Cognitive behavioural skills for practice a model for delivery in the Irish mental health service.

This publication outlines a model of delivery for introductory level Cognitive Behavioural Therapy (CBT) training in the Mental Health Service, HSE South (Carlow, Kilkenny, South Tipperary, Waterford, Wexford). This model has proved useful in guiding the development of four introductory programmes during 2009 and 2010. As a result of this experience, we have amended and updated our programme delivery strategies. We see this process as organic and ever changing, thus these reflections are a snap shot of our current thinking which we have no doubt will evolve as we proceed with future programmes. This booklet will act as a guide for our upcoming programmes in 2010 and 2011 and we believe it may also offer guidance to others who will be involved in the delivery of CBT training within the Irish Mental Health Service.This resource was contributed by The National Documentation Centre on Drug Use.

Paternity and health services. Qualitative research on men's experiences during pregnancy, delivery and postpartum of theirs partners

Background: Little research has been carried out with regards to the inclusion of men during the birth process. The objective of this paper involves exploring the needs and expectations of the health services manifested by a group of fathers as a result of their experience during the birth process. Methods: Qualitative research was carried out in Granada in 2004 via individual interviews with fathers who showed shared responsibility in the upbringing. The profile is: employment, medium-high educational level, one or more child: 0-6 months of age. The transcript was subsequently submitted to hermeneutic analysis. Results: Some semantic constructs are: 1) Health Services do not concede the women as protagonists, 2) Birth process is depending on the body. Fathers can only support and fight for the relevance of men, 3) Men seem like “invisible”, 4) Health services inhibit their participation, and 5) have dealings with fathers according to their gender roles. The participants address the relationship between expectations of care during the birth process and unsatisfied demands, and the manner in which they employ the obstacles encountered within health services that inhibit their participation as arguments that confirm their separation from the process. Conclusions: This paper draws attention to the limited scope of the provision of healthcare during the birth process in terms of protagonism afforded to fathers. Indeed, despite their requisitory discourse, the interviewees manifest contradictory attitudes in the face of changes that require them to make commitments. We identify elements that could be improved to adapt services to the needs of fathers and vice versa.

Exogenous mRNA delivery and bioavailability in gene transfer mediated by piggyBac transposition.

BACKGROUND: Up to now, the different uptake pathways and the subsequent intracellular trafficking of plasmid DNA have been largely explored. By contrast, the mode of internalization and the intracellular routing of an exogenous mRNA in transfected cells are poorly investigated and remain to be elucidated. The bioavailability of internalized mRNA depends on its intracellular routing and its potential accumulation in dynamic sorting sites for storage: stress granules and processing bodies. This question is of particular significance when a secure transposon-based system able to integrate a therapeutic transgene into the genome is used. Transposon vectors usually require two components: a plasmid DNA, carrying the gene of interest, and a source of transposase allowing the integration of the transgene. The principal drawback is the lasting presence of the transposase, which could remobilize the transgene once it has been inserted. Our study focused on the pharmacokinetics of the transposition process mediated by the piggyBac transposase mRNA transfection. Exogenous mRNA internalization and trafficking were investigated towards a better apprehension and fine control of the piggyBac transposase bioavailability. RESULTS: The mRNA prototype designed in this study provides a very narrow expression window of transposase, which allows high efficiency transposition with no cytotoxicity. Our data reveal that exogenous transposase mRNA enters cells by clathrin and caveolae-mediated endocytosis, before finishing in late endosomes 3 h after transfection. At this point, the mRNA is dissociated from its carrier and localized in stress granules, but not in cytoplasmic processing bodies. Some weaker signals have been observed in stress granules at 18 h and 48 h without causing prolonged production of the transposase. So, we designed an mRNA that is efficiently translated with a peak of transposase production 18 h post-transfection without additional release of the molecule. This confines the integration of the transgene in a very small time window. CONCLUSION: Our results shed light on processes of exogenous mRNA trafficking, which are crucial to estimate the mRNA bioavailability, and increase the biosafety of transgene integration mediated by transposition. This approach provides a new way for limiting the transgene copy in the genome and their remobilization by mRNA engineering and trafficking.

Introducing systematic dispatcher-assisted cardiopulmonary resuscitation (telephone-CPR) in a non-Advanced Medical Priority Dispatch System (AMPDS): implementation process and costs.

OBJECTIVE: In order to improve the quality of our Emergency Medical Services (EMS), to raise bystander cardiopulmonary resuscitation rates and thereby meet what is becoming a universal standard in terms of quality of emergency services, we decided to implement systematic dispatcher-assisted or telephone-CPR (T-CPR) in our medical dispatch center, a non-Advanced Medical Priority Dispatch System. The aim of this article is to describe the implementation process, costs and results following the introduction of this new "quality" procedure. METHODS: This was a prospective study. Over an 8-week period, our EMS dispatchers were given new procedures to provide T-CPR. We then collected data on all non-traumatic cardiac arrests within our state (Vaud, Switzerland) for the following 12months. For each event, the dispatchers had to record in writing the reason they either ruled out cardiac arrest (CA) or did not propose T-CPR in the event they did suspect CA. All emergency call recordings were reviewed by the medical director of the EMS. The analysis of the recordings and the dispatchers' written explanations were then compared. RESULTS: During the 12-month study period, a total of 497 patients (both adults and children) were identified as having a non-traumatic cardiac arrest. Out of this total, 203 cases were excluded and 294 cases were eligible for T-CPR. Out of these eligible cases, dispatchers proposed T-CPR on 202 occasions (or 69% of eligible cases). They also erroneously proposed T-CPR on 17 occasions when a CA was wrongly identified (false positive). This represents 7.8% of all T-CPR. No costs were incurred to implement our study protocol and procedures. CONCLUSIONS: This study demonstrates it is possible, using a brief campaign of sensitization but without any specific training, to implement systematic dispatcher-assisted cardiopulmonary resuscitation in a non-Advanced Medical Priority Dispatch System such as our EMS that had no prior experience with systematic T-CPR. The results in terms of T-CPR delivery rate and false positive are similar to those found in previous studies. We found our results satisfying the given short time frame of this study. Our results demonstrate that it is possible to improve the quality of emergency services at moderate or even no additional costs and this should be of interest to all EMS that do not presently benefit from using T-CPR procedures. EMS that currently do not offer T-CPR should consider implementing this technique as soon as possible, and we expect our experience may provide answers to those planning to incorporate T-CPR in their daily practice.

A cell therapy approach for erythropoietin delivery using encapsulated human primary fibroblasts

Summary Cell therapy has emerged as a strategy for the treatment of various human diseases. Cells can be transplanted considering their morphological and functional properties to restore a tissue damage, as represented by blood transfusion, bone marrow or pancreatic islet cells transplantation. With the advent of the gene therapy, cells also were used as biological supports for the production of therapeutic molecules that can act either locally or at distance. This strategy represents the basis of ex vivo gene therapy characterized by the removal of cells from an organism, their genetic modification and their implantation into the same or another individual in a physiologically suitable location. The tissue or biological function damage dictates the type of cells chosen for implantation and the required function of the implanted cells. The general aim of this work was to develop an ex vivo gene therapy approach for the secretion of erythropoietin (Epo) in patients suffering from Epo-responsive anemia, thus extending to humans, studies previously performed with mouse cells transplanted in mice and rats. Considering the potential clinical application, allogeneic primary human cells were chosen for practical and safety reasons. In contrast to autologous cells, the use of allogeneic cells allows to characterize a cell lineage that can be further transplanted in many individuals. Furthermore allogeneic cells avoid the potential risk of zoonosis encountered with xenogeneic cells. Accordingly, the immune reaction against this allogeneic source was prevented by cell macro- encapsulation that prevents cell-to-cell contact with the host immune system and allows to easy retrieve the implanted device. The first step consisted in testing the survival of various human primary cells that were encapsulated and implanted for one month in the subcutaneous tissue of immunocompetent and naturally or therapeutically immunodepressed mice, assuming that xenogeneic applications constitute a stringent and representative screening before human transplantation. A fibroblast lineage from the foreskin of a young donor, DARC 3.1 cells, showed the highest mean survival score. We have then performed studies to optimize the manufacturing procedures of the encapsulation device for successful engraftment. The development of calcifications on the polyvinyl alcohol (PVA) matrix serving as a scaffold for enclosed cells into the hollow fiber devices was reported after one month in vivo. Various parameters, including matrix rinsing solutions, batches of PVA and cell lineages were assessed for their respective role in the development of the phenomenon. We observed that the calcifications could be totally prevented by using ultra-pure sterile water instead of phosphate buffer saline solution in the rinsing procedure of the PVA matrix. Moreover, a higher lactate dehydrogenase activity of the cells was found to decrease calcium depositions due to more acidic microenvironment, inhibiting the calcium precipitation. After the selection of the appropriate cell lineage and the optimization of encapsulation conditions, a retroviral-based approach was applied to DARC 3.1 fibroblasts for the transduction of the human Epo cDNA. Various modifications of the retroviral vector and the infection conditions were performed to obtain clinically relevant levels of human Epo. The insertion of a post-transcriptional regulatory element from the woodchuck hepatitis virus as well as of a Kozak consensus sequence led to a 7.5-fold increase in transgene expression. Human Epo production was further optimized by increasing the multiplicity of infection and by selecting high producer cells allowing to reach 200 IU hEpo/10E6 cells /day. These modified cells were encapsulated and implanted in vivo in the same conditions as previously described. All the mouse strains showed a sustained increase in their hematocrit and a high proportion of viable cells were observed after retrieval of the capsules. Finally, in the perspective of human application, a syngeneic model using encapsulated murine myoblasts transplanted in mice was realized to investigate the roles of both the host immune response and the cells metabolic requirements. Various loading densities and anti-inflammatory as well as immunosuppressive drugs were studied. The results showed that an immune process is responsible of cell death in capsules loaded at high cell density. A supporting matrix of PVA was shown to limit the cell density and to avoid early metabolic cell death, preventing therefore the immune reaction. This study has led to the development of encapsulated cells of human origin producing clinically relevant amounts of human EPO. This work resulted also to the optimization of cell encapsulation technical parameters allowing to begin a clinical application in end-stage renal failure patients. Résumé La thérapie cellulaire s'est imposée comme une stratégie de traitement potentiel pour diverses maladies. Si l'on considère leur morphologie et leur fonction, les cellules peuvent être transplantées dans le but de remplacer une perte tissulaire comme c'est le cas pour les transfusions sanguines ou les greffes de moelle osseuse ou de cellules pancréatiques. Avec le développement de la thérapie génique, les cellules sont également devenues des supports biologiques pour la production de molécules thérapeutiques. Cette stratégie représente le fondement de la thérapie génique ex vivo, caractérisée par le prélèvement de cellules d'un organisme, leur modification génétique et leur implantation dans le même individu ou dans un autre organisme. Le choix du type de cellule et la fonction qu'elle doit remplir pour un traitement spécifique dépend du tissu ou de la fonction biologique atteintes. Le but général de ce travail est de développer .une approche par thérapie génique ex vivo de sécrétion d'érythropoïétine (Epo) chez des patients souffrant d'anémie, prolongeant ainsi des travaux réalisés avec des cellules murines implantées chez des souris et des rats. Dans cette perpective, notre choix s'est porté sur des cellules humaines primaires allogéniques. En effet, contrairement aux cellules autologues, une caractérisation unique de cellules allogéniques peut déboucher sur de nombreuses applications. Par ailleurs, l'emploi de cellules allogéniques permet d'éviter les riques de zoonose que l'on peut rencontrer avec des cellules xénogéniques. Afin de protéger les cellules allogéniques soumises à une réaction immunitaire, leur confinement dans des macro-capsules cylindriques avant leur implantation permet d'éviter leur contact avec les cellules immunitaires de l'hôte, et de les retrouver sans difficulté en cas d'intolérance ou d'effet secondaire. Dans un premier temps, nous avons évalué la survie de différentes lignées cellulaires humaines primaires, une fois encapsulées et implantées dans le tissu sous-cutané de souris, soit immunocompétentes, soit immunodéprimées naturellement ou par l'intermédiaire d'un immunosuppresseur. Ce modèle in vivo correspond à des conditions xénogéniques et représente par conséquent un environnement de loin plus hostile pour les cellules qu'une transplantation allogénique. Une lignée fibroblastique issue du prépuce d'un jeune enfant, nommée DARC 3 .1, a montré une remarquable résistance avec un score de survie moyen le plus élevé parmi les lignées testées. Par la suite, nous nous sommes intéressés aux paramètres intervenant dans la réalisation du système d'implantation afin d'optimaliser les conditions pour une meilleure adaptation des cellules à ce nouvel environnement. En effet, en raison de l'apparition, après un mois in vivo, de calcifications au niveau de la matrice de polyvinyl alcohol (PVA) servant de support aux cellules encapsulées, différents paramètres ont été étudiés, tels que les procédures de fabrication, les lots de PVA ou encore les lignées cellulaires encapsulées, afin de mettre en évidence leur rôle respectif dans la survenue de ce processus. Nous avons montré que l'apparition des calcifications peut être totalement prévenue par l'utilisation d'eau pure au lieu de tampon phosphaté lors du rinçage des matrices de PVA. De plus, nous avons observe qu'un taux de lactate déshydrogénase cellulaire élevé était corrélé avec une diminution des dépôts de calcium au sein de la matrice en raison d'un micro-environnement plus acide inhibant la précipitation du calcium. Après sélection de la lignée cellulaire appropriée et de l'optimisation des conditions d'encapsulation, une modification génétique des fibroblastes DARC 3.1 a été réalisée par une approche rétrovirale, permettant l'insertion de l'ADN du gène de l'Epo dans le génome cellulaire. Diverses modifications, tant au niveau génétique qu'au niveau des conditions d'infection, ont été entreprises afin d'obtenir des taux de sécrétion d'Epo cliniquement appropriés. L'insertion dans la séquence d'ADN d'un élément de régulation post¬transcriptionnelle dérivé du virus de l'hépatite du rongeur (« woodchuck ») ainsi que d'une séquence consensus appelée « Kozak » ont abouti à une augmentation de sécrétion d'Epo 7.5 fois plus importante. De même, l'optimisation de la multiplicité d'infection et la sélection plus drastique des cellules hautement productrices ont permis finalement d'obtenir une sécrétion correspondant à 200 IU d'Epo/10E6 cells/jour. Ces cellules génétiquement modifiées ont été encapsulées et implantées in vivo dans les mêmes conditions que celles décrites plus haut. Toutes les souris transplantées ont montré une augmentation significative de leur hématocrite et une proportion importante de cellules présentait une survie conservée au moment de l'explantation des capsules. Finalement, dans la perspective d'une application humaine, un modèle syngénique a été proposé, basé sur l'implantation de myoblastes murins encapsulés dans des souris, afin d'investiguer les rôles respectifs de la réponse immunitaire du receveur et des besoins métaboliques cellulaires sur leur survie à long terme. Les cellules ont été encapsulées à différentes densités et les animaux transplantés se sont vus administrer des injections de molécules anti-inflammatoires ou immunosuppressives. Les résultats ont démontré qu'une réaction immunologique péri-capsulaire était à la base du rejet cellulaire dans le cas de capsules à haute densité cellulaire. Une matrice de PVA peut limiter cette densité et éviter une mort cellulaire précoce due à une insuffisance métabolique et par conséquent prévenir la réaction immunitaire. Ce travail a permis le développement de cellules encapsulées d'origine humaine sécrétant des taux d'Epo humaine adaptés à des traitements cliniques. De pair avec l'optimalisation des paramètres d'encapsulation, ces résultats ont abouti à l'initiation d'une application clinique destinée à des patients en insuffisance rénale terminale.

Budgeting rockfall and modeling sedimentary delivery in torrent systems

This thesis is a compilation of projects to study sediment processes recharging debris flow channels. These works, conducted during my stay at the University of Lausanne, focus in the geological and morphological implications of torrent catchments to characterize debris supply, a fundamental element to predict debris flows. Other aspects of sediment dynamics are considered, e.g. the coupling headwaters - torrent, as well as the development of a modeling software that simulates sediment transfer in torrent systems. The sediment activity at Manival, an active torrent system of the northern French Alps, was investigated using terrestrial laser scanning and supplemented with geostructural investigations and a survey of sediment transferred in the main torrent. A full year of sediment flux could be observed, which coincided with two debris flows and several bedload transport events. This study revealed that both debris flows generated in the torrent and were preceded in time by recharge of material from the headwaters. Debris production occurred mostly during winter - early spring time and was caused by large slope failures. Sediment transfers were more puzzling, occurring almost exclusively in early spring subordinated to runoffconditions and in autumn during long rainfall. Intense rainstorms in summer did not affect debris storage that seems to rely on the stability of debris deposits. The morpho-geological implication in debris supply was evaluated using DEM and field surveys. A slope angle-based classification of topography could characterize the mode of debris production and transfer. A slope stability analysis derived from the structures in rock mass could assess susceptibility to failure. The modeled rockfall source areas included more than 97% of the recorded events and the sediment budgets appeared to be correlated to the density of potential slope failure. This work showed that the analysis of process-related terrain morphology and of susceptibility to slope failure document the sediment dynamics to quantitatively assess erosion zones leading to debris flow activity. The development of erosional landforms was evaluated by analyzing their geometry with the orientations of potential rock slope failure and with the direction of the maximum joint frequency. Structure in rock mass, but in particular wedge failure and the dominant discontinuities, appear as a first-order control of erosional mechanisms affecting bedrock- dominated catchment. They represent some weaknesses that are exploited primarily by mass wasting processes and erosion, promoting not only the initiation of rock couloirs and gullies, but also their propagation. Incorporating the geological control in geomorphic processes contributes to better understand the landscape evolution of active catchments. A sediment flux algorithm was implemented in a sediment cascade model that discretizes the torrent catchment in channel reaches and individual process-response systems. Each conceptual element includes in simple manner geomorphological and sediment flux information derived from GIS complemented with field mapping. This tool enables to simulate sediment transfers in channels considering evolving debris supply and conveyance, and helps reducing the uncertainty inherent to sediment budget prediction in torrent systems. Cette thèse est un recueil de projets d'études des processus de recharges sédimentaires des chenaux torrentiels. Ces travaux, réalisés lorsque j'étais employé à l'Université de Lausanne, se concentrent sur les implications géologiques et morphologiques des bassins dans l'apport de sédiments, élément fondamental dans la prédiction de laves torrentielles. D'autres aspects de dynamique sédimentaire ont été abordés, p. ex. le couplage torrent - bassin, ainsi qu'un modèle de simulation du transfert sédimentaire en milieu torrentiel. L'activité sédimentaire du Manival, un système torrentiel actif des Alpes françaises, a été étudiée par relevés au laser scanner terrestre et complétée par une étude géostructurale ainsi qu'un suivi du transfert en sédiments du torrent. Une année de flux sédimentaire a pu être observée, coïncidant avec deux laves torrentielles et plusieurs phénomènes de charriages. Cette étude a révélé que les laves s'étaient générées dans le torrent et étaient précédées par une recharge de débris depuis les versants. La production de débris s'est passée principalement en l'hiver - début du printemps, causée par de grandes ruptures de pentes. Le transfert était plus étrange, se produisant presque exclusivement au début du printemps subordonné aux conditions d'écoulement et en automne lors de longues pluies. Les orages d'été n'affectèrent guère les dépôts, qui semblent dépendre de leur stabilité. Les implications morpho-géologiques dans l'apport sédimentaire ont été évaluées à l'aide de MNT et études de terrain. Une classification de la topographie basée sur la pente a permis de charactériser le mode de production et transfert. Une analyse de stabilité de pente à partir des structures de roches a permis d'estimer la susceptibilité à la rupture. Les zones sources modélisées comprennent plus de 97% des chutes de blocs observées et les bilans sédimentaires sont corrélés à la densité de ruptures potentielles. Ce travail d'analyses des morphologies du terrain et de susceptibilité à la rupture documente la dynamique sédimentaire pour l'estimation quantitative des zones érosives induisant l'activité torrentielle. Le développement des formes d'érosion a été évalué par l'analyse de leur géométrie avec celle des ruptures potentielles et avec la direction de la fréquence maximale des joints. Les structures de roches, mais en particulier les dièdres et les discontinuités dominantes, semblent être très influents dans les mécanismes d'érosion affectant les bassins rocheux. Ils représentent des zones de faiblesse exploitées en priorité par les processus de démantèlement et d'érosion, encourageant l'initiation de ravines et couloirs, mais aussi leur propagation. L'incorporation du control géologique dans les processus de surface contribue à une meilleure compréhension de l'évolution topographique de bassins actifs. Un algorithme de flux sédimentaire a été implémenté dans un modèle en cascade, lequel divise le bassin en biefs et en systèmes individuels répondant aux processus. Chaque unité inclut de façon simple les informations géomorpologiques et celles du flux sédimentaire dérivées à partir de SIG et de cartographie de terrain. Cet outil permet la simulation des transferts de masse dans les chenaux, considérants la variabilité de l'apport et son transport, et aide à réduire l'incertitude liée à la prédiction de bilans sédimentaires torrentiels. Ce travail vise très humblement d'éclairer quelques aspects de la dynamique sédimentaire en milieu torrentiel.

Nanoparticles for gene delivery to retinal pigment epithelial cells.

PURPOSE: To evaluate the safety and potential use of poly(lactic) acid (PLA) and poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) as vectors for gene transfer to RPE cells. METHODS: Experiments were conducted with primary bovine RPE cells and with the ARPE-19 human RPE cell line. Rhodamine loaded NPs were used to study factors influencing the internalization process by the various RPE cells: concentrations of NPs, duration of contact time, stage of cell culture and ambient temperature. The extent of NPs internalization was evaluated by fluorescence and phase microscopy. Potential NP toxicity was measured by the trypan blue exclusion dye test and the MTT method. Green fluorescent protein (GFP) plasmid or red nuclear fluorescent protein (RNFP) plasmid were sequestered in NPs. The ability ot these "loaded" NPs to generate gene transfection and protein expression in RPE cells was assessed both in vivo and in vitro by fluorescence and confocal microscopy. RESULTS: The extent of NP internalization in cultured cells increases with their concentration reaching a plateau at 1 mg/ml and a contact time of up to 6 h. Temperature and culture stage did not influence the in vitro internalization process. No toxic effects on RPE cells could be detected when these were incubated with up to 4 mg/ml of NPs. In human and bovine RPE cells incubated with GFP loaded NPs, cytoplasmic green fluorescence was observed in 14+/-1.65% of the cultured cells. Incubation with RNFP loaded NPs yielded a nuclear red fluorescence in 18.9+/-1.6% of the cells. These percentage levels of expression initially detected after 48 h of incubation remained unchanged during the following 8 additional days in culture. No significant differences in the extent of cytoplasm or nuclear fluorescence expression were observed between bovine or human RPE cultured cells. In vivo, a preferential RNFP expression within the RPE cell layer was detected after intra vitreous injection of RNFP plasmid loaded NPs. CONCLUSIONS: The ability of PLGA NPs to sequester plasmids, their nontoxic characteristics, and rapid internalization enables gene transfer and expression in RPE cells. These findings may be of potential use when designing future gene therapy strategies for ocular diseases of the posterior segment.

Performance measurement oforder-delivery chain in SMEs: Case study

Tutkimus pyrkii selvittämään, kuinka tehokas suorituskykymittaristo voidaan parhaiten suunnitella pk-yrityksessä. Tutkimuksen tavoitteena on luoda suorituskykymittaristo pienen kohdeyrityksen johtajien tarpeisiin. Päähuomion kohteena on yrityksen tilaus-toimitusketju ja arvoverkko. Työ on luonteeltaan kvalitatiivinen toimintatutkimus, joka noudattaa toiminta-analyyttista tutkimusotetta. Työn teoriaosassa selvitetään, kuinka suorituskyvyn mittaaminen sekä materiaali-, tieto- ja rahavirtojen hallinta on kehittynyt viime vuosina pk-yrityksen näkökulmasta. Mittariston suunnittelu aloitetaan kohdeyrityksen perusteellisella analyysilla. Tämän pohjalta määritellään yrityksen kriittiset menestystekijät, joista lopulta johdetaan suorituskykymittarit. Tutkimuksen perusteella voidaan todeta, että yleinen asenne mittaamista kohtaan, strategian huomioinnin puute sekä tietojärjestelmien rajoitteet ovat päähaasteita pk-yrityksen suorituskyvyn mittaamisessa. Mittareiden tuleekin olla melko yksinkertaisia ja helppoja käyttää, jotta mittaamisen ei koettaisi kuluttavan rajallisia resursseja liikaa. Mittariston tulee kuitenkin antaa kokonaisvaltainen kuva yrityksen suorituskyvystä, johon vaikuttavat kaikki arvoverkon osapuolet ja heidän yhteistyö toistensa kanssa.

Transfer pricing tool development process based on valve package production costs

Tämän diplomityön päätavoitteena oli parantaa kehitetyn kustannusperusteisen siirtohinnoittelutyökalun ominaisuuksia osastokohtaisen kustannusarviointiprosessin käyttöön. Työ on vaikeutunut lähimenneisyyden heikosta hintakyselyiden vastauskyvystä. Työn pääongelmana oli kerätä luotettavaa tuotannonohjausjärjestelmän kustannusaineistoa osittain vanhentuneista vakioventtiilien koneistus- ja materiaalitiedosta. Tutkimuksessa käytetyt tärkeimmät tutkimusmenetelmät voidaan jakaa siirtohinnoittelu- ja kustannusarvioprosessien kirjallisuustutkimukseen, kenttäanalyysiin ja nykyisen Microsoft Excel –siirtohinnoittelutyökalun kehittämiseen eri osastojen rajapinnassa. Siirtohinnoittelumenetelmät ovat yleisesti jaettu kustannus-, markkina- ja neuvotteluperusteisiin malleihin, jotka harvoin sellaisenaan kohtaavat siirtohinnoittelulle asetetut tavoitteet. Tämä ratkaisutapa voi johtaa tilanteisiin, jossa kaksi erillistä menetelmää sulautuvat yhteen. Lisäksi varsinaiseen siirtohinnoittelujärjestelmään yleensä vaikuttavat useat sisäiset ja ulkoiset tekijät. Lopullinen siirtohinnoittelumenetelmä tulisi ehdottomasti tukea myös yrityksen visiota ja muita liiketoiminnalle asetettuja strategioita. Työn tuloksena saatiin laajennettu Microsoft Excel –sovellus, joka vaatii sekä vuosittaista että kuukausittaista erikoisventtiilimateriaalien hinta- ja toimitusaikatietojen päivittämistä. Tämä ratkaisutapa ehdottomasti parantaa kustannusarviointiprosessia, koska myös alihankkijatietoja joudutaan tutkimaan systemaattisesti. Tämän jälkeen koko siirtohinnoitteluprosessia voidaan kehittää muuntamalla kokoonpano- ja testaustyövaiheiden kustannusrakennetta toimintoperustaisen kustannuslaskentamallin mukaiseksi.

Wireless Applications Evaluation and Development Process: Case -Paper Industry Logistics

Sähköisen liiketoiminnan ja mobiliteetin konvergenssi yhdessä teknologisen innovaation kiihtyvän vauhdin kanssa ovat saaneet aikaan kiinnostusta langattomia liiketoimintaratkaisuja kohtaan. Tämän diplomityön tavoitteena oli tutkia sähköisen liiketoiminnan langattomien sovellusten arviointi- ja kehitysprosessia. Työ keskittyy tarkastelemaan paperiteollisuuden toimitusketjun langatonta seurantaa. Tutkimuksessa esitetään langattoman sähköisen liiketoiminnan määritelmä, kuvaillaan langattomuuden eri sovellusalueita ja sovellusten arviointi- ja kehitysprosessin strategisia sekä teknologisia ulottuvuuksia. Työ luo viitekehyksen, jonka avulla tarkastella langattomien teknologioiden merkitystä logistiikassa. Tutkimuksen merkittävin tulos on prosessimalli sovellusten arvioimiseksi ja kehittämiseksi. Mallilla kehitetty langaton sovellus osoittautui tarkastelussa hyödylliseksi toimitusketjun hallinnassa.

Improving the order-delivery chain

Tutkielman tavoitteena on tarkastella letkuventtiilien tilaus-toimitusketjua ja selvittää, kuinka se muodostuu. Tavoitteena on laatia selvitys yrityksen tilaus-toimitusketjun muodostumisen vaiheista yrityksen sisäiseen käyttöön ja tutkia, kuinka ketjua voitaisiin parantaa, jotta tulevaisuudessa asiakkaita voitaisiin palvella paremmin ja joustavammin. Tutkimusongelmaa lähestytään prosessiajattelun näkökulmasta ja tutkielmassa käytetään kvalitatiivista tutkimusmenetelmää, jonka pääasiallisena tiedonkeruuvälineenä on vapaamuotoiset haastattelut, yrityksen dokumenttien tutkiminen ja analysointi sekä yrityksen toiminnan havainnointi. Tilaus-toimitusketjun parantaminen edellyttää yritykseltä ja sen edustajilta asiakkaiden ostokäyttäytymisen ohjaamista, tiedon avointa ja oikea-aikaista jakamista kaikille sitä tarvitseville sekä kulttuurierojen huomioon ottamista. Erityisesti tilaus-toimitusketjun alkuvaiheisiin tulisi panostaa tulevaisuudessa, sillä monet ongelmat syntyvät tutkimuksen mukaan toimitusketjun alkupuolella.

Imaging techniques applied for detection of secretion, transgene delivery and G proteincoupled receptors in reproductive and endocrine cells in vivo and in vitro

Post-testicular sperm maturation occurs in the epididymis. The ion concentration and proteins secreted into the epididymal lumen, together with testicular factors, are believed to be responsible for the maturation of spermatozoa. Disruption of the maturation of spermatozoa in the epididymis provides a promising strategy for generating a male contraceptive. However, little is known about the proteins involved. For drug development, it is also essential to have tools to study the function of these proteins in vitro. One approach for screening novel targets is to study the secretory products of the epididymis or the G protein-coupled receptors (GPCRs) that are involved in the maturation process of the spermatozoa. The modified Ca2+ imaging technique to monitor release from PC12 pheochromocytoma cells can also be applied to monitor secretory products involved in the maturational processes of spermatozoa. PC12 pheochromocytoma cells were chosen for evaluation of this technique as they release catecholamines from their cell body, thus behaving like endocrine secretory cells. The results of the study demonstrate that depolarisation of nerve growth factor -differentiated PC12 cells releases factors which activate nearby randomly distributed HEL erythroleukemia cells. Thus, during the release process, the ligands reach concentrations high enough to activate receptors even in cells some distance from the release site. This suggests that communication between randomly dispersed cells is possible even if the actual quantities of transmitter released are extremely small. The development of a novel method to analyse GPCR-dependent Ca2+ signalling in living slices of mouse caput epididymis is an additional tool for screening for drug targets. By this technique it was possible to analyse functional GPCRs in the epithelial cells of the ductus epididymis. The results revealed that, both P2X- and P2Y-type purinergic receptors are responsible for the rapid and transient Ca2+ signal detected in the epithelial cells of caput epididymides. Immunohistochemical and reverse transcriptase-polymerase chain reaction (RTPCR) analyses showed the expression of at least P2X1, P2X2, P2X4 and P2X7, and P2Y1 and P2Y2 receptors in the epididymis. Searching for epididymis-specific promoters for transgene delivery into the epididymis is of key importance for the development of specific models for drug development. We used EGFP as the reporter gene to identify proper promoters to deliver transgenes into the epithelial cells of the mouse epididymis in vivo. Our results revealed that the 5.0 kb murine Glutathione peroxidase 5 (GPX5) promoter can be used to target transgene expression into the epididymis while the 3.8 kb Cysteine-rich secretory protein-1 (CRISP-1) promoter can be used to target transgene expression into the testis. Although the visualisation of EGFP in living cells in culture usually poses few problems, the detection of EGFP in tissue sections can be more difficult because soluble EGFP molecules can be lost if the cell membrane is damaged by freezing, sectioning, or permeabilisation. Furthermore, the fluorescence of EGFP is dependent on its conformation. Therefore, fixation protocols that immobilise EGFP may also destroy its usefulness as a fluorescent reporter. We therefore developed a novel tissue preparation and preservation techniques for EGFP. In addition, fluorescence spectrophotometry with epididymal epithelial cells in suspension revealed the expression of functional purinergic, adrenergic, cholinergic and bradykinin receptors in these cell lines (mE-Cap27 and mE-Cap28). In conclusion, we developed new tools for studying the role of the epididymis in sperm maturation. We developed a new technique to analyse GPCR dependent Ca2+ signalling in living slices of mouse caput epididymis. In addition, we improved the method of detecting reporter gene expression. Furthermore, we characterised two epididymis-specific gene promoters, analysed the expression of GPCRs in epididymal epithelial cells and developed a novel technique for measurement of secretion from cells.

Satisfaction with pregnancy and delivery services: The quality of maternity care services as experienced by women

Objective: The objective of this study was to investigate the opinions of women regarding the satisfaction about the quality of maternity care received. We hope to establish whether health care technology increases satisfaction or whether it actually interferes with the construction of personal satisfaction in the process of care. Design and setting: Information was gathered using the focus group technique. The area of study comprised the post-natal groups run as part of the Sexual and Reproductive Health Programme of the Catalan Health Authority. (Spain) Participants: Five focus groups were held between May 2006 and July 2007. Findings: Quality of care is a complex concept in which a number of independent core features can be identified. We have grouped these core features into three basic categories. Safety: the hospital and its technological facilities, and the technical expertise of health professionals. The other two main pillars of quality of care are the human dimension of the relationship between the carers and the patient, and finally the structural aspects that determine the context in which the heath care is provided. Key conclusions and implications for practice: The mothers of our study feel satisfied with healthcare technology and view it as a source of security; technology become indispensable features in order to reduce the anxiety provoked by the perceived lack of confidence in their ability as mothers. In this study, women, both during pregnancy and especially when giving birth, believe their feelings and values should be understood by professionals, from whom they seek empathy and a personal commitment, and not just information.

Satisfaction with pregnancy and delivery services: The quality of maternity care services as experienced by women

Objective: The objective of this study was to investigate the opinions of women regarding the satisfaction about the quality of maternity care received. We hope to establish whether health care technology increases satisfaction or whether it actually interferes with the construction of personal satisfaction in the process of care. Design and setting: Information was gathered using the focus group technique. The area of study comprised the post-natal groups run as part of the Sexual and Reproductive Health Programme of the Catalan Health Authority. (Spain) Participants: Five focus groups were held between May 2006 and July 2007. Findings: Quality of care is a complex concept in which a number of independent core features can be identified. We have grouped these core features into three basic categories. Safety: the hospital and its technological facilities, and the technical expertise of health professionals. The other two main pillars of quality of care are the human dimension of the relationship between the carers and the patient, and finally the structural aspects that determine the context in which the heath care is provided. Key conclusions and implications for practice: The mothers of our study feel satisfied with healthcare technology and view it as a source of security; technology become indispensable features in order to reduce the anxiety provoked by the perceived lack of confidence in their ability as mothers. In this study, women, both during pregnancy and especially when giving birth, believe their feelings and values should be understood by professionals, from whom they seek empathy and a personal commitment, and not just information.

Interactions of chitosan/genipin hydrogels during drug delivery: a QSPR approach

A hydrogel comprised of chitosan crosslinked using the low-toxicity crosslinker genipin was prepared, and the absorption of glibenclamide by the hydrogel was investigated. Optimized structures and their molecular electrostatic potentials were calculated using the AM1 method, and the results were used to evaluate the molecular interactions between the three compounds. The quantitative structure-property relationship model was also used to estimate the activity of the chemicals on the basis their molecular structures. In addition, theoretical Fourier transform infrared spectra were calculated to analyze the intermolecular interactions in the proposed system. Finally, the hydrophilicity of the hydrogel and its influence on the absorption process were also estimated.