Wnt signaling is one of the key oncogenic pathways in multiple cancers, and targeting this pathway is an attractive therapeutic approach. However, therapeutic success has been limited because of the lack of therapeutic agents for targets in the Wnt pathway and the lack of a defined patient population that would be sensitive to a Wnt inhibitor. We developed a screen for small molecules that block Wnt secretion. This effort led to the discovery of LGK974, a potent and specific small-molecule Porcupine (PORCN) inhibitor. PORCN is a membrane-bound O-acyltransferase that is required for and dedicated to palmitoylation of Wnt ligands, a necessary step in the processing of Wnt ligand secretion. We show that LGK974 potently inhibits Wnt signaling in vitro and in vivo, including reduction of the Wnt-dependent LRP6 phosphorylation and the expression of Wnt target genes, such as AXIN2.LGK974 is potent and efficacious in multiple tumor models at well-tolerated doses in vivo, including murine and rat mechanistic breast cancer models driven by MMTV-Wnt1 and a human head and neck squamous cell carcinoma model (HN30). We also show that head and neck cancer cell lines with loss-of-function mutations in the Notch signaling pathway have a high response rate to LGK974. Together, these findings provide both a strategy and tools for targeting Wntdriven cancers through the inhibition of PORCN.Wnt inhibition | β-catenin | HNSCC

In fall 2011, the South Carolina Campaign to Prevent Teen Pregnancy (SC Campaign), with funding from Office of Adolescent Health, began replicating an evidence-based curriculum, It's Your Game, Keep It Real in 12 middle schools across South Carolina. Fidelity of the curriculum was monitored by the use of lesson fidelity logs completed by curriculum facilitators and lesson observation logs submitted by independent classroom observers. These data were monitored weekly to identify possible threats to fidelity. The innovative model Fidelity Through Informed Technical Assistance and Training was developed by SC Campaign to react to possible fidelity threats in real time, through a variety of technical assistance modalities. Fidelity Through Informed Technical Assistance and Training guided the 55 hours of technical assistance delivered by the SC Campaign during the first year of It's Your Game, Keep It Real implementation to 18 facilitators across 12 SC middle schools, and achieved 98.4% curriculum adherence and a high quality of implementation scores.

Getting To Outcomes (GTO), an innovative framework for planning, implementing, evaluating, and sustaining interventions has been shown to be effective in helping community-based organizations (CBOs) introduce science-based approaches into their prevention work. However, the Interactive Systems Framework (ISF) suggests that adopting innovations like GTO requires a significant amount of capacity building through training and technical assistance (T/TA). In this study, 11 CBOs and three schools in South Carolina entered into a 3 year program of intense and proactive T/TA based on the ISF to learn how to apply an adaptation of GTO (Promoting Science-Based Approaches-Getting To Outcomes, PSBA-GTO) to their teen pregnancy prevention programs. Using semi-structured interviews, the partnering organizations were assessed at three points in time, pre-T/TA, 12 months, and post T/TA (30 months) for their performance of the steps of GTO in their work. The seven organizations which participated in T/TA until the end of the project received an average of 76 h of TA and 112 h of training per organization. Interview results showed increased performance of all 10 steps of PSBA-GTO by these organizations when conducting their teen pregnancy programs. These results suggest targeted and proactive T/TA can successfully bridge the gap between research and practice by using a three part delivery system, as prescribed in the ISF, which relies on an intermediary prevention support system to ensure accurate and effective translation of research to the everyday work of community-based practitioners.

All youth are at risk for adolescent pregnancy, yet some are more at risk than others. Although risk and protective factors paradigms are certainly not new to the field, this research takes a multilevel ecological approach and seeks to specify the relative merit of individual-level factors compared to social environment factors for explaining sexual behavior. This research explores nuanced similarities and differences between youth who abstain from sex, those who are sexually active and report using contraception, and those who are sexually active and report no contraceptive use. Multivariate and logistic regression approaches highlight aspects of youths' individual characteristics and social environments that may have important influence on their sexual behavior. The regression models showed reliably predicted

Continued efforts are needed to reduce teenage pregnancy in the United States. Implementation of evidence-based curricula in schools is one strategy toward meeting this goal. In 2010, the South Carolina Campaign to Prevent Teen Pregnancy (SC Campaign) received funding to implement a teen pregnancy prevention (TPP) curriculum. Congruent with South Carolina law, the curriculum had to be approved by a school district advisory committee. A case study was conducted to explore factors that led to adoption of the curriculum in one school district. In-depth interviews (n = 17) were conducted with school district staff, advisory committee members, community stakeholders, and SC Campaign staff. An inductive analysis identified several key themes that promoted curriculum adoption: developing networks among TPP advocates, partnerships with local media, establishing a school district commitment to address TPP, assembling a diverse advisory committee, a comprehen-

To examine factors associated with low high-density lipoprotein cholesterol (HDL-C) levels among middle school children. HDL-C levels were the primary outcome of interest. A total of 1,104 middle-school children (mean age 11.6 years, 51.2% female) were included in this analysis, of whom 177 (16%) had an HDL-C level ≤40 mg/dL. More than half of those with low HDL-C were overweight or obese (62.2%) and had greater systolic and diastolic blood pressure, triglyceride (TRG) levels, and low-density lipoprotein cholesterol levels compared with children with an HDL-C level >40 mg/dL. Among those with an HDL-C ≤ 40 mg/dL, 35% also had body mass index ≥85% and TRG levels ≥150 mg/dL. Exercise habits were significantly associated with HDL-C level, whereas sedentary behaviors, such as screen time, were not significantly associated with HDL-C level. Fruit and vegetable intake was also not significantly associated with HDL-C level. Children with low HDL-C levels are more likely to be overweight and to have other physiological indicators of increased cardiovascular risk. Further research is needed to determine if school-based interventions can result in long-term improvements in HDL-C.

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