Moral foundations and HPV vaccine acceptance in the United States: State, parental, and individual factors.

RATIONALE: Appeals to intuitive morality may present a novel approach to addressing vaccine hesitancy. OBJECTIVE: To better understand the relationship between morality and vaccination by employing Moral Foundations Theory to studies surrounding the HPV vaccination at multiple different levels of decision making. METHOD: We employed three different study modalities which examined moralities link to vaccination by employing Moral Foundations Theory. A state-wide ecological study aimed to understand population level trends. Two randomized control interventional studies were then created to understand the effects of Moral Foundations Theory based interventions on both parents of children and individual decision makers. RESULTS: We demonstrated a negative association at the state level between the purity moral foundations and HPV vaccination rates (ß = -.75, SE 0.23; p < .01) and a positive association between loyalty and HPV vaccination rates (ß = 0.62 SE 0.24; p < .05). The parental study built upon this by demonstrating negative association between higher moral purity scores and attitudes towards the HPV vaccine and intention to vaccinate their children (ß = -0.27 SE 0.07; p < .001). Our final study demonstrated a Moral Foundations Theory based intervention was associated with an increase in the odds of indicating an intention to receive the HPV vaccination (adjusted Odds Ratio (aOR) 2.59, 95% Confidence Interval (CI) 1.62-4.14). This equates to a 20% increase in the predicted probability of the intention to receive an HPV vaccine (39% CI (36%-42%) vs 60% CI (57%-63%). CONCLUSIONS: Together, these studies demonstrate that moral foundations, specifically the purity foundation, appear to have a strong and consistent relationship with HPV vaccination. They also demonstrate the how moral values-based interventions may serve as a novel approach to increase HPV vaccine uptake with potential to be employed to target vaccine hesitancy more broadly.

Inhibition of Copper Transport Induces Apoptosis in Triple-Negative Breast Cancer Cells and Suppresses Tumor Angiogenesis.

Treatment of advanced breast cancer remains challenging. Copper and some of the copper-dependent proteins are emerging therapeutic targets because they are essential for cell proliferation and survival, and have been shown to stimulate angiogenesis and metastasis. Here, we show that DCAC50, a recently developed small-molecule inhibitor of the intracellular copper chaperones, ATOX1 and CCS, reduces cell proliferation and elevates oxidative stress, triggering apoptosis in a panel of triple-negative breast cancer (TNBC) cells. Inhibition of ATOX1 activity with DCAC50 disrupts copper homeostasis, leading to increased copper levels, altered spatial copper redistribution, and accumulation of ATP7B to the cellular perinuclear region. The extent and impact of this disruption to copper homeostasis vary across cell lines and correlate with cellular baseline copper and glutathione levels. Ultimately, treatment with DCAC50 attenuates tumor growth and suppresses angiogenesis in a xenograft mouse model, and prevents endothelial cell network formation in vitro Co-treatment with paclitaxel and DCAC50 enhances cytotoxicity in TNBC and results in favorable dose reduction of both drugs. These data demonstrate that inhibition of intracellular copper transport targets tumor cells and the tumor microenvironment, and is a promising approach to treat breast cancer.

Intensive Surveillance with Biannual Dynamic Contrast-Enhanced Magnetic Resonance Imaging Downstages Breast Cancer in BRCA1 Mutation Carriers.

PURPOSE: To establish a cohort of high-risk women undergoing intensive surveillance for breast cancer.Experimental Design: We performed dynamic contrast-enhanced MRI every 6 months in conjunction with annual mammography (MG). Eligible participants had a cumulative lifetime breast cancer risk ≥20% and/or tested positive for a pathogenic mutation in a known breast cancer susceptibility gene. RESULTS: Between 2004 and 2016, we prospectively enrolled 295 women, including 157 mutation carriers (75 BRCA1, 61 BRCA2); participants' mean age at entry was 43.3 years. Seventeen cancers were later diagnosed: 4 ductal carcinoma in situ (DCIS) and 13 early-stage invasive breast cancers. Fifteen cancers occurred in mutation carriers (11 BRCA1, 3 BRCA2, 1 CDH1). Median size of the invasive cancers was 0.61 cm. No patients had lymph node metastasis at time of diagnosis, and no interval invasive cancers occurred. The sensitivity of biannual MRI alone was 88.2% and annual MG plus biannual MRI was 94.1%. The cancer detection rate of biannual MRI alone was 0.7% per 100 screening episodes, which is similar to the cancer detection rate of 0.7% per 100 screening episodes for annual MG plus biannual MRI. The number of recalls and biopsies needed to detect one cancer by biannual MRI were 2.8 and 1.7 in BRCA1 carriers, 12.0 and 8.0 in BRCA2 carriers, and 11.7 and 5.0 in non-BRCA1/2 carriers, respectively. CONCLUSIONS: Biannual MRI performed well for early detection of invasive breast cancer in genomically stratified high-risk women. No benefit was associated with annual MG screening plus biannual MRI screening.See related commentary by Kuhl and Schrading, p. 1693.