasing maturity model developed by Schiele (2007) captures the relevant areas in the spare parts supply as well.

Supplier Delivery Quality Evaluation in Maintenance Supporting Spare Part Business

The focus of this thesis is the issues related to the operational purchasing level supply chain process. Due to this limitation, the physical product quality issues do not belong to the primary concerns of this thesis, whereas the bilateral processes between the supplier and the purchasing organizations are of interest. Also, the issues related to the delivery timing are excluded from the study. Because the perspective is on the issues involved in the supply chain operations, the bilateral communication issues between supplier representative and purchaser are also considered.

Global Spare Parts Supply Chain Analysis

In today’s global industrial service business, markets are dynamic and finding new ways of value creation towards customers has become more and more challenging. Customer orientation is needed because of the demanding after-sales business which is both quickly changing and stochastic in nature. In after-sales business customers require fast and reliable service for their spare part needs. This thesis objective is to clarify this challenging after-sales business environment and find ways to increase customer satisfaction via balanced measurement system which will help to find possible targets to reduce order cycle times in a large metal and mineral company Outotec (Filters)’ Spare Part Supply business line. In case study, internal documents and data and numerical calculations together with qualitative interviews with different persons in key roles of Spare Part Supply organizations are used to analyze the performance of different processes from the spare parts delivery function. The chosen performance measurement tool is Balanced Scorecard which is slightly modified to suit the lead time study from customer’s perspective better. Findings show that many different processes in spare parts supply are facing different kind of challenges in achieving the lead time levels wanted and that these processes’ problems seem to accumulate. Findings also show that putting effort in supply side challenges and information flows visibility should give the best results.

Finding Methods for Recognizing and Classifying Spare Part Criticality – Case Full Deposit Stripping Machines

The aim of this Master’s thesis is to find a method for classifying spare part criticality in the case company. Several approaches exist for criticality classification of spare parts. The practical problem in this thesis is the lack of a generic analysis method for classifying spare parts of proprietary equipment of the case company. In order to find a classification method, a literature review of various analysis methods is required. The requirements of the case company also have to be recognized. This is achieved by consulting professionals in the company. The literature review states that the analytic hierarchy process (AHP) combined with decision tree models is a common method for classifying spare parts in academic literature. Most of the literature discusses spare part criticality in stock holding perspective. This is relevant perspective also for a customer orientated original equipment manufacturer (OEM), as the case company. A decision tree model is developed for classifying spare parts. The decision tree classifies spare parts into five criticality classes according to five criteria. The criteria are: safety risk, availability risk, functional criticality, predictability of failure and probability of failure. The criticality classes describe the level of criticality from non-critical to highly critical. The method is verified for classifying spare parts of a full deposit stripping machine. The classification can be utilized as a generic model for recognizing critical spare parts of other similar equipment, according to which spare part recommendations can be created. Purchase price of an item and equipment criticality were found to have no effect on spare part criticality in this context. Decision tree is recognized as the most suitable method for classifying spare part criticality in the company.