Clohisy, Denis R.

Abstract: The current workforce in the United States is rapidly changing and is increasingly inclusive of individuals from a broad range of ages, ethnicities, and cultural backgrounds. Engaging and leading a diverse workforce creates great opportunities for innovation and adaptation in our evolving medical economic and clinical care delivery environment. For optimal engagement of employees and partners, orthopaedic surgeons must develop the necessary skills for executing change inside complex organizations and across teams composed of a variety of providers and skilled workers. Important skills include leadership, effective communication, and negotiation within an ever-changing employee milieu. Understanding generalizable differences between age-based generations can increase the effectiveness of one’s strategies to execute change and increase organizational performance. One of the greatest impediments to effective communication and negotiations that all leaders face is unconscious bias. For leaders, even the tiniest unconscious biases have an outsized impact. Common domains that harbor unconscious bias include sex, race, and ethnicity. Addressing unconscious bias begins with developing awareness and then deploying various tactics that might include equity in compensation, promotion, and “being heard.” Effective negotiation skills also are essential to lead a diverse workforce and develop a successful organization. The most basic goal in any negotiation should be to establish a relationship (or deepen an existing relationship) while seeking an agreement that provides win-win opportunities for all parties. To effectively achieve a win-win scenario, leaders must recognize and address their tendency to interpret others’ behaviors, values, and beliefs through the lens of their own beliefs and experiences. Finally, and fortunately, there is a set of leader attributes that transcends the generational differences and diversity that is encountered in the workplace. These attributes include integrity, credibility, effective listening, having a vision of your destination, fairness, humility, and caring.

Abstract 2-Methoxyestradiol (2ME2), a physiologic metabolite of 17β-estradiol (estrogen), has emerged as a promising cancer therapy because of its potent growth-inhibitory and proapoptotic effects on both endothelial and tumor cells. 2ME2 also suppresses osteoclast differentiation and induces apoptosis of mature osteoclasts, and has been shown to effectively repress bone loss in an animal model of postmenopausal osteoporosis. Given these observations, we have examined whether 2ME2 could effectively target metastasis to bone, osteolytic tumors, and soft tissue tumors. A 4T1 murine metastatic breast cancer cell line was generated that stably expressed Far Red fluorescence protein (4T1/Red) to visualize tumor development and metastasis to bone. In an intervention study, 4T1/Red cells were injected into bone marrow of the left femur and the mammary pad. In the latter study, 2ME2 (10, 25, and 50 mg/kg/d) treatment began on the same day as surgery and was continued for the 16-day duration of study. Tumor cell growth and metastasis to bone were monitored and bone volume was determined by micro-computed tomography. 2ME2 inhibited tumor growth in soft tissue, metastasis to bone, osteolysis, and tumor growth in bone, with maximum effects at 50 mg/kg/d. Furthermore, tumor-induced osteolysis was significantly reduced in mice receiving 2ME2. In vitro, 2ME2 repressed osteoclast number by inducing apoptosis of osteoclast precursors as well as mature osteoclasts. Our data support the conclusion that 2ME2 could be an important new therapy in the arsenal to fight metastatic breast cancer. [Cancer Res 2007;67(21):10106–11]