Metastatic model of HPV+ oropharyngeal squamous cell carcinoma demonstrates heterogeneity in tumor metastasis

Human papillomavirus induced (HPV+) cancer incidence is rapidly rising, comprising 60–80% of oropharyngeal squamous cell carcinomas (OPSCCs); while rare, recurrent/metastatic disease accounts for nearly all related deaths. An in vivo pre-clinical model for these invasive cancers is necessary for testing new therapies. We characterize an immune competent recurrent/metastatic HPV+ murine model of OPSSC which consists of four lung metastatic (MLM) cell lines isolated from an animal with HPV+ OPSCC that failed cisplatin/radiation treatment. These individual metastatic clonal cell lines were tested to verify their origin (parental transgene expression and define their physiological properties: proliferation, metastatic potential, heterogeneity and sensitivity/resistance to cisplatin and radiation. All MLMs retain expression of parental HPV16 E6 and E7 and degrade P53 yet are heterogeneous from one another and from the parental cell line as defined by Illumina expression microarray. Consistent with this, reverse phase protein array defines differences in protein expression/activation between MLMs as well as the parental line. While in vitro growth rates of MLMs are slower than the parental line, in vivo growth of MLM clones is greatly enhanced. Moreover, in vivo resistance to standard therapies is dramatically increased in 3 of the 4 MLMs. Lymphatic and/or lung metastasis occurs 100% of the time in one MLM line. This recurrent/metastatic model of HPV+ OPSCC retains the characteristics evident in refractory human disease (heterogeneity, resistance to therapy, metastasis in lymph nodes/lungs) thus serving as an ideal translational system to test novel therapeutics. Moreover, this system may provide insights into the molecular mechanisms of metastasis

Examining the Reasons for and Barriers to Becoming a Police Officer

With ever-growing tension between police and the community, both police organizations and communities are recognizing the need and working toward increased representation in police organizations (Brunson, 2007; Szeto, 2014). Despite the effort of many police organizations over the years, the problem of underrepresentation has not improved (Jordan, Fridell, Fagiani, & Kubu, 2009). It has become clear that there is something that has yet to be identified and/or studied preventing underrepresented populations from being interested in or recruited into police organizations. The U.S. Department of Justice and Equal Employment Opportunity Commission’s 2016 report on Advancing Diversity in Law Enforcement identified three factors that may impact the recruitment of those in underrepresented communities into police organizations. These factors include lack of trust in police, the reputation or operational practices of police organizations, and lack of awareness of career opportunities in police organizations. While these factors were identified in the report, there was a lack of research supporting the factors. In an effort to gain a better understanding of what is preventing underrepresented groups from joining law enforcement, participants’ perceptions of trust, culture/policies/practices, and career opportunities in police organizations will be measured. Additionally, motivation to become a police officer and interest in a career as a police officer will be measured to increase the understanding of what does or does not contribute to underrepresented communities being interested in a career as a police officer. Regression analysis will be performed to predict interest in becoming a police officer by using the variables of trust, culture, policies/practices, and career opportunity

Beyond deficiency:Potential benefits of increased intakesof vitamin K for bone and vascular health

Vitamin K is wellknown for its role in the synthesisof a number of blood coagulationfactors.During recent years vitaminK-dependent proteins werediscovered to be of vital importancefor bone and vascular health.Recommendations for dietary vitaminK intake have been made onthe basis of the hepatic requirementsfor the synthesis of bloodcoagulation factors.Accumulatingevidence suggests that the requirementsfor other functions thanblood coagulation may be higher.This paper is the result of a closedworkshop (Paris,November 2002)in which a number of Europeanvitamin K experts reviewed theavailable data and formulated theirstandpoint with respect to recommendeddietary vitamin K intakeand the use of vitamin K-containingsupplements