In an attempt to reap the purported benefits that "knowledge workers" bring to organizations, many police departments have shifted to a community problem-oriented policing philosophy. Rather than focusing on enforcement and incarceration, this philosophy is based on the dissemination of information to promote a proactive, preventative approach to reduce crime and disorder. In keeping with much of the contemporary literature on the "learning organization" (sometimes called the "knowledge organization"), police departments hope to deter crime through the knowledge benefits that derive from information and its associated technologies. With goals to stimulate productivity, performance, and effectiveness, police departments across the country are employing information technology to turn police officers into problem solvers and to leverage their intellectual capital to preempt crime and neighborhood deterioration.Many public and private organizations are striving to change their operations toward this same concept of the knowledge worker. Information technology is often touted as a vehicle for capturing, tracking, sorting, and providing information to advance knowledge, thus leading to improvements in service-delivery efforts. Based on an extensive study of police departments that have attempted to implement a knowledge-worker paradigm (supported by information technology initiatives), this research explores the feasibility, effectiveness, and limitations of information and technology in promoting the learning organization in the public sector.Mary Maureen Brown is an associate professor of public administration in the School of Government at the University of North Carolina at Chapel Hill where she serves as the codirector of the Center for Public Technology. Her teaching and research interests concentrate on the use of information based technologies for reengineering operations to improve service delivery throughout all levels of government. Her service activities focus on the design, development, and implementation of advanced technologies to enhance organizational operations.Great attention has been given to the explosion of information technology that occurred during the last two decades of the twentieth century. In that short period, annual expenditures for information and technology grew to $600 billion in the United States and $2 trillion globally (G2 Research 1998; WITSA 1998-not found in references). With the information revolution came the resurrection of an age-old debate regarding the role of information in organizational decision making. The debate centers on how administrators employ information in decision making and problem solving. Some authorities advocate the use of information as a "signaling component" for feeding the decision process. In this approach, information is employed as a stabilizing or adaptive mechanism to gain leverage or control over a turbulent environment. These scholars assume a normative view of the "rational man." Others counter that information often is employed in a

IntroductionGene amplification of CCND1 is observed in a subgroup of breast cancers with poor prognosis, whereas overexpression of the protein cyclin D1 has been linked to both worse and better clinical outcome. CCND1 amplification and protein overexpression have also been associated with resistance to treatment with tamoxifen or even to a potentially detrimental effect of tamoxifen.MethodsTo clarify these challenging and partly contrasting treatment predictive and prognostic links for cyclin D1 we analysed a large cohort of postmenopausal breast cancer patients randomised to receive either adjuvant anastrozole or tamoxifen, as part of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial. The CCND1 amplification status and protein expression of cyclin D1 were assessed by chromogenic in situ hybridisation and immunohistochemistry, respectively, in 1,155 postmenopausal, oestrogen-receptor-positive breast cancer patients included in the TransATAC substudy.ResultsAmplification of CCND1 was observed in 8.7% of the tumours and was associated with increased risk of disease recurrence (hazard ratio = 1.61; 95% confidence interval, 1.08 to 2.41) after adjustment for other clinicopathological parameters. In contrast, nuclear expression of cyclin D1 protein was associated with decreased recurrence rate (hazard ratio = 0.6; 95% confidence interval, 0.39 to 0.92). The intensity of nuclear or cytoplasmic expression was not of prognostic value. There was no significant interaction between cyclin D1 status and treatment efficacy, ruling out any major detrimental effect of tamoxifen in CCND1-amplified postmenopausal breast cancer.ConclusionsIn summary, CCND1 amplification and low nuclear expression of cyclin D1 predicted poor clinical outcome in postmenopausal breast cancer patients treated with either anastrozole or tamoxifen.Trial RegistrationCurrent Controlled Trials ISRCTN18233230.

Background Aberrant activation of Axl is implicated in the progression of hepatocellular carcinoma (HCC). We explored the biologic significance and preclinical efficacy of Axl inhibition as a therapeutic strategy in sorafenib-naive and resistant HCC. Methods We evaluated Axl expression in sorafenib-naive and resistant (SR) clones of epithelial (HuH7) and mesenchymal origin (SKHep-1) using antibody arrays and confirmed tissue expression. We tested the effect of Axl inhibition with RNA-interference and pharmacologically with R428 on a number of phenotypic assays. Results Axl mRNA overexpression in cell lines ( n = 28) and RNA-seq tissue datasets ( n = 373) correlated with epithelial-to-mesenchymal transition (EMT). Axl was overexpressed in HCC compared to cirrhosis and normal liver. We confirmed sorafenib resistance to be associated with EMT and enhanced motility in both HuH7-SR and SKHep-1-SR cells documenting a 4-fold increase in Axl phosphorylation as an adaptive feature of chronic sorafenib treatment in SKHep-1-SR cells. Axl inhibition reduced motility and enhanced sensitivity to sorafenib in SKHep-1SR cells. In patients treated with sorafenib ( n = 40), circulating Axl levels correlated with shorter survival. Conclusions Suppression of Axl-dependent signalling influences the transformed phenotype in HCC cells and contributes to adaptive resistance to sorafenib, providing a pre-clinical rationale for the development of Axl inhibitors as a measure to overcome sorafenib resistance.

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The interaction between Axl receptor tyrosine kinase and its main ligand Gas6 has been implicated in the progression of a wide number of malignancies. More recently, overexpression of Axl has emerged as a key molecular determinant underlying the development of acquired resistance to targeted anticancer agents. The activation of Axl is overexpression-dependent and controls a number of hallmarks of cancer progression including proliferation, migration, resistance to apoptosis and survival through a complex network of intracellular second messengers. Axl has been noted to influence clinically meaningful end points including metastatic recurrence and survival in the vast majority of tumour types. With Axl inhibitors having gained momentum as novel anticancer therapies, we provide an overview of the biological and clinical relevance of this molecular pathway, outlining the main directions of research.

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PURPOSE: Significant gaps in care and limited existing models establish the need to innovate systems of care for youth with special health care needs in the transition between pediatric to adult health care settings. METHODS: Using implementation science, a statewide transition support program was created. University and community partners explored needs and adopted a strategic plan and funding sources. The existing consensus statement provided a framework. A team was hired, policies were piloted and the initial ambulatory consultative transition service for youth with special needs ages 11 to 22 was launched. Full program activities during year four were analyzed. RESULTS: During 2011, there were 139 consultations for youth with intellectual disability and/or physical disability (average 16.74 years, 46% female). Services include routine and focused co-morbidity screening and recommendations, care coordination of complex health and community service needs, and support for families. The evolving transdisciplinary team adapted their methods to collaborate with a growing population of youth and primary care providers. CONCLUSION: A statewide transition support program is a viable delivery model to provide needed resources for youth, families and primary care practices. Weekly improvement meetings continue to adapt services to sustain family satisfaction and community provider satisfaction.