Oncolytic Adenoviruses with Radiation Therapy for Treatment of Prostate Cancer

Prostate cancer is the most common cancer in males. Although many patients with localized disease can be cured with surgery and radiotherapy, advanced disease and especially castration resistant metastatic disease remains incurable, with a median life expectancy of less than 18 months. Oncolytic adenoviruses (Ads) are a new promising treatment against cancer due to their innate capacity to kill cancer cells. Viral replication in tumor cells leads to oncolysis and production of a multiplicity of new virions that are capable of further destroying cancerous tissue. Oncolytic Ads can be modified for tumor targeted infection and replication and be armed with therapeutic transgenes to maximize the oncolytic effect. Worldwide, clinical trials with oncolytic Ads have demonstrated good safety while the antitumor efficacy remains to be improved. Importantly, the best responses have been reported when oncolytic adenoviruses have been combined with standard cancer treatments, such as chemotherapy and radiation. Further, a challenge in many virotherapy approaches has been the monitoring of virus replication in vivo. Reporter genes have been extensively used as transgenes to evaluate the biodistribution of the virus and activity of specific promoters. However, these techniques are often limited to preclinical evaluation and not amenable to human use. The aim of the thesis was to find and develop new oncolytic Ads with maximum efficacy against metastatic, castration resistant prostate cancer and study them in vitro and in vivo combined to different forms of radiation therapy. Using combination therapy, we were aiming for better antitumor efficacy with reduced side effects. Capsid modified Ads for enhanced transduction were studied. Serotype 3 targeted chimera, Ad5/3, was found to have enhanced infectivity for prostate cancer and was used for developing new viruses for the study. Correlation between Ad-encoded marker peptide secretion and simultaneous viral replication was evaluated and the effects of radiotherapy on viral replication were studied in detail. We found that the repair of double strand breaks caused by ionizing radiation was inhibited by adenoviral proteins and led to autophagic cell death. Both subcutaneous models and intrapulmonary tumor models mimicking metastatic, aggressive disease were used in vivo. Virus efficacy was evaluated by intratumoral injections. Also, intravenous administration was evaluated to study the effectiveness in metastatic disease. Oncolytic adenovirus treatment led to significant tumor growth control and increased the survival rate of the mice. These results were further improved when oncolytic Ads were combined with radiation therapy. Oncolytic Ads expressing human sodium/iodide transporter (hNIS) as a transgene were evaluated for their oncolytic potency and for the functionality of hNIS in vitro and in vivo. Monitoring of viral replication was also assessed using different imaging modalities relative to clinical use. SPECT imaging of tumor-bearing mice was evaluated and combined with simultaneous CT-scanning to obtain important anatomical information on biodistribution, also in a three-dimensional form. It was shown that hNIS-expressing adenoviruses could harbour a bi-functional transgene allowing for localization and imaging of viral replication. Targeted radiotherapy was applied by systemic radioiodide administration and resulted in iodide accumulation into Ad-infected tumor. The combination treatment showed significantly enhanced antitumor efficacy in mice bearing prostate cancer tumors. In summary, the results presented above aim to provide new treatment modalities for castration resistant prostate cancer. Molecular insights were provided for better understanding of the benefits of combined radiation therapy and oncolytic adenoviruses, which will hopefully facilitate the translation of the approach into clinical use for humans.

Nainen, mies, rakkaus, seksi : Heterosuhteen kulku, kulttuurinen malli ja sitä selittävät diskurssit kahden omaelämäkerta-aineiston valossa

The subject matter of this study is the cultural knowledge concerning romantic male-female relationships in autobiographies written by so called ordinary Finnish men and women born between 1901 and 1965. The research data (98 autobiographies) is selected from two collections by the Finnish Literature Society s folklore archives in the early 1990 s. Autobiographies are cultural representations where negotiation of shared cultural models and personal meanings given to hetero-relationship is evident in an interesting manner. In this research I analyze autobiographies as a written folklore genre. Information concerning male-female relationships is being analyzed using theoretically informed close readings thematic analysis, intertextual reading and reflexive reading. Theoretical implications stem from cognitive anthropology (the idea of cultural models) and an adaptation of discourse theory inspired by Michel Foucault. The structure of the analysis follows the structure of the shared knowledge concerning romantic male-female relationship: the first phase of analysis presents the script of a hetero-relationship and then moves into the actual structure, the cultural model of a relationship. The components of the model of relationship are, as mentioned in the title of the research, woman, man, love and sex. The research shows that all the writers share this basic knowledge concerning a heterosexual relationship despite their age, background or gender. Also the conflicts described and experienced in the relationships of the writers were similar throughout the timespan of the early 1900 s to 1990 s: lack of love, inability to reconcile sexual desires, housework, sharing the responsibility of childcare and financial problems. The research claims that the conflicts in relationships are a major cause for the binary view on gender. When relationships are harmonious, there seems to be no need to see men and women as opposites. The research names five important discourses present in the meaning giving processes of autobiographers. In doing so, the stabile cultural model of male-female relationship widens to show the complexity and variation in data. In this way it is possible to detect some age and gender specific shifts and emphasis. The discourses give meaning to the components of the cultural model and determine the contents of womanhood, manhood, sexuality and love. The way these discourses are spread and their authority are different: the romantic discourse evident in the autobiographies appeal to the authority of love supreme love is the purpose of male-female relationship and it justifies sexuality. In this discourse sex can be the place for confluence of genders. The ideas of romantic love are widely spread in popular culture. Popular scientific discourse defines a relationship as a site to become a man and a woman either from a psychological or a biological point of view. Genders are seen as opposites. These ideas are often presented in media and their authority in science which is seen as infallible. The Christian discourse defines men and women: both should work for the benefit of the nuclear family under the undisputed authority of God. Marital love is based on Christian virtues and within marriage sexuality is acceptable. The discourse I ve named folk tradition defines women and men as guardians of home and offspring. The authority of folk tradition comes from universal truth based in experience and truths known to the mediators of this discourse grandparents, parents and other elders or peers. Societal discourse defines the hetero relationship as the mainstay of society. The authority in societal discourse stems from the laws and regulations that control relationship practices.

Essays on the Costs and Benefits of Large Shareholders in Corporate Governance (summary section only)

“Corporate governance deals with the ways in which suppliers of finance to firms assure themselves of getting a return on their investment” (Shleifer and Vishny (1997, p. 737). According to La Porta et al. (1999), research in corporate finance relevant for most countries should focus on the incentives and capabilities of controlling shareholders to treat themselves preferentially at the expense of minority shareholders. Accordingly, this thesis sets out to answer a number of research questions regarding the role of large shareholders in public firms that have received little attention in the literature so far. A common theme in the essays stems from the costs and benefits of individual large-block owners and the role of control contestability from the perspective of outside minority shareholders. The first essay empirically examines whether there are systematic performance differences between family controlled and nonfamily controlled firms in Western Europe. In contrast to the widely held view that family control penalizes firm value, the essay shows that publicly traded family firms have higher performance than comparable firms. In the second essay, we present both theoretical and empirical analysis on the effects of control contestability on firm valuation. Consistent with the theoretical model, the empirical results show that minority shareholders benefit from a more contestable control structure. The third essay explores the effects of individual large-block owners on top management turnover and board appointments in Finnish listed firms. The results indicate that firm performance is an important determinant for management and board restructurings. For certain types of turnover decisions the corporate governance structure influences the performance / turnover sensitivity. In the fourth essay, we investigate the relation between the governance structure and dividend policy in Finnish listed firms. We find evidence in support of the outcome agency model of dividends stating that lower agency conflicts should be associated with higher dividend payouts.

Corporate Governance in China (summary section only)

The negative relationship between economic growth and stock market return is not an anomaly according to evidence documented in many economies. It is argued that future economic growth is largely irrelevant for predicting future equity returns, since long-run equity returns depend mainly on dividend yields and the growth of per share dividends. The economic growth does result in a higher standard of living for consumers, but does not necessarily translate into higher returns for owners of the capital. The divergence in performance between the real sector and stock markets appears to support the above argument. However, this thesis strives to offer an alternative explanation to the apparent divergence within the framework of corporate governance. It argues that weak corporate governance standards in Chinese listed firms exacerbated by poor inventor protection results into a marginalized capital market. Each of the three essays in the thesis addresses one particular aspect of corporate governance on the Chinese stock market in a sequential way through gathering empirical evidence on three distinctive stock market activities. The first essay questions whether significant agency conflicts do exist by building a game on rights issues. It documents significant divergence in interests among shareholders holding different classes of shares. The second essay investigates the level of agency costs by examining value of control through constructing a sample of block transactions. It finds that block transactions that transfer ultimate control entail higher premiums. The third essay looks into possible avenues through which corporate governance standards could be improved by investigating the economic consequences of cross-listing on the Chinese stock market. It finds that, by adopting a higher disclosure standard through cross-listings, firms voluntarily commit themselves to reducing information asymmetry, and consequently command higher valuation than their counterparts.

The British Intervention in South Russia 1918-1920

Soon after the Bolshevik Revolution of 1917, a three-year civil war broke out in Russia. As in many other civil wars, foreign powers intervened in the conflict. Britain played a leading role in this intervention and had a significant effect on the course of the war. Without this intervention on the White side, the superiority of numbers in manpower and weaponry of the Bolsheviks would have quickly overwhelmed their opponents. The aim of this dissertation is to explain the nature and role of the British intervention on the southern, and most decisive, front of the Civil War. The political decision making in London is studied as a background, but the focus of the dissertation is on the actual implementation of the British policy in Russia. The British military mission arrived in South Russia in late 1918, and started to provide General Denikin s White army with ample supplies. General Denikin would have not been able to build his army of more than 200,000 men or to make his operation against Moscow without the British matériel. The British mission also organized the training and equipping of the Russian troops with British weapons. This made the material aid much more effective. Many of the British instructors took part in fighting the Bolsheviks despite the orders of their government. The study is based on primary sources produced by British departments of state and members of the British mission and military units in South Russia. Primary sources from the Whites, including the personal collections of several key figures of the White movement and official records of the Armed Forces of South Russia are also used to give a balanced picture of the course of events. It is possible to draw some general conclusions from the White movement and reasons for their defeat from the study of the British intervention. In purely material terms the British aid placed Denikin s army in a far more favourable position than the Bolsheviks in 1919, but other military defects in the White army were numerous. The White commanders were unimaginative, their military thinking was obsolete, and they were incapable of organizing the logistics of their army. There were also fundamental defects in the morale of the White troops. In addition to all political mistakes of Denikin s movement and a general inability to adjust to the complex situation in Revolutionary Russia, the Whites suffered a clear military defeat. In South Russia the Whites were defeated not because of the lack of British aid, but rather in spite of it.

Hyveiden harjoittaminen : edellytykset ja esteet

In the first half of the 20th century, most moral philosophers took the concept of virtue to be secondary to moral principles or emotions, though in various and mutually conflicting ways. In the early 1960s interest in the virtues was restored by the analytic philosophers Elizabeth Anscombe and Georg Henrik von Wright, the younger colleagues and friends of the late Wittgenstein. Later, Alasdair MacIntyre became a leading virtue ethicist. In 1981, MacIntyre introduced in After Virtue the concept of practices, which he based on the Aristotelian distinction between praxis and poiesis. This dissertation examines MacIntyre s characterization of the interconnectedness between practices and virtues, especially in relation to skills, education, and certain emotions. The primary position of the virtues is defended against the tendency in modern moral philosophy to overemphasize the role either of principles and rules or of emotions. The view according to which rational action and acting according to the virtues is best conceptualized as following rules or principles is criticized by arguments that are grounded by some Wittgensteinian observations, and that can be characterized as transcendental. Even if the virtues cannot be defined by, and are not based entirely on, emotions, the role of certain emotions on the learning and education of skills and virtues are studied more carefully than by MacIntyre. In the cases of resentment, indignation, and shame, the analysis of Peter Strawson is utilized, and in the case of regret, the analysis of Bernard Williams. Williams analysis of regret and moral conflict concludes in a kind of antirealism, which this study criticizes. Where education of practices and skills and the related reactive emotions are examined as conditions of learning and practicing the virtues, institutions and ideologies are examined as obstacles and threats to the virtues. This theme is studied through Karl Marx s conception of alienation and Karl Polanyi s historical and sociological research concerning the great transformation . The study includes six Finnish-published articles carrying the titles Our negative attitudes towards other persons , Authority and upbringing , Moral conflicts, regret and ethical realism , Practices and institutions , Doing justice as condition to communal action: a transcendental argument for justice as virtue , and Alienation from practices in capitalist society: Alasdair MacIntyre s Marxist Aristotelianism . The introductory essay sums up the themes of the articles and presents some central issues of virtue ethics by relating the classical Socratic questions to Aristotelian practical philosophy, as well as to current controversies in metaethics and moral psychology.

An Axiom of Military Law : Applicability of National Criminal Law to Military Personnel and Associated Civilians Abroad

States regularly deploy elements of their armed forces abroad. When that happens, the military personnel concerned largely remain governed by the penal law of the State that they serve. This extraterritorial extension of national criminal law, which has been treated as axiomatic in domestic law and ignored by international law scholarship, is the subject of this dissertation. The first part of the study considers the ambit of national criminal law without any special regard to the armed forces. It explores the historical development of the currently prevailing system of territorial law and looks at the ambit that national legal systems claim today. Turning then to international law, the study debunks the oddly persistent belief that States enjoy a freedom to extend their laws to extraterritorial conduct as they please, and that they are in this respect constrained only by some specific prohibitions in international law. Six arguments historical, empirical, ideological, functional, doctrinal and systemic are advanced to support a contrary view: that States are prohibited from extending the reach of their legal systems abroad, unless they can rely on a permissive principle of international law for doing so. The second part of the study deals specifically with State jurisdiction in a military context, that is to say, as applied to military personnel in the strict sense (service members) and various civilians serving with or accompanying the forces (associated civilians). While the status of armed forces on foreign soil has transformed from one encapsulated in the customary concept of extraterritoriality to a modern regulation of immunities granted by treaties, elements of armed forces located abroad usually do enjoy some degree of insulation from the legal system of the host State. As a corollary, they should generally remain covered by the law of their own State. The extent of this extraterritorial extension of national law is revealed in a comparative review of national legislation, paying particular attention to recent legal reforms in the United States and the United Kingdom two states that have sought to extend the scope of their national law to cover the conduct of military contractor personnel. The principal argument of the dissertation is that applying national criminal law to service members and associated civilians abroad is distinct from other extraterritorial claims of jurisdiction (in particular, the nationality principle or the protective principle of jurisdiction). The service jurisdiction over the armed forces has a distinct aim: ensuring the coherence and indivisibility of the forces and maintaining discipline. Furthermore, the exercise of service jurisdiction seeks to reduce the chances of the State itself becoming internationally liable for the conduct of its service members and associated civilians. Critically, the legal system of the troop-deploying State, by extending its reach abroad, seeks to avoid accountability gaps that might result from immunities from host State law.

Elämästä autofiktioksi : Lajitradition jäljillä Pirkko Saision romaanisarjassa Pienin yhteinen jaettava, Vastavalo ja Punainen erokirja

Pirkko Saisio's trilogy Pienin yhteinen jaettava (The Smallest Shared Dividend, 1998), Vastavalo (Against the Light, 2000), and Punainen erokirja (The Red Book of Separation, 2003), depicts the development of a masculine girl who at the end of the trilogy comes out as a homosexual women, a mother, and a writer. The main character is named Pirkko Saisio, and many of the events are picked from Saisio's real life. Nevertheless, the author wants the trilogy to be read as a novel, not a memoir. The present study analyses the generic elements of Saisio s trilogy and contextualizes the narrative identity that Saisio is creating in her fiction. Following Alastair Fowler s theory of genres as types without strict borders and a tendency to hybridity, the trilogy is linked to several genres. Serge Doubrovsky s genre concept of autofiction is the basis for the analysis: it explains the trilogy s borderline identity between autobiography and novel, and designates the main elements that render Saisio s autobiographical narrative into fiction. Both Doubrovsky and Saisio emphasize the role of the unconscious in writing, and at the same time stress the importance of a skilled composition. As well as autofiction, the trilogy is analyzed as a Bildungsroman, a confession and conversion narrative, a coming-out -narrative and a portrait-of-the-artist novel. Each genre is illuminated by its paradigmatic work: Wilhelm Meister s Apprenticeship by Goethe, The Confessions by St. Augustine, and The Well of Loneliness by Radclyffe Hall. The parallelisms between Saisio s trilogy and the typical plots of the genres and thematics of the classics show how the tradition works in Saisio s text. The thematic parallelisms highlight Saisio s concern for the conflicts that occur between an individual and the surrounding society, while the similarities in plots question the autobiographicality of Saisio s narrative but also clarify how Saisio refines the traditional genres. Read in the light of Saisio s trilogy, the classics are shown to have their gender-transgressive elements that the non-normative reader can identify with. Saisio s text also challenges universalizing claims about genre and gender. As a narrative of identity it follows the example of 1970s essentialistic coming-out stories, but at the same time depicts the notion of identity in a manner that manifests postmodern ideas about identity as multiple and ever-transforming. Keywords: autobiographicality, autofiction, identity narrative, genre research, Bildungsroman, conversion narrative, confession, coming-out story, a portrait-of-an-artist novel

After interpretation.

Using 58 audio recorded sessions of psychoanalysis (coming from two analysts and three patients) as data and conversation analysis as method, this paper shows how psychoanalysts deal with patients’ responses to interpretations. After the analyst offers an interpretation, the patient responds: at that point (in the “third position”), the analysts recurrently modify the tenor of the description from what it was in the patients’ responses. They intensify the emotional valence of the description, or they reveal layers of the patients’ experience other than those that the patient reported. Both are usually accomplished in an implicit, non-marked way, and they discreetly index possible opportunities for the patients to modify their understandings of the initial interpretation. Although the patients usually do not fully endorse these modifications, the data available suggests that during the sessions that follow, the participants do work with the aspects of patients’ experience that the analyst highlighted. In discussion, it is suggested that actions that the psychoanalysts produce in therapy, such as choices of turn design in third position, may be informed by working understanding of the minds and mental conflicts of individual patients, alongside the more general therapeutic model of mind they hold to.

Choosing the Arranged One, Arranging the Chosen One – Imagining an Indian Modernity: Reconciling Love, Marriage and Family On and Off the Screen

This is a study on the changing practices of kinship in Northern India. The change in kinship arrangements, and particularly in intermarriage processes, is traced by analysing the reception of Hindi popular cinema. Films and their role and meaning in people´s lives in India was the object of my research. Films also provided me with a methodology for approaching my other subject-matters: family, marriage and love. Through my discussion of cultural change, the persistence of family as a core value and locus of identity, and the movie discourses depicting this dialogue, I have looked for a possibility of compromise and reconciliation in an Indian context. As the primary form of Indian public culture, cinema has the ability to take part in discourses about Indian identity and cultural change, and alleviate the conflicts that emerge within these discourses. Hindi popular films do this, I argue, by incorporating different familiar cultural narratives in a resourceful way, thus creating something new out of the old elements. The final word, however, is the one of the spectator. The “new” must come from within the culture. The Indian modernity must be imaginable and distinctively Indian. The social imagination is not a “Wild West” where new ideas enter the void and start living a life of their own. The way the young women in Dehra Dun interpreted family dramas and romantic movies highlights the importance of family and continuity in kinship arrangements. The institution of arranged marriage has changed its appearance and gained new alternative modes such as love cum arranged marriage. It nevertheless remains arranged by the parents. In my thesis I have offered a social description of a cultural reality in which movies act as a built-in part. Movies do not work as a distinct realm, but instead intertwine with the social realities of people as a part of a continuum. The social imagination is rooted in the everyday realities of people, as are the movies, in an ontological and categorical sense. According to my research, the links between imagination and social life were not so much what Arjun Appadurai would call global and deterritorialised, but instead local and conventional.

Kansalaisuus työyhteisön arjessa : Maahanmuuttajien kertomuksia työelämästä

Citizenship in the everyday of a work community. Immigrants narratives of working life. Through globalisation and the mobility of workforce, citizenship has gained new forms, and the mere legal definition of citizenship no longer gives a comprehensive view of the citizenship of an individual. Also the social, cultural and financial dimensions of it are related to the concept of citizenship. In Finland, full citizenship is promoted, according to the Integration Act and social security system, by the requirement that immigrants should mainly get their livelihood through work. In my study I approach citizenship on four levels: the global, national, work community and private levels. In the study, the global has constituted the largest possible context, which refers to the local affects of global processes. The local and the global come together in the research in that globalisation is realised on the local level, i.e. in small communities such as work communities. The objective of the study is to examine how the citizenship of immigrants who live and work in Finland is constructed in the everyday life of a work community. The most central concept of the study is cultural script, which is based on prevailing forms of knowing, and which are constructed in different ways in different times and cultures. Conflicts of scripts in the working life and difficulties in understanding and applying them are in the centre of the study. In the study, the working life experiences of immigrants are approached through narrative research. The research material consists of the working life narratives of nine immigrants who live and work in Finland permanently. Each interviewee has been interviewed 2 4 times so the research material consists of 26 interviews. The material has been analysed from the points of view of perception, feeling and action. Deborah Tannen s and William Labov s as well as Matti Hyvärinen s method of expectancy analysis to locate cultural scripts has been utilised to organise the research material. In addition, David Herman s concepts of participatory roles and event types formed in narratives have been used in the analysis of the material. The basis in the analysis is that the world, events and experiences do not define the available processes; they are always culturally and individually anchored choices of the speaker and narrator. The most important results of the study are related to the gap between globalisation and everyday life. The discussion about the future need for workforce due to the changing population structure as well as about the benefits for national economy brought by internationalisation has continued in Finland for years. However, the working life narratives of the immigrants interviewed for the study show that an average citizen and member of a work community does not immediately encounter the macro level benefits in, for example, the mobility of workforce. In most of the working life narratives there was a point in speaking and saying, in which the immigrant worker either dares to speak or falls silent. Sometimes the courage to speak was related to language skills but more to the courage to be seen and to be part of a Finnish work community. Other workers that either speak their colleague with an immigrant background into a part of their work community or marginalise the colleague with their silence have an important role in a Finnish work community. In several working life narratives, the script of the Finnish working life and work community, the way to work, was opened to the immigrant and the so-called script exchange did not take place. The study shows that working life experiences and inclusion and exclusion built on the working life have an important role in the construction of active citizenship. The detailed analysis of the working life experience narratives gives new, relevant research data about citizenship as inclusion.

Towards Explaining the Tasks and Roles of the Boards of Directors

While previous research has helped to improve our understanding of corporate governance and boards of directors, less is known about the factors that affect boards’ tasks and roles and directors’ motivation and engagement. This requires knowledge of how board decisions are being made and the internal and external factors that affect the decision-making process. Large inferential leaps have been made from board demographics to firm performance with equivocal results. This thesis concentrates on how the institutional, behavioral and social identification factors impact the enactment of board roles and tasks. Data used in this thesis were collected in 2009 through a mailed survey to Finnish large and middle-sized corporations. The findings suggest that firstly, the national context of an organization is reflected in board roles and shapes how and for what reasons the board roles are carried out; secondly, the directors’ human and external social capital invariably impacts their engagement in board tasks and that conflicts among directors moderate those relationships; finally, directors’ identification with the organization, its shareholders and its customers affect the directors’ involvement in board tasks. By addressing the impact of organisational context, board-internal behaviour and social identification of board members on board roles and tasks, this thesis firstly complements the shareholder supremacy view as the only reason for the board’s involvement with specific tasks; secondly questions the existence of the board as separate from its institutional context; and thirdly questions the view that a board is a ‘black box’, subject to a selection of input demographic variables and producing quantifiable results. The thesis demonstrates that boards are complex organisational bodies, which involve much interaction among board members. Director behaviour and its influence on board decision making is an important determinant of board tasks and boards are likely subjected to inter-group tensions and are susceptible to the influence of internal and external social forces.

Unraveling the helix of change : An activity-theoretical study of health care change efforts and their consequences

M.A. (Educ.) Anu Kajamaa from the University of Helsinki, Center for Research on Activity, Development and Learning (CRADLE), examines change efforts and their consequences in health care in the public sector. The aim of her academic dissertation is, by providing a new conceptual framework, to widen our understanding of organizational change efforts and their consequences and managerial challenges. Despite the multiple change efforts, the results of health care development projects have not been very promising, and many developmental needs and managerial challenges exist. The study challenges the predominant, well-framed health care change paradigm and calls for an expanded view to explore the underlying issues and multiplicities of change efforts and their consequences. The study asks what kind of expanded conceptual framework is needed to better understand organizational change as transcending currently dominant oppositions in management thinking, specifically in the field of health care. The study includes five explorative case studies of health care change efforts and their consequences in Finland. Theory and practice are tightly interconnected in the study. The methodology of the study integrates the ethnography of organizational change, a narrative approach and cultural-historical activity theory. From the stance of activity theory, historicity, contradictions, locality and employee participation play significant roles in developing health care. The empirical data of the study has mainly been collected in two projects, funded by the Finnish Work Environment Fund. The data was collected in public sector health care organizations during the years 2004-2010. By exploring the oppositions between distinct views on organizational change and the multi-site, multi-level and multi-logic of organizational change, the study develops an expanded, multidimensional activity-theoretical framework on organizational change and management thinking. The findings of the study contribute to activity theory and organization studies, and provide information for health care management and practitioners. The study illuminates that continuous development efforts bridged to one another and anchored to collectively created new activity models can lead to significant improvements and organizational learning in health care. The study presents such expansive learning processes. The ways of conducting change efforts in organizations play a critical role in the creation of collective new practices and tools and in establishing ownership over them. Some of the studied change efforts were discontinuous or encapsulated, not benefiting the larger whole. The study shows that the stagnation and unexpected consequences of change efforts relate to the unconnectedness of the different organizational sites, levels and logics. If not dealt with, the unintended consequences such as obstacles, breaks and conflicts may stem promising change and learning processes.

The German Military Entrepreneur Ernst von Mansfeld and His Conduct of Asymmetrical Warfare in the Thirty Years War

The dissertation examines aspects of asymmetrical warfare in the war-making of the German military entrepreneur Ernst von Mansfeld during his involvement in the Thirty Years War. Due to the nature of the inquiry, which combines history with military-political theory, the methodological approach of the dissertation is interdisciplinary. The theoretical framework used is that of asymmetrical warfare. The primary sources used in the dissertation are mostly political pamphlets and newsletters. Other sources include letters, documents, and contemporaneous chronicles. The secondary sources are divided into two categories, literature on the history of the Thirty Years War and textbooks covering the theory of asymmetrical warfare. The first category includes biographical works on Ernst von Mansfeld, as well as general histories of the Thirty Years War and seventeenth-century warfare. The second category combines military theory and political science. The structure of the dissertation consists of eight lead chapters, including an introduction and conclusion. The introduction covers the theoretical approach and aims of the dissertation, and provides a brief overlook of the sources and previous research on Ernst von Mansfeld and asymmetrical warfare in the Thirty Years War. The second chapter covers aspects of Mansfeld s asymmetrical warfare from the perspective of operational art. The third chapter investigates the illegal and immoral aspects of Mansfeld s war-making. The fourth chapter compares the differing methods by which Mansfeld and his enemies raised and financed their armies. The fifth chapter investigates Mansfeld s involvement in indirect warfare. The sixth chapter presents Mansfeld as an object and an agent of image and information war. The seventh chapter looks into the counter-reactions, which Mansfeld s asymmetrical warfare provoked from his enemies. The eighth chapter offers a conclusion of the findings. The dissertation argues that asymmetrical warfare presented itself in all the aforementioned areas of Mansfeld s conduct during the Thirty Years War. The operational asymmetry arose from the freedom of movement that Mansfeld enjoyed, while his enemies were constrained by the limits of positional warfare. As a non-state operator Mansfeld was also free to flout the rules of seventeenth-century warfare, which his enemies could not do with equal ease. The raising and financing of military forces was another source of asymmetry, because the nature of early seventeenth-century warfare favoured private military entrepreneurs rather than embryonic fiscal-military states. The dissertation also argues that other powers fought their own asymmetrical and indirect wars against the Habsburgs through Mansfeld s agency. Image and information were asymmetrical weapons, which were both aimed against Mansfeld and utilized by him. Finally, Mansfeld s asymmetrical threat forced the Habsburgs to adapt to his methods, which ultimately lead to the formation of a subcontracted Imperial Army under the management and leadership of Albrecht von Wallenstein. Therefore Mansfeld s asymmetrical warfare ultimately paved way for the kind of state-monopolized, organised, and symmetrical warfare that has prevailed from 1648 onwards. The conclusion is that Mansfeld s conduct in the Thirty Years War matched the criteria for asymmetrical warfare. While traditional historiography treated Mansfeld as an anomaly in the age of European state formation, his asymmetrical warfare has begun to bear resemblance to the contemporary conflicts, where nation states no longer hold the monopoly of violence.

Impaired conflict monitoring in Parkinson's disease patients during an oculomotor redirect task

Fallibility is inherent in human cognition and so a system that will monitor performance is indispensable. While behavioral evidence for such a system derives from the finding that subjects slow down after trials that are likely to produce errors, the neural and behavioral characterization that enables such control is incomplete. Here, we report a specific role for dopamine/basal ganglia in response conflict by accessing deficits in performance monitoring in patients with Parkinson's disease. To characterize such a deficit, we used a modification of the oculomotor countermanding task to show that slowing down of responses that generate robust response conflict, and not post-error per se, is deficient in Parkinson's disease patients. Poor performance adjustment could be either due to impaired ability to slow RT subsequent to conflicts or due to impaired response conflict recognition. If the latter hypothesis was true, then PD subjects should show evidence of impaired error detection/correction, which was found to be the case. These results make a strong case for impaired performance monitoring in Parkinson's patients.