Elucidating the role of mesenchymal stem cell participation in the tumor microenvironment

To meet the requirements for rapid tumor growth, a complex array of non-neoplastic vascular, fibroblastic, and immune cells are recruited to the tumor microenvironment. Understanding the origin, composition, and mechanism(s) for recruitment of these stromal components will help identify areas for therapeutic intervention. Previous findings have suggested that ex-vivo expanded bone marrow-derived MSC home to the sites of tumor development, responding to inflammatory signals and can serve as effective drug delivery vehicles. Therefore, we first sought to fully assess conditions under which MSC migrate to and incorporate into inflammatory microenvironments and the consequences of modulated inflammation. MSC delivered to animals bearing inflammatory insults were monitored by bioluminescence imaging and displayed specific tropism and selective incorporation into all tumor and wound sites. These findings were consistent across routes of tumor establishment, MSC administration, and immunocompetence. MSC were then used as drug delivery vehicles, transporting Interferon β to sites of pancreatic tumors. This therapy was effective at inhibiting pancreatic tumor growth under homeostatic conditions, but inhibition was lost when inflammation was decreased with CDDO-Me combination treatment. Next, to examine the endogenous tumor microenvironment, a series of tissue transplant experiments were carried out in which tissues were genetically labeled and engrafted in recipients prior to tumor establishment. Tumors were then analyzed for markers of tumor associated fibroblasts (TAF): α-smooth muscle actin (α-SMA), nerve glia antigen 2 (NG2), fibroblast activation protein (FAP), and fibroblast specific protein (FSP) as well as endothelial marker CD31 and macrophage marker F4/80. We determined the majority of α-SMA+, NG2+ and CD31+ cells were non-bone marrow derived, while most FAP+, FSP+, and F4/80+ cells were recruited from the bone marrow. In accord, transplants of prospectively isolated BM MSC prior to tumor development indicated that these cells were recruited to the tumor microenvironment and co-expressed FAP and FSP. In contrast, fat transplant experiments revealed recruited fat derived cells co-expressed α-SMA, NG2, and CD31. These results indicate TAF are a heterogeneous population composed of subpopulations with distinct tissues of origin. These models have provided a platform upon which further investigation into tumor microenvironment composition and tests for candidate drugs can be performed. ^

A study of nurses' perceptions of and participation in the resolution of treatment dilemmas for critically ill newborns

This study was an exploratory investigation of variables which are associated with neonatal intensive care nurses' perceptions of and participation in life-sustaining treatment decisions for critically ill newborns. The primary purpose of the research was to examine the extent to which assessment of infants' physical and mental prognoses, parents' preferences regarding treatment, and legal consequences of non-treatment influence nurses' recommendations about life-saving treatment decisions for handicapped newborns. Secondly, the research explored the extent and nature of nurses' reported participation in the resolution of treatment dilemmas for these critically ill newborns. The framework of the study draws upon the work of Crane (1977), Blum (1980), and Pearlman (1982) who have explored the sociological context of decision-making with critical care patients.^ Participants in the study were a volunteer sample of eighty-three registered nurses who were currently working in neonatal intensive care units in five large urban hospitals in Texas. Data were collected through the use of intensive interviews and case study questionnaires. Results from the study indicate that physical and mental prognoses as well as parent preferences and concerns about legal liability are related to nurses' treatment recommendations, but their levels of significance vary according to the type of handicapping condition and whether the treatment questions are posed in terms of initiating aggressive therapy or withdrawing aggressive therapy.^ The majority of nurses reported that the extent of their participation in formal decision-making regarding handicapped newborns was fairly minimal although they provide much of the definitive data used to make decisions by physicians and parents. There was substantial evidence that nurse respondents perceive their primary role as advocates for critically ill newborns, and believe that their involvement in the resolution of treatment dilemmas should be increased. ^

Analysis of participation in the federally mandated coal workers' health surveillance program

The Federal Coal Mine Health and Safety Act of 1969 required that periodic chest radiographs be offered to underground coal miners to protect the miners from the development of Coal Workers' Pneumoconiosis (CWP) and progression of the disease to progressive massive fibrosis (PMF). These examinations are administered by the National Institute for Occupational Safety and Health (NIOSH) through the Coal Workers' Health Surveillance Program (CWHSP). The mine operator is required to provide each miner with the opportunity to have the chest radiograph at no cost to the miner.^ Three rounds of examinations have been conducted since 1969 and the fourth is underway. The decrease in participation over rounds is of great concern if the incidence and progression of CWP are to be understood and controlled.^ This study developed rates of participation for each of 558 West Virginia underground coal mines who submitted or had NIOSH assigned plans for making chest radiographs available during the third round, July 1978 through December 1980. These rates were analyzed in relation to desired levels of participation and to reinforcing, predisposing and enabling factors presumed to affect rates of participation in disease prevention and surveillance programs.^ Two reinforcing factors, size of mine and inclusion of the mine in the National Coal Study (NCS) epidemiology research program, and the enabling factor, use of an on-site radiograph facility, demonstrated highly significant relationships to participation rates.^ The major findings of the study were: (1) Participation in the CWHSP is even lower than previously estimated; (2) CWHSP program evaluation is not systematic and program data base is not complete and comprehensive; and (3) NIOSH program policy is not clear and administration of the CWHSP is fragmented and lacks adequate fiscal and personnel resources. ^

Improving pregnancy prevention in the Austin Independent School District: Student participation in the development of social marketing media

Pregnancy prevention is an important goal of the Austin Independent School District (AISD), but present activity is limited to utilizing a single curriculum. To effectively prevent pregnancy, a diverse range of programs and activities is needed—including media and social marketing. This project (1) reviews literature to identify best practices and characteristics of effective pregnancy prevention programs for AISD, (2) reports on the results of meetings that gathered recommendations for effective channels and media messages for pregnancy prevention among high school students in Central Texas, and (3) presents samples of social marketing media products developed for pregnancy prevention that can be used by AISD.^

Organizational perspectives on the management and evaluation of large -scale multicenter controlled clinical trials: An exploratory study of participation in the beta -blocker heart attack trial

A review of literature related to appointment-keeping served as the basis for the development of an organizational paradigm for the study of appointment-keeping in the Beta-blocker Heart Attack Trial (BHAT). Features of the organizational environment, demographic characteristics of BHAT enrollees, organizational structure and processes and previous organizational performance variables were measured so as to provide exploratory information relating to the appointment-keeping behavior of 3,837 participants enrolled at thirty-two Clinical Centers. Results suggest that the social context of individual behavior is an important consideration for the understanding of patient compliance. In particular, the degree to which previous organizational performance--as measured by obtaining recruitment goals--and the ability to utilize resources had particularly strong bivariate associations with appointment-keeping. Implications for future theory development, research and practical implications were provided as was a suggestion for the development of multidisciplinary research efforts conducted within the context of Centers for the study and application of adherence behaviors. ^

Q method factor analysis of stakeholder social perspectives of the effectiveness of Environmental Impact Assessment public participation in the Western Cape, South Africa

Public participation is an integral part of Environmental Impact Assessment (EIA), and as such, has been incorporated into regulatory norms. Assessment of the effectiveness of public participation has remained elusive however. This is partly due to the difficulty in identifying appropriate effectiveness criteria. This research uses Q methodology to discover and analyze stakeholder's social perspectives of the effectiveness of EIAs in the Western Cape, South Africa. It considers two case studies (Main Road and Saldanha Bay EIAs) for contextual participant perspectives of the effectiveness based on their experience. It further considers the more general opinion of provincial consent regulator staff at the Department of Environmental Affairs and the Department of Planning (DEA&DP). Two main themes of investigation are drawn from the South African National Environmental Management Act imperative for effectiveness: firstly, the participation procedure, and secondly, the stakeholder capabilities necessary for effective participation. Four theoretical frameworks drawn from planning, politics and EIA theory are adapted to public participation and used to triangulate the analysis and discussion of the revealed social perspectives. They consider citizen power in deliberation, Habermas' preconditions for the Ideal Speech Situation (ISS), a Foucauldian perspective of knowledge, power and politics, and a Capabilities Approach to public participation effectiveness. The empirical evidence from this research shows that the capacity and contextual constraints faced by participants demand the legislative imperatives for effective participation set out in the NEMA. The implementation of effective public participation has been shown to be a complex, dynamic and sometimes nebulous practice. The functional level of participant understanding of the process was found to be significantly wide-ranging with consequences of unequal and dissatisfied stakeholder engagements. Furthermore, the considerable variance of stakeholder capabilities in the South African social context, resulted in inequalities in deliberation. The social perspectives revealed significant differences in participant experience in terms of citizen power in deliberation. The ISS preconditions are highly contested in both the Saldanha EIA case study and the DEA&DP social perspectives. Only one Main Road EIA case study social perspective considered Foucault's notion of governmentality as a reality in EIA public participation. The freedom of control of ones environment, based on a Capabilities approach, is a highly contested notion. Although agreed with in principle, all of the social perspectives indicate that contextual and capacity realities constrain its realisation. This research has shown that Q method can be applied to EIA public participation in South Africa and, with the appropriate research or monitoring applications it could serve as a useful feedback tool to inform best practice public participation.

Increasing popular participation in the treaty-making process : the legislative process of Section 190 of the 2007 Constitution of Thailand

Historically, the authority to conclude international treaties was exclusively exercised by administrative bodies (or the chief of state). However, recent studies pointed out that the present legislative bodies have come to play a more active role through ratification or the review of treaties in European and American countries. Harrington (2005) studied judicial reform in British dominions and criticized the past executive-dominant treaty-making process as a “democratic deficit” due to a fear that under this system the nation might be bound by international agreements for which a consensus had not been obtained. These studies indicated that people’s participation in the treaty-making process has increased on a global basis, but neither of them provides sufficient descriptive evidence regarding why and how such procedures were established. The present paper therefore attempts to solve these questions by analyzing the legislative and political process of the treaty-making procedure reform in Thailand’s 2007 constitution as a case study.