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.

DNA damage recognition in the normal epithelium of human prostate and seminal vesicles

Prostate cancer is one of the most prevalent cancer types in men. The development of prostate tumors is known to require androgen exposure, and several pathways governing cell growth are deregulated in prostate tumorigenesis. Recent genetic studies have revealed that complex gene fusions and copy - number alterations are frequent in prostate cancer, a unique feature among solid tumors. These chromosomal aberrations are though to arise as a consequence of faulty repair of DNA double strand breaks (DSB). Most repair mechanisms have been studied in detail in cancer cell lines, but how DNA damage is detected and repaired in normal differentiated human cells has not been widely addressed. The events leading to the gene fusions in prostate cancer are under rigorous studies, as they not only shed light on the basic pathobiologic mechanisms but may also produce molecular targets for prostate cancer treatment and prevention. Prostate and seminal vesicles are part of the male reproductive system. They share similar structure and function but differ dramatically in their cancer incidence. Approximately fifty primary seminal vesicle carcinomas have been reported worldwide. Surprisingly, only little is known on why seminal vesicles are resistant to neoplastic changes. As both tissues are androgen dependent, it is a mystery that androgen signaling would only lead to tumors in prostate tissue. In this work, we set up novel ex vivo human tissue culture models of prostate and seminal vesicles, and used them to study how DNA damage is recognized in normal epithelium. One of the major DNA - damage inducible pathways, mediated by the ATM kinase, was robustly activated in all main cell types of both tissues. Interestingly, we discovered that secretory epithelial cells had less histone variant H2A.X and after DNA damage lower levels of H2AX were phosphorylated on serine 139 (γH2AX) than in basal or stromal cells. γH2AX has been considered essential for efficient DSB repair, but as there were no significant differences in the γH2AX levels between the two tissues, it seems more likely that the role of γH2AX is less important in postmitotic cells. We also gained insight into the regulation of p53, an important transcription factor that protects genomic integrity via multiple mechanisms, in human tissues. DSBs did not lead to a pronounced activation of p53, but treatments causing transcriptional stress, on the other hand, were able to launch a notable p53 response in both tissue types. In general, ex vivo culturing of human tissues provided unique means to study differentiated cells in their relevant tissue context, and is suited for testing novel therapeutic drugs before clinical trials. In order to study how prostate and seminal vesicle epithelial cells are able to activate DNA damage induced cell cycle checkpoints, we used primary cultures of prostate and seminal vesicle epithelial cells. To our knowledge, we are the first to report isolation of human primary seminal vesicle cells. Surprisingly, human prostate epithelial cells did not activate cell cycle checkpoints after DSBs in part due to low levels of Wee1A, a kinase regulating CDK activity, while primary seminal vesicle epithelial cells possessed proficient cell cycle checkpoints and expressed high levels of Wee1A. Similarly, seminal vesicle cells showed a distinct activation of the p53 - pathway after DSBs that did not occur in prostate epithelial cells. This indicates that p53 protein function is under different control mechanisms in the two cell types, which together with proficient cell cycle checkpoints may be crucial in protecting seminal vesicles from endogenous and exogenous DNA damaging factors and, as a consequence, from carcinogenesis. These data indicate that two very similar organs of male reproductive system do not respond to DNA damage similarly. The differentiated, non - replicating cells of both tissues were able to recognize DSBs, but under proliferation human prostate epithelial cells had deficient activation of the DNA damage response. This suggests that prostate epithelium is most vulnerable to accumulating genomic aberrations under conditions where it needs to proliferate, for example after inflammatory cellular damage.