Irinotecan and oxaliplatin: an overview of the novel chemotherapeutic options for the treatment of advanced colorectal cancer

Colorectal cancer is one of the most frequent malignancies in humans and an important cause of cancer death. Metastatic colorectal cancer remains incurable with available systemic therapeutic options. The most active cytotoxic drug against this malignancy, the antimetabolite 5-fluorouracil, was developed more than forty years ago, and as a single agent produces responses in only 10 to 15% of patients which in general last less than one year. Efforts to ameliorate these poor results resulted in the 5-fluorouracil/leucovorin combination, which enhances response rates about two-fold, without, however, significantly improving survival rates. The recent emergence of a handful of new 5-fluorouracil analogues and folate antagonists, as well as the topoisomerase I inhibitor irinotecan, and the third-generation platinum compound oxaliplatin, is likely to alter this gloomy scenario. These agents are at least as effective as 5-fluorouracil in patients with advanced colorectal carcinoma, both untreated and previously treated with 5-fluorouracil-based regimens. This has led to the approval of irinotecan as second-line treatment for 5-fluorouracil-refractory disease, while the use of oxaliplatin has been suggested for patients having a defective 5-fluorouracil catabolism. Recently, FDA approved the combination of irinotecan with 5-fluorouracil and leucovorin for first-line treatment of advanced colon cancer. Based on the synergistic preclinical antitumor effects of some of these agents, their meaningful single-agent activity, distinct mechanisms of cytotoxicity and resistance, and only partially overlapping toxicity profiles, effective combination regimens are now being developed, which are likely to lead to a new, more hopeful era for patients suffering from advanced colorectal carcinoma.

Comparison of Pavlovian serial conditional discrimination in rats and hamsters in the same experimental situation

The present study compares behavioral changes between two distinct rodent groups, hamsters (Mesocricetus auratus) and Wistar rats, when submitted in the same homogeneous experimental situations to a serial conditional discrimination procedure which involves water deprivation and the processing of temporal variables. Both hamsters and rats acquired serial positive conditional discrimination as indicated by higher frequencies of magazine-oriented behavior during the tone followed by reinforcement (T+) and preceded by the feature stimulus light (L) and during the empty interval, than during the tone alone not followed by reinforcement (T-). Rats' frequencies of magazine-oriented behavior were high during T+ and T-, initially during training, and decreased during T- as the training progressed. However, the hamsters' frequencies of magazine-oriented behavior started very low and increased only during T+ as the training progressed. Comparison of the frequencies of magazine-oriented behavior during the empty interval in relation to the frequencies during the preceding L period showed that rats' frequencies remained very high and hamsters' frequencies increased during training. These results suggest that rats and hamsters have different behavioral strategies for the acquisition of a conditional discrimination. The results of the comparisons made in these experiments support the view of the importance of an ecological psychology approach to the understanding of complex learning in animals.

Influence of the test situation on pup retrieval behavior of normal and undernourished lactating rats

Undernutrition of dams and pups disrupts the retrieval efficiency of mothers. However, if the mothers are assessed in their home cages, they spend more time with their litters. In the present study the effect of test conditions on pup retrieval behavior of mothers receiving a 25% (well-nourished group) and 8% casein diet (undernourished group) was examined. In agreement with previous studies, undernourished mothers spent more time with their litters than well-nourished dams as lactation proceeded. Pup retrieval behavior varied with test conditions. In the first experiment, the maternal behavior of dams was assessed by the standard procedure (pups were separated from their mother and scattered over the floor of the home cage). The mother was then returned and the number of retrieved pups was recorded. From day 3 to 8, the retrieval efficiency of undernourished dams decreased, while the retrieval efficiency of well-nourished mothers did not vary. In the second experiment, mothers were subjected to a single retrieval test (on day 9 of lactation) using the procedure described for experiment 1. No difference between well-nourished and undernourished mothers was observed. In the third experiment, seven-day-old pups were separated from the mothers and returned individually to a clean home cage. Dietary treatment did not affect the retrieval efficiency. However, undernourished dams reconstructed the nest more slowly than did well-nourished dams. Taken together, these results suggest that pup retrieval behavior of the undernourished mother is not impaired by dietary restriction when the maternal environment is disturbed minimally.

Children at psychiatric risk and their families in Bucharest, in the context of 25 years of changes after December 89’ Romanian Revolution

The aim of the present dissertation was to capture a picture of child and adolescent mental health in Romania, in the context of almost 25 years of changes following the Romanian Revolution of December ’89. A three-part study was carried out in order to provide consistent answers to the pre-defined objectives: to appraise the development of child and adolescent mental health services in Romania (Part I), to explore the characteristics of clinically-referred patients in a Romanian child and adolescent psychiatry department (Part II), to examine the children’s mental health state and its connections with family functioning and associated risk factors (Part III). A multi-method research approach was used, comprising one qualitative analysis and two quantitative research studies. Part I consisted of a comparative qualitative analysis of the answers given by 10 mental health professionals at a 12-questions open ended interview about the current situation in child and adolescent mental health in Romania, on three topics: changes, challenges, solutions. Part II involved a descriptive quantitative analysis of certain variables (e.g. age, gender, primary diagnosis, co-morbidities, time of hospitalization) conducted on the patients who had been admitted to the Child and Adolescent Psychiatry Department at “Prof. Dr. Alexandru Obregia” Psychiatry Hospital, Bucharest in 1991 and in 2013. Part III was conducted on 342 subjects enrolled in two clinical groups and one school group, this study being performed through a cross-sectional analysis on multi-informant child and adolescent mental health problems and competencies (CBCL, YSR, SDQ P, SDQ SR) and their interrelation with household information (HQ) and family functioning (FAD). Outlining the results it can be stated that: 1) The CAMH System in Romania is definitely set on the path of reorganization, including a higher involvement of beneficiaries and of the community. 2) The characteristics of the admitted patients have changed significantly during the last almost 25 years since `89 December Revolution, under the influence of word wide trends in child psychiatry and of administrative aspects of the mental health network in Romania. 3) The rates of main diagnoses and co-morbidities confirm the reports in literature, with Autism Spectrum Disorder being the most frequent childhood psychiatric disorders in this study. 4) The children’s mental health problems in the psychiatry group are comparable to those reported for other clinical populations. 5) Significant score differences were observed according to various household features and also meaningful associations between a child’s clinical status and different aspects of family functioning. The Romanian Child and Adolescent Psychiatry has started to adopt the norms and standards of the European Union. In the 25 years that have elapsed after the 1989 Revolution, many changes have occurred in Romanian CAMH, but many unresolved issues have also risen. Therefore, the major contribution of this thesis is that it provides a coherent and updated overview of the present-day situation from three different perspectives- those of mental healthcare professionals, the one observed in clinical patients and the one reported by children’s families.

A conceptual and practical overview of cDNA microarray technology: implications for basic and clinical sciences

cDNA microarray is an innovative technology that facilitates the analysis of the expression of thousands of genes simultaneously. The utilization of this methodology, which is rapidly evolving, requires a combination of expertise from the biological, mathematical and statistical sciences. In this review, we attempt to provide an overview of the principles of cDNA microarray technology, the practical concerns of the analytical processing of the data obtained, the correlation of this methodology with other data analysis methods such as immunohistochemistry in tissue microarrays, and the cDNA microarray application in distinct areas of the basic and clinical sciences.

Identification of characteristics for successful university-company partnership development

The importance of university-company collaboration has increased during the last decades. The drivers for that are, on the one hand, changes in business logic of companies and on the other hand the decreased state funding of universities. Many companies emphasize joint research with universities as an enabling input to their development processes, which aim at creating new innovations, products and wealth. These factors have changed universities’ operations and they have adopted several practices of dynamic business organizations, such as strategic planning, monitoring and controlling methods of internal processes etc. The objective of this thesis is to combine different characteristics of successful university-company partnership and its development. The development process starts with identifying potential partners in the university’s interest group, which requires understanding the role of different partners in the innovation system. Next, in order to find a common development basis, matching the policy and strategy between partners is needed. The third phase is to combine the academic and industrial objectives of a joint project, which is a typical form of university-company collaboration. The optimum is a win-win situation where both partners, universities and companies, can get addedvalue. For the companies added value typically means access to new research results before their competitors. For the universities added value offers a possibility to carry on high level scientific work. The research output in the form of published scientific articles is evaluated by the international science community. Because the university-company partnership is often executed by joint projects, the different forms of this kind of projects is discussed in this study. The most challenging form of collaboration is a semi-open project model, which is not based on bilateral activities between universities and companies but on a consortium of several universities, research institutes and companies. The universities and companies are core actors in the innovation system. Thus the discussion of their roles and relations to public operators like publicly funded financiers is important. In the Finnish innovation system there are at least the following doers executing strategies and policies: EU, Academy of Finland and TEKES. In addition to these, Strategic Centres for Science, Technology and Innovation which are owned jointly by companies, universities and research organizations have a very important role in their fields of business. They transfer research results into commercial actions to generate wealth. The thesis comprises two parts. The first part consists of an overview of the study including introduction, literature review, research design, synthesis of findings and conclusions. The second part introduces four original research publications.

Examining life-course influences on chronic disease: the importance of birth cohort studies from low- and middle- income countries. An overview

The objectives of this overview are to describe the past and potential contributions of birth cohorts to understanding chronic disease aetiology; advance a justification for the maintenance of birth cohorts from low- and middle-income countries (LMIC); provide an audit of birth cohorts from LMIC; and, finally, offer possible future directions for this sphere of research. While the contribution of birth cohorts from affluent societies to understanding disease aetiology has been considerable, we describe several reasons to anticipate why the results from such studies might not be directly applied to LMIC. More than any other developing country, Brazil has a tradition of establishing, maintaining and exploiting birth cohort studies. The clear need for a broader geographical representation may be precipitated by a greater collaboration worldwide in the sharing of ideas, fieldwork experience, and cross-country cohort data comparisons in order to carry out the best science in the most efficient manner. This requires the involvement of a central overseeing body - such as the World Health Organization - that has the respect of all countries and the capacity to develop strategic plans for `global' life-course epidemiology while addressing such issues as data-sharing. For rapid progress to be made, however, there must be minimal bureaucratic entanglements.

Palveluprosessin kehittäminen kampaamoketjussa

As the competitive situation becomes more intense, companies must strive for growth and the ability to renew themselves. Innovations and the development of services will take an important role in this situation. Involving users in the service design process creates additional value and a chance to stand out from the com-petition. The goal of the target company is to produce high-quality services with the customers' needs in mind. This is why the company wants to develop their services systematically and aims to collect information about the service needs of both their employees and customers, which can be used to develop new and ap-pealing service packages. The aim of the study is to find out what the target company's current service pro-cess is like and how it can be developed further. The work is a case study in which the development process of the new service is followed through according to the approach, process and tools of the service design. Information is collected through focused interviews and a client survey. Participant observation gave a good overview of how employees of the target company react to the development of services. The study also found that the ser-vice path enables the collecting of ideas concerning the practical planning and development of the service process.

Construction de l'Est et de l'Ouest : vers des compétences interculturelles. Un exemple de recherche à Hong-Kong en situation de mobilité académique

Numerous scholars have already stressed the need to prepare students prior to academic mobility (Abdallah-Pretceille, 2003; Jackson, 2013, for example) in order to face hypermodernity (Aubert, 2004). As per the new mobilities paradigm (Urry, 2007), this implies considering individuals at the centre of political and institutional issues. Furthermore, the multiplicity of terminology of references towards academic mobility, and intercultural competences, justifies this research. The theory, for this doctoral dissertation, applies “renewed interculturality” (Dervin, 2012), a move away from a culturalist approach. Intercultural competences are therefore defined as a stepping back from discourses on the Other that may emerge during encounters. In order to collect the data, six focus groups have been organised with two batches of students from a Higher Education Institution in Hong-Kong, an “education hub” (Dervin & Machart, 2014) that is striving to be competitive particularly in increasing the number of incomingand outcoming students. Training and education to interculturality have been implemented prior to academic mobility in order to observe the impact on participants’ discourses before and after the mobility. Theories of enunciation and dialogism represent the methodology allowing us to compare and analyse the reported voices in the participants’ discourse and their prosodic realisation (Martin & White, 2005) before and after the experience of academic mobility. I have attempted to observe the dialogic space available to welcome the Other during encounters in the participants’ discourse. The results seem to underline the increased number of reported voices in participants’ discourse after study abroad, but as the space opened for negotiation is instable and depends on the interlocutors and the voices addressed, consequently, further research appears necessary to study the influences of a preparation prior to mobility on the contraction or expansion of heteroglossia. All in all, this doctoral dissertation aimed to renew preparation

Individual Crimes or a Sociological Phenomenon: A Critical discourse analysis of the 2014 Royal Canadian Mounted Police National Operational Overview on missing and murdered Indigenous women in Canada

Pro gradu -tutkielma käsittelee Kanadan poliisivoimien, Royal Canadian Mounted Police (RCMP), vuoden 2014 operationaalista raporttia Kanadan kadonneista ja murhatuista alkuperäiskansojen naisista. Heitä katoaa ja murhataan Kanadassa suhteessa huomattavasti enemmän kuin muita naisia. Aihe on hyvin ajankohtainen sekä kriittinen ja siihen on paikallisten organisaatioiden lisäksi kiinnittänyt huomiota mm. Amnesty International ja Yhdistyneet Kansakunnat. Tilannetta pidetään jo ihmisoikeuskriisinä ja sen puolesta puhuminen voidaan nähdä osana laajempaa kansannousua alkuperäiskansojen oikeuksien puolesta. Kanadan hallitusta sekä poliisivoimia on syytetty välinpitämättömyydestä ja rasismista, poliiseja jopa väkivallasta alkuperäiskansojen naisia kohtaan. Kanadan hallitus ei myönnä ongelman olevan sosiologinen ilmiö, vaan pääministerin mukaan naisten katoamiset ja murhat ovat yksittäisiä rikoksia. Tilanteen taustalla on laajempi ongelma, joka juontaa juurensa kolonialismista, alkuperäiskansojen pakkokoulutuksesta ja heidän kulttuurinsa sekä identiteettinsä tuhoamisesta. Ennakkoluulot ja stereotypiat elävät yhä vahvana luoden heikon aseman alkuperäiskansojen edustajille ja tässä tapauksessa erityisesti naisille, joita myös usein syytetään omista ongelmistaan. Tutkielma selvittää, onko tämä operationaalinen raportti eriarvoisuutta, stereotypioita sekä ennakkoluuloja ylläpitävä ja tukeeko se näkemystä sosiologisesta ilmiöstä. Poliisivoimat ovat yhteiskunnassa vaikutusvaltaisessa asemassa ja voivat edesauttaa, jatkaa ja voimistaa syrjivää ajattelua, käytöstä ja viestintää. Vaikka he myös ajavat alkuperäiskansojen etuja, tulee heidän toimintaansa ja täten tätä kyseistä raporttia tarkastella kriittisesti. Tutkielma keskittyy kriittiseen diskurssianalyysiin (Fairclough 1995, Wodak & Meyer 2009). Raportin teksti ei ole avoimesti diskriminoivaa ja keskittyy tilastojen ja lukujen raportointiin sekä vertailuun, luoden samalla kuvan asianomaisista sekä tilanteesta yleisesti. Makroanalyysi (van Dijk 1977, 1980) mahdollistaa korkeamman tason ajatusten ja ideoiden esille tuonnin paljastaen ns. rivien välistä löytyvän viestinnän. Näistä makroanalyysin tuloksista etsitään erilaisia diskurssistrategioita (Reisigl & Wodak 2001), joiden avulla luodaan mm. kuva positiivisesta itsestä ja negatiivisesta toisesta. Näitä tuloksia tuetaan lyhyellä multimodaalisella analyysillä, joka keskittyy lähinnä raportin kahteen kuvaan (Kress & van Leeuwen 2006). Lopuksi tuloksista keskustellaan suhteessa yhteiskunnan valtasuhteisiin (Foucault 1976), rasismiin ja seksismiin. Analyysin perusteella raportti on selkeästi diskriminoiva. Se tuo esiin vanhoja stereotypioita ja ennakkoluuloja, esittää tilanteen alkuperäiskansojen sisäisenä ongelmana, jättää mainitsematta tilanteen taustat ja luo hyvin positiivisen kuvan poliisivoimista (RCMP). Tällä tavoin se ylläpitää yhteiskunnan epätasapainoisia valtasuhteita ja alkuperäiskansojen naisten heikompaa ja marginalisoitua asemaa. Raportti todistaa kuinka syvällä Kanadan yhteiskunnassa jopa institutionaalisella tasolla nämä ajatukset piilevät, sillä diskriminaatio ulottuu tapausten syistä niiden käsittelyyn ja raportointiin. Tilanne on huolestuttava ja voidaan nähdä sosiologisena ilmiönä. Poliisivoimien tulisi lisätä sisäistä koulutusta asian suhteen sekä hallituksen tutkia tätä ilmiönä ja paneutua sen selvittämiseen laaja-alaisesti ja läpinäkyvästi.

Individual Crimes or a Sociological Phenomenon: A Critical discourse analysis of the 2014 Royal Canadian Mounted Police National Operational Overview on missing and murdered Indigenous women in Canada

Pro gradu -tutkielma käsittelee Kanadan poliisivoimien, Royal Canadian Mounted Police (RCMP), vuoden 2014 operationaalista raporttia Kanadan kadonneista ja murhatuista alkuperäiskansojen naisista. Heitä katoaa ja murhataan Kanadassa suhteessa huomattavasti enemmän kuin muita naisia. Aihe on hyvin ajankohtainen sekä kriittinen ja siihen on paikallisten organisaatioiden lisäksi kiinnittänyt huomiota mm. Amnesty International ja Yhdistyneet Kansakunnat. Tilannetta pidetään jo ihmisoikeuskriisinä ja sen puolesta puhuminen voidaan nähdä osana laajempaa kansannousua alkuperäiskansojen oikeuksien puolesta. Kanadan hallitusta sekä poliisivoimia on syytetty välinpitämättömyydestä ja rasismista, poliiseja jopa väkivallasta alkuperäiskansojen naisia kohtaan. Kanadan hallitus ei myönnä ongelman olevan sosiologinen ilmiö, vaan pääministerin mukaan naisten katoamiset ja murhat ovat yksittäisiä rikoksia. Tilanteen taustalla on laajempi ongelma, joka juontaa juurensa kolonialismista, alkuperäiskansojen pakkokoulutuksesta ja heidän kulttuurinsa sekä identiteettinsä tuhoamisesta. Ennakkoluulot ja stereotypiat elävät yhä vahvana luoden heikon aseman alkuperäiskansojen edustajille ja tässä tapauksessa erityisesti naisille, joita myös usein syytetään omista ongelmistaan. Tutkielma selvittää, onko tämä operationaalinen raportti eriarvoisuutta, stereotypioita sekä ennakkoluuloja ylläpitävä ja tukeeko se näkemystä sosiologisesta ilmiöstä. Poliisivoimat ovat yhteiskunnassa vaikutusvaltaisessa asemassa ja voivat edesauttaa, jatkaa ja voimistaa syrjivää ajattelua, käytöstä ja viestintää. Vaikka he myös ajavat alkuperäiskansojen etuja, tulee heidän toimintaansa ja täten tätä kyseistä raporttia tarkastella kriittisesti. Tutkielma keskittyy kriittiseen diskurssianalyysiin (Fairclough 1995, Wodak & Meyer 2009). Raportin teksti ei ole avoimesti diskriminoivaa ja keskittyy tilastojen ja lukujen raportointiin sekä vertailuun, luoden samalla kuvan asianomaisista sekä tilanteesta yleisesti. Makroanalyysi (van Dijk 1977, 1980) mahdollistaa korkeamman tason ajatusten ja ideoiden esille tuonnin paljastaen ns. rivien välistä löytyvän viestinnän. Näistä makroanalyysin tuloksista etsitään erilaisia diskurssistrategioita (Reisigl & Wodak 2001), joiden avulla luodaan mm. kuva positiivisesta itsestä ja negatiivisesta toisesta. Näitä tuloksia tuetaan lyhyellä multimodaalisella analyysillä, joka keskittyy lähinnä raportin kahteen kuvaan (Kress & van Leeuwen 2006). Lopuksi tuloksista keskustellaan suhteessa yhteiskunnan valtasuhteisiin (Foucault 1976), rasismiin ja seksismiin. Analyysin perusteella raportti on selkeästi diskriminoiva. Se tuo esiin vanhoja stereotypioita ja ennakkoluuloja, esittää tilanteen alkuperäiskansojen sisäisenä ongelmana, jättää mainitsematta tilanteen taustat ja luo hyvin positiivisen kuvan poliisivoimista (RCMP). Tällä tavoin se ylläpitää yhteiskunnan epätasapainoisia valtasuhteita ja alkuperäiskansojen naisten heikompaa ja marginalisoitua asemaa. Raportti todistaa kuinka syvällä Kanadan yhteiskunnassa jopa institutionaalisella tasolla nämä ajatukset piilevät, sillä diskriminaatio ulottuu tapausten syistä niiden käsittelyyn ja raportointiin. Tilanne on huolestuttava ja voidaan nähdä sosiologisena ilmiönä. Poliisivoimien tulisi lisätä sisäistä koulutusta asian suhteen sekä hallituksen tutkia tätä ilmiönä ja paneutua sen selvittämiseen laaja-alaisesti ja läpinäkyvästi.

Hare's preference utilitarianism: an overview and critique

My purpose in this paper is to summarize some aspects of utilitarianism and to provide a general overview of Hare's preference utilitarianism, followed by a critique of Hare's preference theory.

Modularity in Health and Social Services: Perspectives on Organization and Management

Organizations that provide health and social services operate in a complex and constantly changing environment. Changes occur, for example, in ageing, technology and biotechnology, and customers’ expectations, as well as the global economic situation. Organizations typically aim to adapt the changes by introducing new organizational structures and managerial practices, such as process and lean management. Only recently has there been an interest in evaluating whether organizations providing health and social services could apply modularity in order to respond to some of the changes. The concept of modularity originates from manufacturing, but is applied in many other disciplines, such as information technology and logistics. However, thus far, the literature concerning modularity in health and social services is scarce. Therefore the purpose of this thesis is to increase understanding concerning modularity and the possibilities to apply modularity in the health and social services context. In addition, the purpose is to shed light on the viewpoints that are worth taking into account when considering the application of modularity in the health and social services context. The aim of the thesis is to analyze the way in which the modular structures are applied in the health and social services context and to analyze what advantages and possible barriers, as well as managerial concerns, might occur if modularity is applied in the health and social services context. The thesis is conducted by using multiple methods in order to provide a broad aspect to the topic. A systematic literature review provided solid ground for pre-understanding the topic and supported the formulation of the research questions. Theoretical reasoning provided a general overview of the special characteristics of the health and social services context and their effect on application of modularity. Empirical studies concentrated on managerial concerns of modularity particularly from the perspective of health and social services for the elderly. Results of the thesis reveal that structures in products, services, processes, and organizations are rather modular in health and social services. They can be decomposed in small independent units, while the challenges seem to occur especially in the compatibility of the services. It seems that health and social services managers have recognized this problem and they are increasingly paying attention to this challenge in order to enhance the flexible compatibility of services. Advantages and possible barriers of modularity are explored in this thesis, and from the theoretical perspective it could be argued that modularity seems to be beneficial in the context of health and social services. In fact, it has the potential to alleviate several of the challenges that the health and social services context is confronting. For example, modular structures could support organizations in their challenging task to respond to customers’ increasing demand for heterogeneous services. However, special characteristics of the health and social services context create barriers and provide significant challenges in application of modularity. For example, asymmetry of information, negative externalities, uncertainty of demand, and rigid regulation prevent managers from extensively drawing benefits from modularity. Results also reveal that modularity has managerial implications in health and social service. Modularity has the potential to promote and support new service development and outsourcing. Results also provide insights into network management and increases managerial understanding of different network management strategies. Standardization in health and social services is extensive due to legislation and recommendations. Modularity provides alternative paths to take an advantage of standardization while still ensuring the quality of the services. Based on this thesis, it can be concluded, both from a theoretical perspective and from empirical results concerning modularity in health and social services, that modularity might fit well and be beneficial. However, the special characteristics of the health and social services context prevent some of the benefits of modularity and complicate its application. This thesis contributes to the academic literature on the organization and management of health and social services by describing modularity as an alternative way for organizing and managing health and social services. In addition, it contributes to the literature of modularity by exploring the applicability of modularity in the context of health and social services. It also provides practical contribution to health and social services managers by evaluating the pros and cons of modularity when applied to health and social services.