Alvin J. Siteman Cancer Center: Cancer prevention perspective

We summarize Siteman Cancer Center catchment that covers 82 counties in southern Illinois and eastern Missouri. We note both the high poverty and cancer rates in many rural counties. Siteman Community Outreach and Engagement has developed a number of strategies to move towards achieving health equity. These include NCI-funded research projects in rural clinics and outreach to improve access to cancer prevention services. To increase capacity for community-engaged research, we have developed and refined a Community Research Fellows Training Program

Microglia modulate hippocampal neural precursor activity in response to exercise and aging

Exercise has been shown to positively augment adult hippocampal neurogenesis; however, the cellular and molecular pathways mediating this effect remain largely unknown. Previous studies have suggested that microglia may have the ability to differentially instruct neurogenesis in the adult brain. Here, we used transgenic Csf1r-GFP mice to investigate whether hippocampal microglia directly influence the activation of neural precursor cells. Our results revealed that an exercise-induced increase in neural precursor cell activity was mediated via endogenous microglia and abolished when these cells were selectively removed from hippocampal cultures. Conversely, microglia from the hippocampi of animals that had exercised were able to activate latent neural precursor cells when added to neurosphere preparations from sedentary mice. We also investigated the role of CX(3)CL1, a chemokine that is known to provide a more neuroprotective microglial phenotype. Intraparenchymal infusion of a blocking antibody against the CX(3)CL1 receptor, CX(3)CR1, but not control IgG, dramatically reduced the neurosphere formation frequency in mice that had exercised. While an increase in soluble CX(3)CL1 was observed following running, reduced levels of this chemokine were found in the aged brain. Lower levels of CX(3)CL1 with advancing age correlated with the natural decline in neural precursor cell activity, a state that could be partially alleviated through removal of microglia. These findings provide the first direct evidence that endogenous microglia can exert a dual and opposing influence on neural precursor cell activity within the hippocampus, and that signaling through the CX(3)CL1-CX(3)CR1 axis critically contributes toward this process

Dissemination and implementation science training needs: Insights from practitioners and researchers

INTRODUCTION: Dissemination and implementation research training has great potential to improve the impact and reach of health-related research; however, research training needs from the end user perspective are unknown. This paper identifies and prioritizes dissemination and implementation research training needs. METHODS: A diverse sample of researchers, practitioners, and policymakers was invited to participate in Concept Mapping in 2014–2015. Phase 1 (Brainstorming) gathered participants' responses to the prompt: To improve the impact of research evidence in practice and policy settings, a skill in which researchers need more training is… The resulting statement list was edited and included subsequent phases. Phase 2 (Sorting) asked participants to sort each statement into conceptual piles. In Phase 3 (Rating), participants rated the difficulty and importance of incorporating each statement into a training curriculum. A multidisciplinary team synthesized and interpreted the results in 2015–2016. RESULTS: During Brainstorming, 60 researchers and 60 practitioners/policymakers contributed 274 unique statements. Twenty-nine researchers and 16 practitioners completed sorting and rating. Nine concept clusters were identified: Communicating Research Findings, Improve Practice Partnerships, Make Research More Relevant, Strengthen Communication Skills, Develop Research Methods and Measures, Consider and Enhance Fit, Build Capacity for Research, and Understand Multilevel Context. Though researchers and practitioners had high agreement about importance (r =0.93) and difficulty (r =0.80), ratings differed for several clusters (e.g., Build Capacity for Research). CONCLUSIONS: Including researcher and practitioner perspectives in competency development for dissemination and implementation research identifies skills and capacities needed to conduct and communicate contextualized, meaningful, and relevant research

Ralph B. Stine and Margaret E. Stine v. Henry Girola and Diane Girola and State Underwriters, Inc. : Petition for Rehearing

In this paper we present a Remote Control Unit (RCU) that can be attached to any location on a rifle, binoculars, etc., and be operated by a single finger of a soldier without removing his hand from the device. Even for a gloved hand a haptic feedback from the RCU will be realized. A RCU prototype, equipped with a single button, is used as a remote Push-to-Talk (PTT) device for the radio being carried by the soldier. The RCU is powered by the radio waves emitted by this radio. The RCU - being attached to the device - works with a receive unit (RXU) that is attached to and operates the radio. The RCU consists of a RF harvester, energy storage device, a button and a transmitter. Laboratory prototypes are demonstrated

Transition to invasive breast cancer is associated with progressive changes in the structure and composition of tumor stroma

Ductal carcinoma in situ (DCIS) is a pre-invasive lesion that is thought to be a precursor to invasive breast cancer (IBC). To understand the changes in the tumor microenvironment (TME) accompanying transition to IBC, we used multiplexed ion beam imaging by time of flight (MIBI-TOF) and a 37-plex antibody staining panel to interrogate 79 clinically annotated surgical resections using machine learning tools for cell segmentation, pixel-based clustering, and object morphometrics. Comparison of normal breast with patient-matched DCIS and IBC revealed coordinated transitions between four TME states that were delineated based on the location and function of myoepithelium, fibroblasts, and immune cells. Surprisingly, myoepithelial disruption was more advanced in DCIS patients that did not develop IBC, suggesting this process could be protective against recurrence. Taken together, this HTAN Breast PreCancer Atlas study offers insight into drivers of IBC relapse and emphasizes the importance of the TME in regulating these processes

Risk prediction models with incomplete data with application to prediction of estrogen receptor-positive breast cancer: prospective data from the Nurses' Health Study

Introduction A number of breast cancer risk prediction models have been developed to provide insight into a woman\u27s individual breast cancer risk. Although circulating levels of estradiol in postmenopausal women predict subsequent breast cancer risk, whether the addition of estradiol levels adds significantly to a model\u27s predictive power has not previously been evaluated. Methods Using linear regression, the authors developed an imputed estradiol score using measured estradiol levels (the outcome) and both case status and risk factor data (for example, body mass index) from a nested case-control study conducted within a large prospective cohort study and used multiple imputation methods to develop an overall risk model including both risk factor data from the main cohort and estradiol levels from the nested case-control study. Results The authors evaluated the addition of imputed estradiol level to the previously published Rosner and Colditz log-incidence model for breast cancer risk prediction within the larger Nurses\u27 Health Study cohort. The follow-up was from 1980 to 2000; during this time, 1,559 invasive estrogen receptor-positive breast cancer cases were confirmed. The addition of imputed estradiol levels significantly improved risk prediction; the age-specific concordance statistic increased from 0.635 ± 0.007 to 0.645 ± 0.007 (P \u3c 0.001) after the addition of imputed estradiol. Conclusion Circulating estradiol levels in postmenopausal women appear to add to other lifestyle factors in predicting a woman\u27s individual risk of breast cancer

Circulating resistin levels and risk of multiple myeloma in three prospective cohorts

BACKGROUND: Resistin is a polypeptide hormone secreted by adipose tissue. A prior hospital-based case-control study reported serum resistin levels to be inversely associated with risk of multiple myeloma (MM). To date, this association has not been investigated prospectively. METHODS: We measured resistin concentrations for pre-diagnosis peripheral blood samples from 178 MM cases and 358 individually matched controls from three cohorts participating in the MM cohort consortium. RESULTS: In overall analyses, higher resistin levels were weakly associated with reduced MM risk. For men, we observed a statistically significant inverse association between resistin levels and MM (odds ratio, 0.44; 95% confidence interval (CI) 0.24-0.83 and 0.54; 95% CI 0.29-0.99, for the third and fourth quartiles, respectively, vs the lowest quartile; Ptrend=0.03). No association was observed for women. CONCLUSIONS: This study provides the first prospective evidence that low circulating resistin levels may be associated with an increased risk of MM, particularly for men