Our model of emergent organizational capacity for compassion proposes that organizations can develop the capacity for compassion without formal direction. Relying on a framework from complexity ...science, we describe how the system conditions of agent diversity, interdependent roles, and social interactions enhance the likelihood of self-organizing around an individual response to a pain trigger. When agents then modify their roles to incorporate compassionate responding, their interactions amplify responses, changing the system, and a new order emerges: organizational capacity for compassion. In this new order the organization's structure, culture, routines, and scanning mechanisms incorporate compassionate responding and can influence future responses to pain triggers.
Proteasome inhibition with bortezomib is a validated approach to the treatment of multiple myeloma, but drug resistance often emerges and limits its utility in the retreatment setting. To begin to ...identify some of the mechanisms involved, we developed bortezomib-resistant myeloma cell lines that, unlike previously reported models, showed no β5 subunit mutations. Instead, up-regulation of the insulin-like growth factor (IGF)–1 axis was identified, with increased autocrine and paracrine secretion of IGF-1, leading to increased activation of the IGF-1 receptor (IGF-1R). Exogenous IGF-1 reduced cellular sensitivity to bortezomib, whereas pharmacologic or small hairpin RNA–mediated IGF-1R suppression enhanced bortezomib sensitivity in cell lines and patient samples. In vitro studies with OSI-906, a clinically relevant dual IGF-1R and insulin receptor inhibitor, showed it acted synergistically with bortezomib, and potently resensitized bortezomib-resistant cell lines and patient samples to bor-tezomib. Importantly, OSI-906 in combination with bortezomib also overcame bor-tezomib resistance in an in vivo model of myeloma. Taken together, these data support the hypothesis that signaling through the IGF-1/IGF-1R axis contributes to acquired bortezomib resistance, and provide a rationale for combining bortezomib with IGF-1R inhibitors like OSI-906 to overcome or possibly prevent the emergence of bortezomib-refractory disease in the clinic.
Attitudes about corporate social responsibility Kolodinsky, Robert W; Madden, Timothy M; Zisk, Daniel S ...
Journal of business ethics,
2010, 20100101, 1-2010, 2010-1-00, Letnik:
91, Številka:
2
Journal Article
Recenzirano
Four predictors were posited to affect business student attitudes about the social responsibilities of business, also known as corporate social responsibility (CSR). Applying Forsyth's (1980, ..."Journal of Personality and Social Psychology" 39, 175–184, 1992, "Journal of Business Ethics" 11, 461–470) personal moral philosophy model, we found that ethical idealism had a positive relationship with CSR attitudes, and ethical relativism a negative relationship. We also found materialism to be negatively related to CSR attitudes. Spirituality among business students did not significantly predict CSR attitudes. Understanding the relationship between CSR attitudes and the significant predictors has important implications for researchers and teachers in particular.
Long-term unemployed workers are individuals who have been unemployed continuously for six or more months. Evidence shows that this form of unemployment is particularly deleterious, necessitating ...inquiry into factors that influence the duration of unemployment for these workers and their readjustment to work. Embeddedness theory sheds new light on this problem by predicting that community attachments exert a powerful influence on the choices and mobility of employees, raising the possibility that the attachments functionally embedding employees in jobs also may limit the choices and mobility of unemployed workers. However, upon re-employment, the theory also predicts that community embeddedness would facilitate positive work attitudes and attachments, thus becoming functional for re-employed workers. Accordingly, our focal purpose in this paper is to explore how community embeddedness impacts workers during long-term unemployment and upon re-employment. Incorporating a sample of long-term unemployed workers over two time periods, we find that unemployment duration extends as community embeddedness and worker age increase and that community embeddedness affects job embeddedness, job satisfaction, and turnover intentions upon re-employment as a function of job search effort.
•Among long-term unemployed individuals, unemployment duration increases with age and community embeddedness.•Job search motivation of workers affected re-employment success in Time 2.•Community embeddedness during unemployment affected work attitudes and attachments upon re-employment.•Job search effort during unemployment moderates these relationships.•The experience of job search during long-term unemployment affects re-employment adjustments of workers.
Optically pumped molecular gas amplifiers having a gain medium contained in a hollow-core optical fiber are investigated with numerical modeling to understand the primary physical processes that ...affect amplifier output and efficiency. A comparison of computational results with experimental measurements of incident pump, absorbed pump, and emitted mid-IR from a pulsed, acetylene-filled, hollow-core fiber amplifier Opt. Exp.25, 13351 (2017) is used to explore the effects of various physical processes on pulsed amplifier operation. Single frequency, one-dimensional, time-dependent models are shown to align with experimentally measured lasing thresholds and ratios of absorbed pump to emitted laser energy but significantly over predict the amount of incident pump energy that is absorbed. A two-dimensional, time-dependent model that assumes Gaussian spectral and radial intensity profiles for the pump is developed and shows an improved ability to capture pump absorption. Results indicate that 1D, time-dependent models have utility in guiding experiments but the significant influence of the pump and laser propagation modes and the pump spectral characteristics on efficiency, threshold, and signal output must be explicitly included in high-fidelity high-power modeling.
In good company Madden, Laura; Mathias, Blake D.; Madden, Timothy M.
Management research review,
01/2015, Letnik:
38, Številka:
3
Journal Article
Recenzirano
Purpose – This paper aims to explore the relationships among perceived organizational support, positive relationships at work and intent to turnover through a social exchange theory lens. The main ...contribution of this paper is the investigation of different types of positive workplace relationships on employee withdrawal behaviors. Design/methodology/approach – A 49-item survey was developed through a review of literature related to positive workplace relationships and intent to turnover. Surveys were made available to 200 healthcare employees; 73 surveys were accurately completed and used to test a mediated model of positive relationships at work. Findings – Positive relationships at work were found to have a mediating effect between perceived organizational support and intent to turnover. Additionally, perceived organizational support was found to have direct and indirect effects on intent to turnover. Practical implications – Managers can affect employees’ intentions to turnover by improving practices that provide support to employees and encouraging positive relationships with coworkers. Additional literature related to our variables of interest suggests that employees perceive more support when their organizations offer commensurate rewards, opportunities for growth and participation in decision making. Originality/value – This study speaks to those researchers and managers interested in employees’ motivations for staying in or leaving from their organizations. Turnover and related withdrawal behaviors are expensive for organizations, so discovering the factors that members value offers organizations the ability to affect their members’ intentions to turnover. Additionally, the exploration of relationships between perceived organizational support and positive relationships at work suggests that different support mechanisms play different roles in affecting organizational and individual outcomes.
Overcoming the profound immunosuppression in patients with solid cancers has impeded efficacious immunotherapy. Signal transducers and activators of transcription 3 (STAT3) has recently emerged as a ...potential target for effective immunotherapy, and in this study, we describe a novel small molecule inhibitor of STAT3 that can penetrate the central nervous system (CNS) in mice and in physiologically relevant doses in vitro and reverse tolerance in immune cells isolated from glioblastoma multiforme (GBM) patients. Specifically, it induces the expression of costimulatory molecules on peripheral macrophages and tumor-infiltrating microglia, stimulates the production of the immune-stimulatory cytokines interleukin 2 (IL-2), IL-4, IL-12, and IL-15, and induces proliferation of effector T cells from GBM patients that are refractory to CD3 stimulation. We show that the functional enhancement of immune responses after STAT3 inhibition is accompanied by up-regulation of several key intracellular signaling molecules that critically regulate T-cell and monocyte activation. Specifically, the phosphorylation of Syk (Tyr352) in monocytes and ZAP-70 (Tyr319) in T cells are enhanced by the STAT-3 inhibitor in marked contrast to toll-like receptor and T-cell receptor agonists, respectively. This novel small molecule STAT3 inhibitor has tremendous potential for clinical applications with its penetration into the CNS, easy parental administration, direct tumor cytotoxicity, and potent immune adjuvant responses in immunosuppressed cancer patients.
Study abroad programs (SAPs) are desirable experiential learning opportunities that can enrich students and faculty alike. Faculty participate in SAPs because their immersive learning contexts offer ...a variety of personal and professional benefits, including the chance to meet new research contacts, tour cultural sites, and get to know students in a more informal context. Despite these benefits, SAPs contain a substantial shadow side for faculty and involve unanticipated temporal, financial, and physiological costs. Additionally, risks—some of which can never be fully avoided—also remain sources of stress and anxiety. This study uses a qualitative approach to identify and shed light on these understated issues that are typically relegated to the shadow. Questionnaires and semistructured interviews with experienced SAP faculty leaders provide evidence for these elements, which is the first step in aligning faculty expectations with the likely realities that await them abroad. The study concludes with practices and strategies to mitigate some of the costs and risks that faculty may face before, during, and after their involvement in an SAP.
To determine the dose-limiting toxicity and maximum-tolerated dose of the proteasome inhibitor bortezomib administered intravenously weekly for 4 every 5 weeks; to determine the bortezomib ...pharmacokinetics and pharmacodynamics using plasma levels and an assay for 20S proteasome inhibition (PI) in whole blood; to correlate toxicity with bortezomib dose and degree of 20S PI; and to conduct a preliminary determination of the antitumor activity of bortezomib in patients with androgen independent prostate cancer (AIPCa).
Fifty-three patients (48 with AIPCa) received 128 cycles of bortezomib in doses ranging from 0.13 to 2.0 mg/m(2)/dose, utilizing a careful escalation scheme with a continuous reassessment method. Pharmacokinetic and pharmacodynamic studies were performed in 24 patients (at 1.45 to 2.0 mg/m(2)).
A dose-related 20S PI was seen, with dose-limiting toxicity at 2.0 mg/m(2) (diarrhea, hypotension) occurring at an average 1-hour post-dose of >/= 75% 20S PI. Other side effects were fatigue, hypertension, constipation, nausea, and vomiting. No relationship was seen between body-surface area and bortezomib clearance over the narrow dose range tested. There was evidence of biologic activity (decline in serum prostate-specific antigen and interleukin-6 levels) at >/= 50% 20S PI. Two patients with AIPCa had prostate-specific antigen response and two patients had partial response in lymph nodes.
The maximum-tolerated dose and recommended phase II dose of bortezomib in this schedule is 1.6 mg/m(2). Biologic activity (inhibition of nuclear factor-kappa B-related markers) and antitumor activity is seen in AIPCa at tolerated doses of bortezomib. This agent should be further explored with chemotherapy agents in advanced prostate cancer.
PDF
