Receiver operating characteristic (ROC) curve for classification of18F-NaF uptake on PET/CT

Abstract Objective: To assess the cutoff values established by ROC curves to classify18F-NaF uptake as normal or malignant. Materials and Methods: PET/CT images were acquired 1 hour after administration of 185 MBq of18F-NaF. Volumes of interest (VOIs) were drawn on three regions of the skeleton as follows: proximal right humerus diaphysis (HD), proximal right femoral diaphysis (FD) and first vertebral body (VB1), in a total of 254 patients, totalling 762 VOIs. The uptake in the VOIs was classified as normal or malignant on the basis of the radiopharmaceutical distribution pattern and of the CT images. A total of 675 volumes were classified as normal and 52 were classified as malignant. Thirty-five VOIs classified as indeterminate or nonmalignant lesions were excluded from analysis. The standardized uptake value (SUV) measured on the VOIs were plotted on an ROC curve for each one of the three regions. The area under the ROC (AUC) as well as the best cutoff SUVs to classify the VOIs were calculated. The best cutoff values were established as the ones with higher result of the sum of sensitivity and specificity. Results: The AUCs were 0.933, 0.889 and 0.975 for UD, FD and VB1, respectively. The best SUV cutoffs were 9.0 (sensitivity: 73%; specificity: 99%), 8.4 (sensitivity: 79%; specificity: 94%) and 21.0 (sensitivity: 93%; specificity: 95%) for UD, FD and VB1, respectively. Conclusion: The best cutoff value varies according to bone region of analysis and it is not possible to establish one value for the whole body.

IMP2 provides an alternative to LIN28B for LET-7 target gene protection and glioma stem cell maintenance

Glioblastoma multiforme (GBM) is the most frequent and lethal primary brain tumor in adults. Accumulating evidence suggests that tumors comprise a hierarchical organization that is, at least partially, not genetically driven. Cells that reside at the apex of this hierarchy are commonly referred to as cancer stem cells (CSCs) and are believed to largely contribute to recurrence and therapeutic failure. Although the complexity of epigenetic regulation of the genome precludes prediction as to which epigenetic changes dominate CSC specification in different cancer types, the ability of microRNAs (miRNAs) to fine-tune expression of entire gene networks places them among prime candidates for establishing CSC properties. In this study we characterized the miRNA expression profile of primary GBM grown either under conditions that enrich for GSCs or their differentiated non-tumorigenic progeny (DGCs). Although, we identified a subset of miRNAs that was strongly differentially expressed between GSCs and DGCs, we observed that in GSCs both let-7 and, paradoxically, their target genes are highly expressed, suggesting protection against let-7 action. Using PAR-CLIP we show that insulin-like growth factor-2 mRNA-binding protein 2 (IMP2) provides a mechanism for let-7 target gene protection that represents an alternative to LIN28A/B, which abrogates let-7 biogenesis in normal embryonic and certain malignant stem cells. By direct binding to miRNA recognition elements, IMP2 protects its targets from let-7 mediated decay. Importantly, depletion of IMP2 in GSCs strongly impairs their self- renewal properties and tumorigenicity in vivo, a phenotype that can be rescued by expression of LIN28B, suggesting that IMP2 mainly contributes to GSC maintenance by protecting let-7 target genes from silencing. Using mouse models, we show that depletion of IMP2 in neural stem cells (NSCs) induces let-7 target gene down-regulation, impairs their clonogenic capacity, and affects differentiation. Taken together, our observations describe a novel regulatory function of IMP2 in the let-7 axis whereby it supports GSC and NSC specification. Résumé (Français) Le glioblastome (GBM) est la tumeur primaire maligne du cerveau la plus fréquente. De nombreuses études ont démontré l'existence d'une organisation hiérarchique des cellules cancéreuses liée à des mécanismes épigénétiques. Les cellules qui se trouvent au sommet de cette hiérarchie sont appelées cellules souches cancéreuses (CSC), et contribuent à l'échec thérapeutique. Bien que la complexité des régulateurs épigénétiques permette difficilement de prédire quel mécanisme contribue le plus aux propriétés des CSC, la capacité des microRNAs (miRNAs) de réguler des réseaux entiers de gènes, les placent comme des candidats de premiers choix. Ici, nous avons caractérisé le profil d'expression des miRNAs dans des tumeurs primaires de GBM cultivées dans des conditions qui enrichissent soit pour les CSC, soit pour leur contrepartie de cellules cancéreuses différences (CCD). De manière surprenante et paradoxale la famille de miRNA let-7 et leurs gènes cibles étaient hautement exprimés dans les CSC, suggérant un mécanisme de protection contre l'action des let-7. Avec l'aide de la technologie PAR-CLIP, nous démontrons que la protéine IMP2, protège les mRNAs de l'action des let-7 et représente une alternative à Lin28A/B, qui d'ordinaire réprime fortement la maturation des let-7 dans les cellules souches embryonnaires et divers cancers. En se liant à la région ciblée par les let-7, IMP2 protège ses transcrits de l'action de cette classe de microRNA qui est tumoro-supressive. La déplétion d'IMP2 dans des CSC de GBM réduit fortement leur clonogénicité in vitro et leur tumorigénicité in vivo. Ceci peut être reversé en introduisant Lin28B dans des CSC de GBM, suggérant qu'IMP2 exerce ses fonctions pro-tumorigéniques en modulant l'axe let-7. Avec l'aide de modèles murins, nous observons que la déplétion de IMP2 dans les cellules souches neurales (CSN) induit une baisse de leur clonogénicité et des cibles des miRNAs let-7, suggérant une conservation de ce mécanisme entre les CSC de GBM et les CSN. En résumé, nos observations définissent une nouvelle fonction de IMP2 dans l'axe let-7 par lequel il contribue au maintien des propriétés des CSC et des CSN.

Russian Enterprise Restructuring - the Effect of Privatisation and Market Liberalisation on the Performance of Large Enterprises

The fundamental question in the transitional economies of the former Eastern Europe and Soviet Union has been whether privatisation and market liberalisation have had an effect on the performance of former state-owned enterprises. This study examines the effect of privatisation, capital market discipline, price liberalisation and international price exposure on the restructuring of large Russian enterprises. The performance indicators are sales, profitability, labour productivity and stock market valuations. The results do not show performance differences between state-owned and privatised enterprises. On the other hand, the expansion of the de novo private sector has been strong. New enterprises have significantly higher sales growth, profitability and labour productivity. However, the results indicate a diminishing effect of ownership. The international stock market listing has a significant positive effect on profitability, while the effect of domestic stock market listing is insignificant. The international price exposure has a significant positive increasing effect on profitability and labour productivity. International enterprises have higher profitability only when operating on price liberalised markets, however. The main results of the study are strong evidence on the positive effects of international linkages on the enterprise restructuring and the higher than expected role of new enterprises in the Russian economy.

Teknologiainvestointien vaikutus huonekaluja valmistavien yritysten kannattavuuteen

Tutkimuksen tavoitteena oli selvittää Etelä-Pohjanmaalla huonekaluja valmistavien yritysten kone- ja laiteinvestointien vaikutusta yritysten kannattavuuteen. Toisena tavoitteena oli selvittää, millaisia investointiprosessia tukevia asiantuntijapalveluja yritykset ovat käyttäneet teknologiainvestointien yhteydessä sekä millaisille palveluille yrityksillä on tarvetta. Kannattavuuden tarkastelu kohdistui viiden huonekalutehtaan tilinpäätöstietoihin. Tarkasteltavaan yritysryhmään valittiin yritykset, jotka ovat investoineet selkeästi EU:n keskimääräistä investointitasoa enemmän. Kannattavuusvertailun mittareiksi valittiin liikevaihdon määrä henkilöä kohden, käyttökate, liikevoitto ja sijoitetun pääoman tuotto. Palvelutarvekysely kohdistui myös viiteen yritykseen, jotka olivat osin samoja yrityksiä kuin kannattavuustarkastelussa. Haastattelun avulla kartoitettiin yritysten kone- ja laiteinvestointien suunnittelu- ja käyttöönottovaiheen asiantuntijapalveluiden käyttöä ja niistä saatuja kokemuksia sekä kysyttiin yritysten tarpeet uusille asiantuntijapalveluille. Kannattavuustutkimuksen tuloksena voidaan havaita, että keskimääräistä enemmän koneisiin ja laitteisiin investoineet huonekaluyritykset toimivat kannattavammin kuin ne yritykset, jotka eivät tee merkittäviä investointeja. Haastattelututkimuksen tuloksena voidaan todeta, että yritykset ovat käyttäneet pääasiassa oman tilitoimiston palveluja investointien kannattavuutta ja tuotantokapasiteettia arvioidessaan. Koneiden käyttöönotossa yritykset ovat käyttäneet lähinnä koneiden maahantuojien koulutus- ja asennuspalveluja. Uusina palvelutarpeina esiin nousi koneiden tekninen vertailu ja investointiavustusten ja -lainojen hakuprosessia tukevat palvelut.

Factors of customer project profitability in an engineering industrial enterprise

The purpose of the study is to find factors affecting projects' profitability in project business. The issue is approached from customer profitability and project management point of view. The study has been made for a big Finnish company acting in a global market place. The research method is quantitative. Research hypotheses are based on the literature. The used database is originated from the company's ERP- (enterprise resource planning) and project financial follow-up —system. The findings of the study supported the hypotheses weakly. Obviously profitability fluctuated depending on a customer and a project manager. The reasons could not be justified with the variables used in the research.

Mobile Subscription Acquisition and Retention Costs - An Actvity-Based Model

The objective of this master’s thesis was to develop a model for mobile subscription acquisition cost, SAC, and mobile subscription retention cost, SRC, by applying activity-based cost accounting principles. The thesis was conducted as a case study for a telecommunication company operating on the Finnish telecommunication market. In addition to activity-based cost accounting there were other theories studied and applied in order to establish a theory framework for this thesis. The concepts of acquisition and retention were explored in a broader context with the concepts of customer satisfaction, loyalty and profitability and eventually customer relationship management to understand the background and meaning of the theme of this thesis. The utilization of SAC and SRC information is discussed through the theories of decision making and activity-based management. Also, the present state and future needs of SAC and SRC information usage at the case company as well as the functions of the company were examined by interviewing some members of the company personnel. With the help of these theories and methods it was aimed at finding out both the theory-based and practical factors which affect the structure of the model. During the thesis study it was confirmed that the existing SAC and SRC model of the case company should be used as the basis in developing the activity-based model. As a result the indirect costs of the old model were transformed into activities and the direct costs were continued to be allocated directly to acquisition of new subscriptions and retention of old subscriptions. The refined model will enable managing the subscription acquisition, retention and the related costs better through the activity information. During the interviews it was found out that the SAC and SRC information is also used in performance measurement and operational and strategic planning. SAC and SRC are not fully absorbed costs and it was concluded that the model serves best as a source of indicative cost information. This thesis does not include calculating costs. Instead, the refined model together with both the theory-based and interview findings concerning the utilization of the information produced by the model will serve as a framework for the possible future development aiming at completing the model.

Ajopuusta asiantuntijaksi – luottamushenkilöarvioinnin merkitys kunnan johtamisessa ja päätöksenteossa

Tässä johtaminen ja organisaatiot –oppialaan kuuluvassa väitöstutkimuksessa selvitetään luottamushenkilöarvioinnin merkitystä kunnan johtamisessa ja päätöksenteossa. Tutkimuksessa kuvataan luottamushenkilöiden tekemää kunnan talouden ja hallinnon arviointia ja sen merkitystä kunnan johtamisen ja päätöksenteon palautemekanismina. Empiirisen haastatteluaineiston avulla kuvataan eteläkarjalaisten tarkastuslautakuntien toimintaa ja niiden puheenjohtajina toimineiden henkilöiden kokemuksia tarkastuslautakuntien olemassaolon kahdella ensimmäisellä valtuustokaudella 1997–2000 ja 2001–2004. Tutkimus kohdistuu julkiselle sektorille, kuntien poliittis-hallinnolliseen päätöksentekoon. Tarkastuslautakuntien synnyn taustalla ymmärretään vaikuttavan yleisenä viitekehyksenä erityisesti New Public Managementin (NPM) eli uuden julkisjohtamisen ilmaisemat ajatukset mm. toimintojen tehokkuudesta, tuloksellisuudesta ja vaikuttavuudesta sekä arvioinnista osana päätöksentekoa. Tutkimuksessa hyödynnetään kehysteoriana uuden julkisjohtamisen doktriinia ja substanssiteoriana arviointiin ja arviointitutkimukseen liittyvää teoreettista tietovarantoa. Tutkimuksen ensisijainen empiirinen aineisto koostuu 16 tarkastuslautakunnan puheenjohtajan haastattelusta, jotka on analysoitu sisällönanalyysiä käyttäen. Tausta-aineistona on käytetty 112 tarkastuslautakuntien arviointikertomusta. Tutkimus on ensimmäinen väitöskirjatasoinen työ tältä aihealueelta. Työn keskeinen kontribuutio on tutkimuksessa esitettävä näkemys luottamushenkilöarvioinnista ja sen merkityksestä kunnan johtamisessa arviointitutkimuksen, uuden julkisjohtamisen ja tarkastuslautakunnista tähän mennessä tehtyjen tutkimusten sekä empiirisen haastattelututkimuksen pohjalta. Luottamushenkilöarvioinnin painopisteen nähdään siirtyneen tarkastuslautakunnan lainmukaisen tehtävänannon eli valtuuston asettamien taloudellisten ja toiminnallisten tavoitteiden toteutumisen arvioinnista kunnan toiminnan kehittämiseen, jolloin sillä on konkreettisemmin päätöksentekoa tukeva merkitys. Taaksepäin suuntautunutta arviointia ei koeta kovinkaan merkitykselliseksi, vaikka virheistä oppimisen näkökulmasta ja päätöksenteon palautemekanismina myös ex post –arviointi on tärkeää. Tutkimuksessa on sovellettu poikkitieteellistä lähestymistapaa organisaatiotutkimuksen ja uuden julkisjohtamisen, arviointitutkimuksen sekä kuntatutkimuksen näkökulmia yhteen sovittamalla. Tutkimuksessa esitetään väite, että tarkastuslautakuntia kahlitsee niiden voimakas yhteys ja perustuminen tilintarkastukseen. Tarkastuslautakuntien arviointi ei ole kehittynyt omaehtoisesti ja luottamushenkilöarvioinnin merkitys on vielä osin tunnistamatta eritoten johtamisen itsensä arvioinnin näkökulmasta.

Analyzing customer profitability: an empirical study

The purpose of this study was to define the customer profitability of the case company as well as to specify the factors that explain customer profitability. The study was made with a quantitative research method. The research hypotheses were formulated mainly on the grounds of previous research, and were tested with statistical research methods. The research results showed that customer profitability is not equally distributed among the customers of the case company, and the majority of its customers is profitable. The interpreters for absolute customer profitability were sales volume and the customer’s location region. The interpreters for relative customer profitability were the customer’s location region and the product segment into which a customer can be classified on the basis of the products that were sold to this customer.

Creating a customer profitability accounting model

Customer profitability accounting is a well-researched topic in the academic field, and it has been proved to posses rather undisputable benefits. However, the calculation of the customer profitabilities can be challenging, therefore the usage of the accounting is not self-explanatory in organizations. The aim of this study was to create a customer profitability accounting model for a wholesales unit in the case company to function as a sales management tool. The literature review of the study presents certain fundamental issues related to customer profitability accounting, in addition a theoretical framework for accounting model design is provided. The creation of the model was commenced by setting the requirements for it and examining the foundation of the model design, which consisted of for instance price setting and cost structure of products. This was followed by selecting approaches to the creation of the model. The result of the study was an accounting model, for which a determination of included revenues and costs was executed, along with the formulation of an allocation criteria of the costs. Lastly, the customer profitabilities were calculated in accordance with the accounting principles and the calculation logic of the model. The attained figures proved the model to provide an appropriate solution for obtaining the customer profitabilities and thus to use the accounting information as a sales management tool in for instance decision making and negotiation situations.

Yritysjärjestelyiden vaikutus lyhyen aikavälin osaketuottoihin ja pitkän aikavälin kannattavuuteen Suomen markkinoilla

Tutkimuksen tavoitteena on selvittää yritysjärjestelyiden vaikutuksia Suomen markkinoilla, sekä tutkia onko yritysjärjestelyiden eroavaisuuksilla vaikutusta menestymiseen. Yritysjärjestelyt ryhmitellään maksutavan, koon, kansainvälisyyden ja markkina-arvo/kirja-arvon perusteella. Tutkimuksen aineisto koostuu 31 yritysjärjestelystä, joissa ainakin toinen osapuoli on ilmoitushetkellä ollut listattuna Helsingin pörssiin. Tutkimukseen valitut yritysjärjestelyt ovat tapahtuneet vuosien 1999-2007 välillä. Tutkimus suoritetaan kahdella eri menetelmällä: markkinaperusteisia tuottoja ja yritysten taloudellista informaatiota analysoimalla. Markkinaperusteisia tuottoja tutkitaan epänormaaleiden tuottojen avulla. Taloudelliseen informaatioon perustuvaa kannattavuutta tutkitaan kassavirran ja operatiivisen tuloksen avulla, jotka suhteutetaan yritysten markkina-arvoon ja liikevaihtoon. Empiiristen tulosten mukaan yritysjärjestelyt tuottavat ostettavan yrityksen osakkeenomistajille epänormaaleita tuottoja ja ostavan yrityksen osakkeenomistajille nollatuottoja. Tulokset ovat samankaltaisia kuin kansainvälisellä aineistolla aiemmin saadut. Taloudelliseen informaatioon perustuvat tulokset ovat ristiriitaisia mutta niistä on havaittavissa heikohko menestyminen yhdistymisen jälkeen.

Treatment of oily wastewater by ultrafiltration: The effect of different operating and solution conditions

In many industries, such as petroleum production, and the petrochemical, metal, food and cosmetics industries, wastewaters containing an emulsion of oil in water are often produced. The emulsions consist of water (up to 90%), oils (mineral, animal, vegetable and synthetic), surfactants and other contaminates. In view of its toxic nature and its deleterious effects on the surrounding environment (soil, water) such wastewater needs to be treated before release into natural water ways. Membrane-based processes have successfully been applied in industrial applications and are considered as possible candidates for the treatment of oily wastewaters. Easy operation, lower cost, and in some cases, the ability to reduce contaminants below existing pollution limits are the main advantages of these systems. The main drawback of membranes is flux decline due tofouling and concentration polarisation. The complexity of oil-containing systems demands complementary studies on issues related to the mitigation of fouling and concentration polarisation in membranebased ultrafiltration. In this thesis the effect of different operating conditions (factors) on ultrafiltration of oily water is studied. Important factors are normally correlated and, therefore, their effect should be studied simultaneously. This work uses a novel approach to study different operating conditions, like pressure, flow velocity, and temperature, and solution properties, like oil concentration (cutting oil, diesel, kerosene), pH, and salt concentration (CaCl2 and NaCl)) in the ultrafiltration of oily water, simultaneously and in a systematic way using an experimental design approach. A hypothesis is developed to describe the interaction between the oil drops, salt and the membrane surface. The optimum conditions for ultrafiltration and the contribution of each factor in the ultrafiltration of oily water are evaluated. It is found that the effect on permeate flux of the various factors studied strongly depended on the type of oil, the type of membrane and the amount of salts. The thesis demonstrates that a system containing oil is very complex, and that fouling and flux decline can be observed even at very low pressures. This means that only the weak form of the critical flux exists for such systems. The cleaning of the fouled membranes and the influence of different parameters (flow velocity, temperature, time, pressure, and chemical concentration (SDS, NaOH)) were evaluated in this study. It was observed that fouling, and consequently cleaning, behaved differently for the studied membranes. Of the membranes studied, the membrane with the lowest propensity for fouling and the most easily cleaned was the regenerated cellulose membrane (C100H). In order to get more information about the interaction between the membrane and the components of the emulsion, a streaming potential study was performed on the membrane. The experiments were carried out at different pH and oil concentration. It was seen that oily water changed the surface charge of the membrane significantly. The surface charge and the streaming potential during different stages of filtration were measured and analysed being a new method for fouling of oil in this thesis. The surface charge varied in different stages of filtration. It was found that the surface charge of a cleaned membrane was not the same as initially; however, the permeability was equal to that of a virgin membrane. The effect of filtration mode was studied by performing the filtration in both cross-flow and deadend mode. The effect of salt on performance was considered in both studies. It was found that salt decreased the permeate flux even at low concentration. To test the effect of hydrophilicity change, the commercial membranes used in this thesis were modified by grafting (PNIPAAm) on their surfaces. A new technique (corona treatment) was used for this modification. The effect of modification on permeate flux and retention was evaluated. The modified membranes changed their pore size around 33oC resulting in different retention and permeability. The obtained results in this thesis can be applied to optimise the operation of a membrane plant under normal or shock conditions or to modify the process such that it becomes more efficient or effective.

Painotuotteen hinnoittelu kypsillä markkinoilla

Tämä tutkimus tarkastelee hinnoittelua graafisen teollisuuden pk-sektorin kirjapainoissa. Alalla vallitseva markkinatilanne on kiristynyt siirryttäessä kysyntä-/teknologiaelinkaaren kasvujaksolta kypsään vaiheeseen. Tutkimus pyrkii antamaan vastauksen hinnoittelun tarvitsemaan toimintaan tarkastelemalla hinnoittelun ”ongelmien järjestelmää”. Tutkimus on toiminta-analyyttisen metodologian mukaisena tutkimuksena toteutettu case-tutkimus, jossa empirian tutkimusmetodeina ovat kvalitatiiviset puolistruktuuriset teemahaastattelut ja kvantitatiiviset tilastolliset tarkastelut toimialan kehityksestä. Tutkimustuloksina todetaan alalla vallinneen pitkän voimakkaan kannattavuuden jakson muokanneen case-yrityksen hinnoitteluperiaatteita, jotka vastaavat huonosti muuttuneeseen markkinatilanteeseen. Tutkimuksessa esitetään pk-yrittäjien rationaalisuuden ero talousteorioiden edellyttämästä instrumentaalisesta rationaalisuudesta.

Project and customer profitability analysis: an empirical case study

The objective of this case study is to provide a Finnish solution provider company an objective, in-depth analysis of their project based business and especially of project estimation accuracy. A project and customer profitability analysis is conducted as a complementary addition to describe profitability of the Case Company’s core division. The theoretical framework is constructed on project profitability and customer profitability analysis. Project profitability is approached starting from managing projects, continuing to project pricing process and concluding to project success. The empirical part of this study describes the Case Company’s project portfolio, and by means of quantitative analysis, the study describes how the characteristics of a project impact the project’s profitability. The findings indicate that it really makes a difference in project portfolio’s estimated and actual profitability when methods of installation and technical specifications are scrutinized. Implications on profitability are gathered into a risk assessment tool proposal.