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There is growing interest in tissue procurement for cancer research through autopsy. Establishing an autopsy/tissue donation programme for breast cancer research within an academic medical centre in the United States requires consideration, planning, multi-departmental collaboration and labour-intensive maintenance. It is the purpose of this paper to outline the necessary considerations in implementing and maintaining a tissue donation and autopsy programme within a breast cancer centre at a comprehensive cancer centre. Considerations of programme planning include: patient engagement, the recruitment of patients and families into the programme, the role and scope of work of the clinical coordinator, regulatory issues and the coordination with both pathology and the research team at time of death and autopsy/tissue donation. All aspects of the tissue donation/rapid autopsy programme development and implementation are discussed and illustrated through case study. An Autopsy/ Tissue Donation for breast cancer research can be successfully developed and implemented.

A pesquisa comparativa entre o pensamento de Freire e Grundtvig foi realizada por meio de estudos de casos de praticas que se reconheciam como freiriana e grundtviguiana, respectivamente. Apesar de viverem em seculos diferentes, ambos atuaram no campo da Educacao Popular de Jovens e Adultos, aqui definida como uma diversidade de praticas sociais relacionadas a producao e a circulacao de conhecimentos, experiencias e 10 valores voltados a emancipacao de jovens e adultos dos setores populares. A pergunta principal que orientou o projeto foi: quais sao as similaridades e as diferencas entre estes dois pedagogos no campo da educacao popular de jovens e adultos?

Background: Women with metastatic breast cancer (MBC) experience unique symptom management and psychosocial needs due to aggressive, yet palliative treatment with a progressive, chronic illness. Objective: This article describes the effect of a quality improvement project for coordination of supportive care in MBC. Program evaluations included referral rates for supportive services, patient-reported outcomes of symptom distress, generalized anxiety, and overall well-being. Design: An interdisciplinary Support, Education and Advocacy Program (MBC-SEA) was developed. The 1-hour, weekly, patient review included collaborative assessments to determine needs for social service, psychological counseling, and palliative care. A prospective pre- and postexperimental cohort design with convenience sampling was used. Analysis was conducted with paired t test analysis of pre- and postimplementation outcomes. Setting/Participants: Program outcomes of 118 women with MBC visiting an urban outpatient breast cancer clinic during September 2016 to November 2016 (pre) and January 2017 to March 2017 (post) were evaluated. Measurements: Referral rates to social work and palliative care, symptom, anxiety, and overall well-being scores. Results: Following program implementation, referrals to palliative care and social work supportive services increased significantly including patient-reported outcomes symptom distress scores mean difference 1.4 (95% confidence interval [CI]: 0.4306-2.6428), P = .004; generalized anxiety scores mean difference 1.5 (95% CI: 0.5406-2.5781), P = .003; and overall well-being mean difference of −0.7 (95% CI: −1.3498 to −0.0570), P = .03. Conclusions: Purposeful nurse-led assessment for social service and palliative care needs increases referrals with improvement in patient-reported outcomes.

Education philosopher Wilfred Carr points to the importance of engagement in the debates on the central issues in education, but not about education, rather for education. In this essay, we extend this position into the realm of management education by critiquing the disappointing outcomes of traditional approaches to teaching and learning, that is, spoon-feeding. We build on the imperative of enhancing student development through scholarly teaching that focuses on what we ask students to do. Our reflections derive from the disappointing results of an assignment asking students to articulate their learning by making claims to knowledge. Our interpretation argues for the need for reflexive practice by faculty as well as a systemic focus on developing students as more sophisticated “knowers,” especially in the management classroom.

Increasing knowledge concerning the biology of hematologic malignancies as well as the role of the immune system in the control of these diseases has led to the development and approval of immunotherapies that are resulting in impressive clinical responses. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a hematologic malignancy Cancer Immunotherapy Guidelines panel consisting of physicians, nurses, patient advocates, and patients to develop consensus recommendations for the clinical application of immunotherapy for patients with multiple myeloma, lymphoma, and acute leukemia. These recommendations were developed following the previously established process based on the Institute of Medicine’s clinical practice guidelines. In doing so, a systematic literature search was performed for high-impact studies from 2004 to 2014 and was supplemented with further literature as identified by the panel. The consensus panel met in December of 2014 with the goal to generate consensus recommendations for the clinical use of immunotherapy in patients with hematologic malignancies. During this meeting, consensus panel voting along with discussion were used to rate and review the strength of the supporting evidence from the literature search. These consensus recommendations focus on issues related to patient selection, toxicity management, clinical endpoints, and the sequencing or combination of therapies. Overall, immunotherapy is rapidly emerging as an effective therapeutic strategy for the management of hematologic malignances. Evidence-based consensus recommendations for its clinical application are provided and will be updated as the field evolves. Electronic supplementary material The online version of this article (doi:10.1186/s40425-016-0188-z) contains supplementary material, which is available to authorized users.

In this article, we argue for advancing grounded curricula, which explicitly link theory and pedagogy, and executing them in authentic and multidisciplinary settings as a means to facilitate student growth into integrative learners. We describe the development of a student-centered learning experience that combines elements of critical management education, situated learning, and design thinking. The commonalities between a critically based pedagogy and design thinking create a context for collaboration that enables students to acquire attributes consistent with integrative learners: critical reflection, multiliteracy, the ability to negotiate identity, engage in constructive critique, become skilled in knowledge transformation, and create tangible and implementable outcomes. Drawing from 13 years of pedagogical experimentation, this article contributes to the domain of management education by providing greater specification to the concept of integrative learning, as well as articulating a novel and effective pedagogy based in design thinking. We present our story in three acts, showing how our methodology can enable transformative student learning and offer faculty invigorating teaching experiences.

Purpose: Regulatory CD4+CD25highFoxp3+ T cells (Treg) control peripheral immune tolerance. Patients with cancer, including those with hematologic malignancies, have elevated numbers of Treg in the peripheral circulation and in tumor tissues. However, mechanisms of suppression and clinical significance of Treg, especially in patients with acute myelogenous leukemia (AML), has not been well defined.Experimental Design: We prospectively evaluated the phenotype, function, and mechanisms of suppression used by Treg in newly diagnosed untreated AML patients. The relationship between the frequency of circulating Treg and the disease status as well as treatment outcome was also evaluated.Results: The percentage of circulating Treg was higher (P < 0.0001) and their phenotype was distinct in AML patients relative to normal controls. Suppression mediated by Treg coincubated with proliferating autologous responder cells was also higher (P < 0.001) in AML than that mediated by control Treg. Using Transwell inserts, we showed that interleukin-10 and transforming growth factor-β1 production as well as cell-to-cell contact were necessary for Treg-mediated suppression. Also, the pretreatment Treg frequency predicted response to chemotherapy. Unexpectedly, patients who achieved complete remission still had elevated frequency of Treg, which mediated high levels of suppressor activity.Conclusions: Treg accumulating in the peripheral circulation of AML patients mediate vigorous suppression via contact-dependent and contact-independent mechanisms. Patients with lower Treg frequency at diagnosis have a better response to induction chemotherapy. During the post-induction period, the Treg frequency and suppressive activity remain elevated in complete remission, suggesting that Treg are resistant to conventional chemotherapy.

This article employs a critical realist perspective to contextualize management education, including the MBA, and facilitate debate on the prospects for its reinvention. Two decades of substantive management education critique has not resulted in any fundamental change in models of content and process used to educate managers. We argue this is a matter of ontology and discuss the advantages of critical realist ontology for addressing this issue. A critical realist analysis identifies the generative mechanisms at work that both necessitate and constrain reinvention. We argue that one generative mechanism in particular, a legitimation crisis, could ultimately lead to the transformation of management education. This is explored systemically at the institutional, programmatic and pedagogical levels.

Termination of new product development projects was examined as an advocacy process influenced by performance judgments and unobserved performance thresholds, and contextual factors related to the ...

Successful product development requires managing tensions—coping with fluctuating contingencies to foster innovation and efficiency. To investigate this challenge, we explored the nature, dynamics,...

This article argues for the adoption of critical pedagogy by management educators. This change not only recognizes the Profound shifts in competitiveness that have already occurred in the business environment, but would also equip students as independent learners. Students become capable of a complicated understanding of the historical, social, political, and philosophical traditions underlying contemporary conceptions of organizations and management. Truly critical pedagogy necessitates changes in educational roles, curricular content, and classroom practices to create a learning space that supports and encourages students to engage in critical commentary. This space emerges when power in the classroom is de-centered, disciplinary borders become permeable, and issues are problematized. Two examples of implementing critical pedagogy in content (text selection) and process (paradoxical thinking) are presented to illustrate the potential for the transformation of organizational arrangements. Critical pedagogy in management education possesses the capacity for developing students with a greater sensitivity to the emancipatory and transformational possibilities in the future.

Product development is a challenging process, marked by simultaneous demands for innovation and efficiency. While previous research suggests the importance of project management, existing conceptua...

This article explores teaching as an artful endeavor not unlike composing music, painting pictures, choreographing dance, or writing poetry. This art metaphor illustrates the creativity, discipline, and emotional and spiritual energy central to a learning paradigm where the reward for teaching is in the doing. The article focuses on the importance of bringing passion to and deriving meaning from teaching, the emergent nature of the learning journey, and the need to foster student self-sufficiency for life-long learning.

New technologies acquired from outside the firm have become a key ingredient in technology transfer within industrial R&D laboratories and an important source of new product development efforts. This study compares the management and performance of acquired technology projects (n = 24) with product development projects that employed technology originating within the firm's R&D function (n = 57), i.e., in-house projects. Acquired projects differed in a number of ways from in-house projects that were attempting to develop new technologies, but did not differ from in-house projects that were extending existing technologies within the firm. Relationships between project management and project performance also were found to differ across the project types. Similarly, the relationships between management practices and project termination differed across the project types. Overall, acquired technology projects in this study appeared more similar to the extension of technology in-house than to the development of new technology in-house. Factors related to the competitive value and success of acquired technology are discussed.

Although restructuring may represent an appropriate managerial response to global competitive pressures of the 1990s, initial research indicates that reorganizing efforts such as downsizing and re‐engineering are not improving organizational performance. The thesis is that structural approaches to change represent only part of the solution to a complex dilemma. Management also needs to address the role of emotion, and spirituality in particular, in the change process. Develops the concept of spirituality as a kind of positive emotion that serves as a thread connecting the non‐rational dimensions of human behaviour that are so integral to implementing change. The Porras and Silvers (1991) model, which distinguishes organizational transformation from organizational development as intervention strategies, is extended by incorporating the emotional aspects of critical variables into the organizational transformation approach. Variables include vision, transformational leadership, intrinsic motivation depicting work as play, and organizational alignment. Discusses implications for managing spirituality.

Teaching an introductory undergraduate organization theory and design (OT) course can be both challenging and frustrating, due in large part to students' lack of organizational experience as well as to the inherent complexity of the topics. This article describes a pedagogy that draws on dialectical inquiry (thesis-antithesis-synthesis) and involves students actively in classroom learning. Concepts are introduced through dichotomies as typically introduced in OT texts, and discussion elaborates the gray areas between contradictory anchors and relationships among concepts. Finally, addressing case analysis through dialectical debate provides students with an opportunity to better comprehend the often ambiguous and paradoxical nature of managing in contemporary organizations.

Interleukin-15 (IL-15) has a major role in NK-cell homeostasis. Modulation of the relative frequency and expression intensity of the NK-cell receptors by IL-15 may increase NK cell-mediated cytotoxicity in cancer patients. We investigated the receptor repertoire and measured NK-cell activity in newly diagnosed AML patients and evaluated the ex vivo effects of IL-15. The expression of the activating NK cell receptors was significantly decreased in the AML patients compared to that in NK cells of healthy donors. When NK cells obtained from AML patients were cultured with IL-15, expression of the activating receptors was significantly upregulated compared to pre-culture levels. Concomitantly, cytotoxic activity of NK cells against autologous leukemic blasts increased following IL-15 stimulation. This IL-15 induced increase in activity was blocked by neutralizing antibodies specific for the NK cell activating receptors. These pre-clinical data support the future use of IL-15 for NK cell- based therapies for AML patients.

Background Acute myeloid leukemia (AML) in older patients is associated with a poor prognosis, with lower complete remission (CR) rates and worse overall survival compared to younger patients. Moreover, most patients over the age of 70 years do not tolerate standard induction chemotherapy. Alternative therapy with hypomethylating agents can improve CR rates and survival compared to best supportive care, but overall outcomes remain poor with current therapeutic options. Preclinical studies suggest that "epigenetic priming" using decitabine followed by cytarabine increases the cytotoxicity of cytarabine. It is hypothesized that this is due to the reactivation of genes that have been silenced by the malignancy. The aim of this study is to evaluate the efficacy and safety of a novel induction regimen using decitabine followed by cytarabine in older patients with newly diagnosed AML who are not candidates for intensive chemotherapy. Interim response rates were reported at the ASH Annual Meeting in 2014. Here we present updated response rates, treatment-related mortality, and overall survival. Methods This is a phase 2, single arm study at the University of Pittsburgh Cancer Institute (NCT01829503) for patients over the age of 70 years with newly diagnosed AML, or patients over the age of 60 years who are considered not to be candidates for intensive chemotherapy. The induction regimen consisted of decitabine 20mg/m² intravenously (IV) x 5 days followed by cytarabine 100mg/m² continuous IV infusion x 5 days. Patients with no evidence of disease on day 15 bone marrow biopsy proceeded with maintenance decitabine after count recovery; patients otherwise proceeded with a second cycle of induction using the same regimen. Patients with progressive disease after 1 cycle were taken off study. After a second induction cycle, patients who achieved a complete or partial remission proceeded with maintenance decitabine. Maintenance cycles consisted of decitabine 20mg/m² IV x 5 days every 4-8 weeks until disease progression or toxicity. Response rates were determined by the International Working Group Response Criteria in AML. Four-week and 8-week mortality rates were assessed. Results Forty-six subjects were enrolled as of August 2015, 36 of whom were evaluable for response at the time of analysis. Median age was 76 years (range 67-88 years). There were 21 females (45%) and 26 males (55%). The median ECOG performance status was 1. There were 21 patients with poor risk cytogenetics at diagnosis. Of 36 patients who were evaluable for response, 20 patients had a CR and 5 patients had a CRi (CR/CRi rate 69%). Six patients had a partial remission, and 5 patients had resistant disease. All evaluable patients except for 6 received 2 cycles of induction. There were no 4-week mortalities and 4 (8.6%) 8-week mortalities. Deaths were attributed to subdural hemorrhage, multifactorial respiratory failure, progressive AML, and neutropenic sepsis. At a median follow up of 13.5 months, the overall survival is 12.4 months (95% CI:9.7-12.5). Conclusion We have shown that an induction regimen using decitabine as an epigenetic primer followed by cytarabine induces high CR/CRi rates with low treatment-related mortality in older adults with newly diagnosed AML who are not candidates for intensive chemotherapy, a patient population in whom there exists a dire need for novel treatment strategies. In the updated report of this phase 2 study, 69% of patients achieved a CR/CRi, and 4- and 8-week mortality were 0% and 8.6%, respectively. This compares favorably with historical outcomes of both intensive chemotherapy and decitabine monotherapy in older adults in terms of safety and efficacy, respectively. Overall survival was 12.4 months, which also compares favorably to previous reports of survival in this patient population. Methylation analyses at baseline and after decitabine in patients who achieved CR compared to patients who did not respond are ongoing and will be reported. We have demonstrated that decitabine followed by cytarabine is safe and effective in older adults with newly diagnosed AML. Disclosures No relevant conflicts of interest to declare.

Background: Acute myeloid leukemia (AML) in older patients is associated with a poor prognosis, with lower complete remission (CR) rates and worse overall survival compared to younger patients. Moreover, most older patients over the age of 70 years do not tolerate standard induction chemotherapy. Alternative therapy with hypomethylating agents can improve CR rates and survival compared to best supportive care, but overall outcomes remain poor after current therapeutic options in this patient population. Preclinical studies suggest that “epigenetic priming” using decitabine followed by cytarabine increases the cytotoxicity of cytarabine. It is hypothesized that this is due to the reactivation of genes that have been silenced by the malignancy. The aim of this phase II study is to evaluate the efficacy and safety of a novel induction regimen using decitabine followed by cytarabine in older patients with newly diagnosed AML who are not candidates for intensive chemotherapy. Here we present response rates and treatment-related mortality for the first 23 evaluable subjects. Methods: A phase II, single arm study of decitabine and cytarabine is ongoing at the University of Pittsburgh Cancer Institute (NCT 01829503) for patients over the age of 70 years with newly diagnosed AML, or patients over the age of 60 years who are considered not to be candidates for intensive chemotherapy. The induction regimen consists of decitabine 20mg/m² intravenously (IV) x 5 days followed by standard dose cytarabine 100mg/m² continuous IV infusion x 5 days. Patients with no evidence of disease on day 15 bone marrow biopsy proceed with maintenance decitabine. Patients with persistent disease but no evidence of progression proceed with a second cycle of induction using the same regimen. Patients with progressive disease after 1 cycle are taken off study. After a second induction cycle, patients with no evidence of disease, or persistent disease but no evidence of progression, proceed with maintenance decitabine. Maintenance cycles consist of decitabine 20mg/m² IV x 5 days every 4-8 weeks until disease progression. Response rates are evaluated by the International Working Group Response Criteria in AML. Treatment-related mortality is defined at mortality within 8 weeks of initiation of induction therapy. Results: Twenty-five subjects of a planned 37 subjects have been enrolled as of August 2014, 23 of whom were evaluable for response at the time of analysis. At the time of this preliminary analysis, the median age was 76 years (range 68-82 years). There are 11 females (44%) and 14 males (56%). The median ECOG performance status was 1 (range 0-2). There were 14 patients with poor risk cytogenetics at diagnosis. Of the 23 patients who are evaluable for response, there were 14 (61%) patients with a CR and 2 patients with a CRi (CR+CRi rate 70%). Two patients had a partial remission, 1 patient had a morphologic leukemia free state, and 4 patients had resistant disease. All patients except for 2 received 2 cycles of induction. Of the 14 patients who had poor risk cytogenetics at diagnosis, 10 (71%) had a CR, and 8 had normalization of their previous cytogenetic abnormalities. There have been no treatment-related mortalities to date. Conclusion: We have shown that an induction regimen using decitabine as an epigenetic primer followed by cytarabine induces high CR+CRi rates with no treatment-related mortality in older adults with newly diagnosed AML who are not candidates for intensive chemotherapy, a patient population in whom there exists a dire need for novel treatment strategies. In the first report of this phase II study, 70% of patients achieved a CR or CRi, and there were no treatment related mortalities. This compares favorably with historical outcomes of both intensive chemotherapy and decitabine monotherapy in older adults in terms of safety and efficacy, respectively. Final analysis of this clinical trial will include overall survival analysis, rate of grade III and IV adverse events, and epigenetic correlative studies. We have demonstrated that decitabine followed by cytarabine is a safe and effective regimen in older adults with newly diagnosed AML. Disclosures No relevant conflicts of interest to declare.

Interleukin-15 (IL-15) has been demonstrated to play a critical role in the regulation of natural killer (NK) cells. IL-15 induces the differentiation of NK cells from hematopoietic progenitors, stimulates the expansion of peripheral NK cells, and supports their survival. We investigated the role of IL-15 as a homeostatic regulator of NK cells in 29 patients diagnosed with acute myeloid leukemia (AML) and the potential role of IL-15 in enhancing the anti-tumor activity of NK cells in AML patients. The percentage of circulating NK cells was lower (p

An elevated frequency of CD4+CD25high regulatory T cells (Treg) has been reported in the peripheral blood in patients with various solid tumors and hematologic malignancies. Although the increase in Treg seems to be a characteristic feature of most tumors, the functional role of Treg and the mechanisms of suppression, especially in patients with hematologic malignancies, have been less well defined. We investigated Treg-mediated suppression and the responsible mechanisms in thirty newly diagnosed acute myeloid leukemia (AML) patients prior to any treatment and twenty five healthy donors (NC). The percentage of circulating CD4+ CD25high Treg was higher (p

3076 Background: NK cell cytotoxicity is tightly controlled through a balance of signals from the functionally opposing activating and inhibitory receptors found on each cell. Interleukin-15 (IL-15...

Natural killer (NK) cells lyse malignant cells without prior antigen-specific priming and play a critical role in the innate immune response. A balance of signals from activating and inhibiting receptors expressed on each NK cell controls its activity. The growth, differentiation and survival of NK cells have been found to be dependent on interleukin-15 (IL-15). Using multicolor flow cytometry we investigated the receptor repertoire and also measured the NK cell activity in twenty three patients with newly diagnosed acute myeloid leukemia (AML) prior to any treatment. Further, we investigated the ex-vivo effect of IL-15 on the NK cell repertoire and NK cell cytotoxicity. The percentage of circulating NK cells was lower (p Table 1. The effect of IL-15 on the receptor expression in AML patients NK cell Activating Receptors NK cells in AML pts at diagnosis NK cells in AML pts after IL-15 stimulation p value % positive, MFI % positive, MFI NKp30 24, 2.6 84, 6.0 0.001 NKp44 4, 2.4 71, 6.7 0.001 NKp46 32, 2.6 83, 7 0.002 NKG2C 17, 2.2 58, 6.9 0.005 NKG2D 43, 2.5 87, 7.8 0.01

The most effective reinduction regimen for acute myeloid leukemia (AML) patients who do not achieve complete remission (CR) after one cycle of cytarabine combined with an anthracycline is not well established. In an effort to search for new synergistic and non-cross resistant antileukemic regimens different chemotherapeutic combinations have been investigated in refractory AML patients. Multiple regimens including high dose cytarabine, anthracyclines, fludarabine and etoposide have been used with CR rates up to 40%. Mitoxantrone and etoposide have activity in AML as induction agents but their role in reinduction in patients not responding to first line therapy has not been fully established. In the current retrospective study we evaluated the efficacy and toxicity of mitoxantrone and etoposide in AML patients treated at our institution who did not respond to first induction therapy with cytarabine and an anthracycline. A total of fifty seven AML patients were treated with mitoxantrone and etoposide (mean age 55 years, range 18–75 years). Twenty four patients were treated with mitoxantrone 10 mg/m2/d and etoposide 100 mg/m2/d both administered intravenously, days 1 to 5 (regimen 5+5) and thirty three patients were treated with mitoxantrone 10 mg/m2/d administered intravenously days 1 to 3 and etoposide 100 mg/m2/d administered intravenously, days 1 to 5 (regimen 3+5). Twenty six of fifty seven patients (46%) achieved CR. CR was achieved in 38% of patients (9/24) treated with the 5+5 regimen and 52% of patients (17/33) treated with the 3+5 regimen. Mean blast percentage before treatment with mitoxantrone and etoposide was 25% in patients who achieved CR vs 40% in patients who did not achieve CR (p < 0.03). Grade 3/4 hepatic toxicities were seen in 5% (3/57) of patients and there were no grade 3 or 4 renal toxicities. The median duration of neutropenia in patients achieving CR was 29 days after reinduction. 10% (6/57) of the patients died from infectious complications. Cytogenetic analyses were performed prior to first-line therapy in all patients. Patients with favorable cytogenetics treated with etoposide and mitoxantorne had 100% CR (3/3), patients with standard cytogenetics had 58% CR (19/33) and patients with unfavorable cytogenetics had 19% CR (4/21). Overall CR was achieved in 61% (22/36) of patients with favorable and standard cytogenetics. Our data suggest that the combination of etoposide and mitoxantorne is an active and well tolerated regimen, especially in patients with favorable and standard cytogenetics, and warrants further studies in prospective trials.

7054 Background: Regulatory CD4+CD25+ T cells (T reg) are critical regulators of immune tolerance. However, the functional role of T reg in human tumor immunity has been less well studied. The frequency of circulating Treg is increased in patients with solid malignancies. We evaluated the frequency, phenotype and suppressive function of T reg in patients with acute myeloid leukemia (AML). Methods: The frequency and phenotype of CD4+ CD25high T cells were investigated in the peripheral blood of fifteen newly diagnosed AML patients prior to any treatment and fifteen healthy donors by multiparameter flow cytometry. The suppressive function of Treg was evaluated using CFSE-labeled fresh autologous CD4+CD25- T cells activated with an anti-CD3 antibody. Results: The percentage of circulating CD4+ CD25high Treg was higher (p No significant financial relationships to disclose.

Former general practitioner Argyll (b Leigh-on-Sea 1924; q Birmingham 1967), died in Swindon on 1 December 2001. He ran a singlehanded practice in Kinlochleven. He leaves a wife, Ann, and two children.

We review 13 studies dealing with empirical relationships between perceived task scope and employee performance. Results from these studies are contradictory and inconclusive. Most studies use less than adequate measures of employee performance. Moreover, although a causal relationship is assumed, reciprocal or reverse causality may exist. There is a clear need for further theoretical explication and improved laboratory and field research aimed at enhancing both construct validity and substantive considerations.

The article examines the influence of political activity during executive succession on post-succession outcomes. A discussion is presented about the influence of an organization's resource environ...

Using a sample of 222 R&D projects as subunits of the firm, relationships between the dependence of the firm on subunit performance, uncertainty about that performance, and the control of the subun...

Regulatory CD4+CD25+ T cells (T reg) are critical regulators of immune tolerance. Increasing evidence supports the existence of elevated numbers of regulatory T cells in cancer patients. Although the increase of T cells seems to be a characteristic feature in most tumors the functional role of Treg, especially in patients with hematologic malignancies, has been less well defined. Mutlicolor flow cytomerty was used to investigated the frequency and phenotype of CD4+ CD25high T cells in the peripheral blood of thirty seven newly diagnosed acute myeloid leukemia (AML) patients (prior to any treatment) and thirty one healthy donors. The suppressive function of Treg was evaluated using CFSE-labeled fresh autologous CD4+CD25− T cells activated with an anti-CD3 antibody as responders. The percentage of circulating CD4+ CD25high Treg was higher (p < 0.0001) in the AML patients (2.9 ± 0.3%, range 0.1–7%) compared to healthy donors (0.4 ± 0.02%, range 0.1–1%). Percentages of T reg expressing Foxp3, CTLA-4, CD45 RO, Fas ligand (CD95) and GITR were significantly elevated in the circulation of AML patients compared to healthy donors: Foxp3 60vs32% p

Abstract 2678 Poster Board II-654 Natural killer (NK) cell cytotoxicity in patients with acute myeloid leukemia (AML) is significantly decreased relative to that in normal controls (NC). However, the mechanisms responsible for low NK cell activity in AML are not known. We considered the possibility that tumor-cell-derived microvesicles (MV) mediate suppression of NK cells. MV originate from the endosomal compartment of activated normal and neoplastic cells. Evidence suggests that tumor-derived MV exert detrimental effects on cells of the immune system and may play a role in tumor progression. To determine their contribution to immune suppression in AML, MV were isolated from sera of patients newly diagnosed with AML prior to any treatment and used to evaluate MV-mediated NK cell suppression. The protein content of MV isolated using exclusion chromatography and ultracentrifugation from sera of 19 AML patients was significantly higher than that of MV isolated from sera of 25 NC (75μg±12/mL vs 1.2μg±0.4/mL, p Disclosures: No relevant conflicts of interest to declare.

The political economy framework illuminates interplay between the internal and external sociopolitical and economic forces of marketing channels. Framing the collection and analysis of data from retailer informants on channel environments, configuration, and decision structure, a theoretical model is developed for explaining interorganizational responses to uncertainty and dependence constraints of the channel environment. Heterogeneity is hypothesized to precipitate complex and fluid channel structures as a means of coping with uncertainty. In contrast, high levels of variability in the output environment are expected to foster vertical integration and bureaucratization as a means of reducing dependence. Support for both hypotheses is reported and implications for future research are discussed.

The authors wish to thank Stephen Green, Ralph Katerberg, Thomas Keon, George Graen, and the anonymous ASQ reviewers for their helpful comments on earlier versions of this manuscript. To assess the effect of political activity in decision making, the selection of a new dean was studied in 40 professionally oriented colleges at large state universities. Interdependence was found to affect political activity directly, while other aspects of organizational design number of faculty specialists, heterogeneity in faculty training, and the extent of centralization affected political activity indirectly through the development of consensus. Consensus among faculty regarding the attributes to be desired in a new dean had contrary effects on political activity depending on whether interdependence was high or low. When interdependent faculty members were in agreement, less political activity was observed. Agreeing faculty who were not interdependent exhibited more political activity. This interaction suggests that political activity may have two different purposes: to assist existing coalitions to gain advantage or to facilitate the formation of new coalitions. The study extends previous research by measuring political activity and clarifying the process by which it occurs.

Control is defined as the cybernetic regulation of iterative activity within dependence relationships. This framework is used to examine critical aspects of control and its initiation. Two quasi-control responses, dependence reduction and dependence restructuring, are proposed and discussed. Implications of the framework for research and managerial practice are discussed.