Proliferating cell nuclear antigen (PCNA) is a 36 kD nuclear protein associated with the cell cycle. A monoclonal antibody, PC10, that recognizes a fixation and processing resistant epitope has been used to investigate its tissue distribution. Nuclear PCNA immunoreactivity is found in the proliferative compartment of normal tissues. PCNA immunoreactivity is induced in lectin stimulated peripheral blood mononuclear cells in parallel with bromodeoxyuridine incorporation and the number of cells with PCNA immunoreactivity is reduced by induction of differentiation in HL60 cells. In non-Hodgkin's lymphomas a linear relation between Ki67 and PCNA staining was demonstrated. These data suggest that in normal tissues and lymphoid neoplasms, PCNA immunolocalization can be used as an index of cell proliferation. However, in some forms of neoplasia, including breast and gastric cancer and in vitro cell lines, the simple relation between PCNA expression and cell proliferation is lost. In some breast and pancreatic tumours there is apparent deregulation of PCNA with increased expression in tissues adjacent to the tumours. The over-expression in some tumours and in adjacent morphologically normal tissue may represent autocrine or paracrine growth factor influence on PCNA gene expression.

Immunohistochemical methods using antibodies to cell cycle-related antigens may be used as a means of assessing various aspects of proliferation in tissue, and have the important advantage of preserving the spatial orientation of proliferating cells in histological sections. Currently, the most widely available antibodies for this purpose are antibodies to bromodeoxyuridine (BrdU), Ki67 and antibodies to proliferating cell nuclear antigen (PCNA). BrdU is a thymidine analogue incorporated during the S phase of the cell cycle, which can be introduced by 'in vitro' incubation, and monoclonal antibodies are available to display its localization. Ki67 demonstrates a nuclear antigen expressed in all phases of the cell cycle, except G0 and early G1, but can only be applied to frozen tissue. PCNA is a nuclear antigen which is essential for DNA synthesis, two commercially available antibodies to PCNA work in paraffin-embedded tissue, but may have different staining characteristics under different conditions of fixation. The main advantages and disadvantages of these different techniques are discussed, together with their main applications to date.

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PCNA is a nuclear protein that is synthesized in late G1 and S phases of the cell cycle and is, therefore, correlated with the cell proliferative state. A new monoclonal antibody (PC10) to genetically engineered PCNA has been shown to label proliferating cells in formalin-fixed paraffin-embedded normal human tissues. Previous studies in lymphomas, using various markers of cell proliferation, have shown a strong correlation between indices of cell proliferation and histological grade. These studies have shown that within each histological subtype there is often a wide range of proliferative indices and that these may be of some prognostic significance. Thirty-one gastrointestinal lymphomas were studied. Our results show that there is a good correlation between PC10 index and histological grade of tumour (0.01 P greater than P greater than 0.001) and also a significant relationship between PC10 index and S+G2+M phase fraction as measured by flow cytometric analysis (r2 = 0.62; P less than 0.01). Twenty-three cases were available for survival analysis. In these cases a high PC10 score correlated with poor survival (P = 0.04). Based on this series, it appears that there is a significant relationship between PC10 index and histological grade, and between PC10 index and S+G2+M phase as measured by flow cytometric analysis. In addition, our results suggest that a high PC10 index is an adverse prognostic factor in primary gastrointestinal lymphoma.

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Objective: The purpose of this meta-analytic review is to examine the role of three work environment support variables (i.e., peer, supervisor, and organizational support) in training transfer and sustainment or long-term use of learned knowledge, skills, and attitudes (KSAs). Background: Estimates demonstrate that little training is transferred to the job, wasting billions in organizational spending each year and resulting in significant loss to safety and individual and team performance. Prior research shows the importance of a supportive work environment to facilitating transfer; however, we know little of the relative importance of specific support variables. This study seeks to examine the unique roles of distinct support variables in training transfer. Method: A meta-analysis was conducted with multiple regressions to answer three primary research questions. Results: All work environment support variables demonstrate moderate and positive correlations with transfer of training. Furthermore, multiple regressions demonstrate that each factor of the work environment explains unique variance as a predictor, with the model accounting for 32% of transfer and peer support accounting for most of R2. Motivation to transfer mediates the relationship between all three work environment support variables and transfer. Furthermore, three support variables are positively related to sustainment, with peer and supervisor support showing the strongest relationships. Conclusion: Findings illuminate the relative contribution of peer, supervisor, and organizational support to transfer and sustainment of training. As transfer continues to be an important yet understudied measure of the effectiveness of workplace training, these findings hold implications for both research and practice.

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Background: Safe and effective patient care depends on the teamwork of multidisciplinary healthcare professionals. Unfortunately, the field currently lacks an evidence-based framework for effective teamwork that can be incorporated into medical education and practice across health professions. We introduce a comprehensive framework for team effectiveness. Common challenges to teamwork in healthcare are identified along with evidence-based strategies for overcoming them.Methods: The framework was developed in four steps: 1) grounding in the existing team science literature, 2) semi-structured interviews (N = 13), 3) thematic analysis and initial framework development, and 4) revision of the framework through input from healthcare professionals representative of different functions across the healthcare system (N = 13). A diagnostic tool consisting of one survey item per team competency was developed to complement the framework. The survey was then administered to healthcare teams across clinical and administrative functions (N = 10 teams, 96 individuals), and results were compiled and then used to conduct debriefs with individual team members and teams. A set of common teamwork challenges were identified using the survey and qualitative data. Qualitative data was analyzed to explore the unique ways these challenges manifest in both clinical and administrative teams.Results: The five most common challenges that face healthcare teams relate to accountability, conflict management, decision-making, reflecting on progress, and coaching. These challenges were similar across both clinical and administrative team types. Based on the authors' collective experience designing and implementing Team Development Interventions (TDIs), strategies for managing each challenge are provided.Conclusions: The proposed framework is unique in two ways. First, it's generally applicable across the many types of teams that contribute to the quality and safety of patient care. Second, the levels of the framework build upon each other to contribute to the development of the ideal team states. The framework and accompanying strategies can provide guidance for where and how to target developmental efforts.