A single epidermal stem cell strategy for safe ex vivo gene therapy.

There is a widespread agreement from patient and professional organisations alike that the safety of stem cell therapeutics is of paramount importance, particularly for ex vivo autologous gene therapy. Yet current technology makes it difficult to thoroughly evaluate the behaviour of genetically corrected stem cells before they are transplanted. To address this, we have developed a strategy that permits transplantation of a clonal population of genetically corrected autologous stem cells that meet stringent selection criteria and the principle of precaution. As a proof of concept, we have stably transduced epidermal stem cells (holoclones) obtained from a patient suffering from recessive dystrophic epidermolysis bullosa. Holoclones were infected with self-inactivating retroviruses bearing a COL7A1 cDNA and cloned before the progeny of individual stem cells were characterised using a number of criteria. Clonal analysis revealed a great deal of heterogeneity among transduced stem cells in their capacity to produce functional type VII collagen (COLVII). Selected transduced stem cells transplanted onto immunodeficient mice regenerated a non-blistering epidermis for months and produced a functional COLVII. Safety was assessed by determining the sites of proviral integration, rearrangements and hit genes and by whole-genome sequencing. The progeny of the selected stem cells also had a diploid karyotype, was not tumorigenic and did not disseminate after long-term transplantation onto immunodeficient mice. In conclusion, a clonal strategy is a powerful and efficient means of by-passing the heterogeneity of a transduced stem cell population. It guarantees a safe and homogenous medicinal product, fulfilling the principle of precaution and the requirements of regulatory affairs. Furthermore, a clonal strategy makes it possible to envision exciting gene-editing technologies like zinc finger nucleases, TALENs and homologous recombination for next-generation gene therapy.

Un fòssil juràssic amb un nom popular peculiar a la Vall de Sóller

En aquest treball s’estudia, des d’una perspectiva etnopaleontològica, la denominació popular aplicada pels habitants de la Vall de Sóller al braquiòpode fòssil Terabratula davidsoni Haime 1855, fòssil del període Juràssic, descrit pel geòleg francès Jules Haime al segle XIX al jaciment de Muleta de ca s’Hereu i que apareix a diversos indrets de la zona de Sóller. També es fa una revisió de l’estat actual del coneixement sobre la presència d’aquest fòssil a l’illa de Mallorca, a la vegada que se’n proposa una revisió taxonòmica.

Go-to-market strategy with pharmacies

The purpose of the research is to develop a go-to-market strategy with pharmacies. As it was agreed with the client of the study, Reckitt Benckiser, the focus is solely on non-prescription products. Therefore, prescription medicines are not considered in the study. The main objective of the research is to clarify consumer and pharmacy personnel behavior concerning non-prescription products. These issues are observed with surveys, which are provided to consumers and pharmacy personnel. The go-to-market strategy is based on the survey results and is comprised by utilizing the marketing-mix model. Legislation and the present state & trends are additional minor research problems of the study. The results of the research provide many descriptive insights about consumer and pharmacy personnel behavior. It is concluded that the consumers’ level of involvement with non-prescription products is low and the type of behavior is habitual. It is also demonstrated that several decision-making criteria are very different among different age groups and genders. Concerning pharmacy personnel, the factors that they base their product recommendations are revealed. In addition, the sources of medicine information for both consumers and pharmacy personnel are found out.

Marketing strategy for a GSM phone service. Target market, St. Petersburg Russia. Case MegaFon

Tämä pro gradu tutkielma esittää markkinointistrategian digitaaliselle matkapuhelinpalvelulle penetroiduttaessa uusille markkinoille. MegaFon on uuden sukupolven mobiilioperaattori, jolla on lukuisia teknlogiaan perustuvia etuisuuksia puolellaan. Markkinointistrategian perusteena asiakkaat on määritelty, paikallistettu ja analysoitu. Tämän lisäksi, palvelun positiointi, hinnoittelu- ja jakelukanavavaihtoehdot on myöskin analysoitu ja määritelty. Menestystekijöihin liittyvät kysymykset, myynnin jälkeiseen toimintaan liittyvät asiat on myös tutkittu. Teoreettiset aspektit liittyvät pääsääntöisesti uuden palvelun ja palveluiden lanseeramiseen (palvelu, palvelun elinkaariajattelu), niiden markkinointistrategioihin lanseerausvaiheessa ja markkinointikanavien päättämiseen. Tutkimuksessa on selitetty MegaFonin ennustamis- ja lähestymistavat, joilla on valotettu todellista markkinatilannetta. Tämän tutkielman informaatio on kerätty useista lähteistä, kuten: yleistä aiheeseen liittyvää kirjallisuutta, sisäisiä raportteja ja Megafonin materiaalia, yhteistyökumppaneiden aineistoa, Internettia ja muuta saatavilla olevaa materiaalia. Tuloksena on määritelty päätöksenteon avainkohdat ja osaltaan perinteiset lähestymistavat on kyseenalaistettu.

Customization, transparency and proximity: a user- centered content strategy applied to the design of a virtual library website

We present a case study of the redesign of the organizational presentation and content of the Virtual Library website at the Universitat Oberta de Catalunya (Open University of Catalonia, UOC), based on a user-centered design strategy. The aim of the redesign was to provide users with more intuitive, usable and understandable content (textual content, resources and services) by implementing criteria of customization, transparency and proximity. The study also presents a selection of best practices for applying these criteria to the design of other library websites.

Towards an alternative testing strategy for nanomaterials used in nanomedicine: Lessons from NanoTEST.

In spite of recent advances in describing the health outcomes of exposure to nanoparticles (NPs), it still remains unclear how exactly NPs interact with their cellular targets. Size, surface, mass, geometry, and composition may all play a beneficial role as well as causing toxicity. Concerns of scientists, politicians and the public about potential health hazards associated with NPs need to be answered. With the variety of exposure routes available, there is potential for NPs to reach every organ in the body but we know little about the impact this might have. The main objective of the FP7 NanoTEST project ( www.nanotest-fp7.eu ) was a better understanding of mechanisms of interactions of NPs employed in nanomedicine with cells, tissues and organs and to address critical issues relating to toxicity testing especially with respect to alternatives to tests on animals. Here we describe an approach towards alternative testing strategies for hazard and risk assessment of nanomaterials, highlighting the adaptation of standard methods demanded by the special physicochemical features of nanomaterials and bioavailability studies. The work has assessed a broad range of toxicity tests, cell models and NP types and concentrations taking into account the inherent impact of NP properties and the effects of changes in experimental conditions using well-characterized NPs. The results of the studies have been used to generate recommendations for a suitable and robust testing strategy which can be applied to new medical NPs as they are developed.

El gest nostre de cada dia. La gestualitat emblemàtica com a patrimoni de la cultura popular

El libro de Lluís Payrató, El gest nostre de cada dia, es un estudio escrito en catalán de los gestos de la categoría de emblemas de la cultura catalana. Los emblemas constituyen un recurso comunicativo autónomo de la palabra, en el sentido de que expresan un mensaje que equivale a una palabra o expresión. El autor incorpora a la investigación el repertorio gestual que elaboró Joan Amades en 1957. La tesis central de la obra es la naturaleza cultural y contextual de los emblemas, de modo que pueden tener un significado mundial en algunos casos y un significado local en otros. La contribución del ensayo es una descripción de los gestos según su función comunicativa y la confección de un repertorio de 108 emblemas catalanes. El gest nostre de cada dia [Our daily gesture] is a study written by Lluís Payrató in Catalan about the Catalan culture. It deals with a type of gestures called emblems. The emblems are gestures that correspond to a word or expression. The author analyzes the gestural repertoire that developed in 1957 Joan Amades. The central thesis of the work is the cultural and contextual nature of the emblems, so that may have global significance in some cases and in other local significance. The contribution of the paper is a description of gestures by communicative function and the production of a repertoire of 108 Catalan emblems.

European employment strategy and spanish labour market policies

The paper aim is to analyse the influence of the European Employment Strategy (EES)in the implementation of the Spanish labour market policies. The first part of the paper describes the evolution and content of the EES. In the second one, the definition of activation is also explained. In addition to that, the ways how the EES develops and promotes active labour market policies are examined. The evolution of labour market policies in Spain and the current configuration of both active and passive policies are studied in the next three chapters. In these parts, the paper investigates to which extent the provisions of the EES have been implemented in Spain. The paper shows that: i) activation has been rising in the European countries since the implementation of the EES; ii) this fact has also happened in relative terms (comparing the evolution of active to passive policies); iii) Spain has been one of the countries which has led these processes; iv) the EES seems to have been influencing

Implementation of Customer Relationship Management Strategy in Pulp Company

Työn tarkoituksena oli löytää Asiakkuuksienhallintastrategian käyttöönoton ongelmakohtia asiakkuuksienhallintaan erikoistuneen konsulttiyrityksen asiakasyrityksen taholta. Lisäksi työssä etsitään ratkaisuja asiakkuusteorian viemiseksi käytäntöön. Työn anti on asiakkuusstrategian käytäntöön panon ongelmakohtien paikallistaminen, prosessin vaiheiden kuvaaminen sekä asiakkuuksienhallinnan tutkiminen lähtökohtana asiakkaalle tuotettu arvo. Asiakkuusstrategian implementoinnin ongelmakohtien ja kriittisten menestystekijöiden kuvaus ja vertailu käsitellään empiirisessä osassa suhteuttaen teoriaosuuden materiaaliin. CRM Group:n kannalta työ mahdollistaa osaltaan asiakasprojektien kehitystyön.Kirjallisuusosan pohjalta implementoinnin kannalta kriittisiksi menestystekijöiksi nousivat tietoteknisten ratkaisujen sulauttaminen osaksi asiakkuusstrategiaa tukevia toimintoja, aidon synergian löytäminen asiakas – toimittaja –suhteeseen sekä asiakkuusstrategiaa kehittävän organisaation sisäinen resursointi ja henkilöstön sitouttaminen.

Entry Strategy Issues in the Ophthalmic Industry: Entry Mode, Pricing and Distribution

Maahantulostrategia asettaa yrityksen kansainvälisiä liiketoimintoja ohjaavat tavoitteet, päämäärät, resurssit ja toiminnan suuntaviivat. Tämä diplomityö käsittelee yrityksen maahantulostrategian elementeistä operaatiomuodon valintaa, hinnoittelua ja jakelua. Työssä rakennetaan teoriakehys elementteihin liittyvien päätösten tutkimiseksi lääketeollisuuden ominaispiirteet huomioiden. Lääketeollisuudella on muihin teollisuudenaloihin verrattuna useita erityispiirteitä, joihin työ perehdyttää. Lisäksi työn olennainen osa on selvittää lääketeollisuuden maakohtaisia säädöksiä ja toimintamalleja. Diplomityö on tehty silmäläkkeitä valmistavalle, kehittävälle ja markkinoivalle Santen Oy:lle, joka suunnittelee toimintansa laajentamista Keski- ja Etelä-Euroopan markkinoille. Tässä laajentumisprosessissa ensimmäisenä kohdemaana on Saksa, jonka markkinoille suuntautuvia toimenpiteitä työ tutkii. Teoriakehyksen, markkinoiden ominaispiirteiden sekä useiden erilaisten analyysien pohjalta työn tavoitteena on antaa operaatiomuotoa, tuotteiden hinnoittelua ja jakelua koskevia suosituksia.

Optimizing the Anti-VEGF Treatment Strategy for Neovascular Age-Related Macular Degeneration: From Clinical Trials to Real-Life Requirements.

NlmCategory="UNASSIGNED">This Perspective discusses the pertinence of variable dosing regimens with anti-vascular endothelial growth factor (VEGF) for neovascular age-related macular degeneration (nAMD) with regard to real-life requirements. After the initial pivotal trials of anti-VEGF therapy, the variable dosing regimens pro re nata (PRN), Treat-and-Extend, and Observe-and-Plan, a recently introduced regimen, aimed to optimize the anti-VEGF treatment strategy for nAMD. The PRN regimen showed good visual results but requires monthly monitoring visits and can therefore be difficult to implement. Moreover, application of the PRN regimen revealed inferior results in real-life circumstances due to problems with resource allocation. The Treat-and-Extend regimen uses an interval based approach and has become widely accepted for its ease of preplanning and the reduced number of office visits required. The parallel development of the Observe-and-Plan regimen demonstrated that the future need for retreatment (interval) could be reliably predicted. Studies investigating the observe-and-plan regimen also showed that this could be used in individualized fixed treatment plans, allowing for dramatically reduced clinical burden and good outcomes, thus meeting the real life requirements. This progressive development of variable dosing regimens is a response to the real-life circumstances of limited human, technical, and financial resources. This includes an individualized treatment approach, optimization of the number of retreatments, a minimal number of monitoring visits, and ease of planning ahead. The Observe-and-Plan regimen achieves this goal with good functional results. Translational Relevance: This perspective reviews the process from the pivotal clinical trials to the development of treatment regimens which are adjusted to real life requirements. The article discusses this translational process which- although not the classical interpretation of translation from fundamental to clinical research, but a subsequent process after the pivotal clinical trials - represents an important translational step from the clinical proof of efficacy to optimization in terms of patients' and clinics' needs. The related scientific procedure includes the exploration of the concept, evaluation of security, and finally proof of efficacy.

Procurement, Quality and Productivity Enhancements and Manufacturing Strategy Formulation Applying Product Life Cycle Method

The objective of the thesis was to create a framework that can be used to define a manufacturing strategy taking advantage of the product life cycle method, which enables PQP enhancements. The starting point was to study synkron implementation of cost leadership and differentiation strategies in different stages of the life cycles. It was soon observed that Porter’s strategies were too generic for the complex and dynamic environment where customer needs deviate market and product specifically. Therefore, the strategy formulation process is based on the Terry Hill’s order-winner and qualifier concepts. The manufacturing strategy formulation is initiated with the definition of order-winning and qualifying criteria. From these criteria there can be shaped product specific proposals for action and production site specific key manufacturing tasks that they need to answer in order to meet customers and markets needs. As a future research it is suggested that the process of capturing order-winners and qualifiers should be developed so that the process would be simple and streamlined at Wallac Oy. In addition, defined strategy process should be integrated to the PerkinElmer’s SGS process. SGS (Strategic Goal Setting) is one of the PerkinElmer’s core management processes. Full Text: Null

The rare cancer network: ongoing studies and future strategy.

The Rare Cancer Network (RCN) was formed in the early 1990's to create a global network that could pool knowledge and resources in the studies of rare malignancies whose infrequency prevented both their study with prospective clinical trials. To date, the RCN has initiated 74 studies resulting in 46 peer reviewed publications. The First International Symposium of the Rare Cancer Network took place in Nice in March of 2014. Status updates and proposals for new studies were heard for fifteen topics. Ongoing studies continue for cardiac sarcomas, thyroid cancers, glomus tumors, and adult medulloblastomas. New proposals were presented at the symposium for primary hepatic lymphoma, solitary fibrous tumors, Rosai-Dorfman disease, tumors of the ampulla of Vater, salivary gland tumors, anorectal melanoma, midline nuclear protein in testes carcinoma, pulmonary lymphoepithelioma-like carcinoma, adenoid cystic carcinoma of the trachea, osteosarcomas of the mandible, and extra-cranial hemangiopericytoma. This manuscript presents the abstracts of those proposals and updates on ongoing studies, as well a brief summary of the vision and future of the RCN.

Customer expectation study in product development process and its role in strategy formulation

Tämä työ on tehty kansainväliselle metsäteollisuusyritykselle. Työn lähtökohtana oli tarve tutkia yrityksen mahdollisuuksia laajentaa toimintaansa uudelle markkinasegmentille, eläinruokapakkausmarkkinoille. Johtuen maailmanlaajuisesta eläinruoankulutuksen kasvusta, eläinruokapakkaukset ovat yritykselle mielenkiintoinen uusi markkina-alue. Onnistunut markkinoilletulo vaatii asiakastarpeiden ja -odotusten huomioimista tuotekehitys- ja markkinastrategian muodostamisessa. Tämän työn tavoitteena oli selvittää asiakkaiden odotuksia eläinruokapakkauksille, sekä mallintaa alalla vallitsevia ostoprosesseja. Asiakastarvetutkimus suunniteltiin perustuen kirjallisuuteen ja alustaviin markkina- ja asiakasanalyyseihin. Alustavat analyysit ovat tarpeellisia lähtötilanteen ja trendien selvittämiseksi. Itse tutkimus toteutettiin semi-konstruktoituna teemahaastatteluna. Haastateltavat edustivat USA:n ja Euroopan johtavia eläinruokavalmistajia ja pakkausten jatkojalostajia. Työn tuloksena saatiin yksityiskohtaista tietoa asiakkaiden odotuksista eläinruokapakkauksille, paperin ominaisuuksille ja paperitoimittajille. Lisäksi mallinnettiin ostoprosesseja paperitoimittajien, pakkausten jalostajien ja eläinruokavalmistajien välillä. Tulosten perusteella on analysoitu yrityksen mahdollisuuksia menestyä uudella markkinasegmentillä. Lisäksi työssä annettiin ehdotuksia tuotekehitys- ja markkinastrategian muodostamiseen.