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An intronic GGGGCC repeat expansion inC9orf72is a common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. The repeats are transcribed in both sense and antisense directions to generate distinct dipeptide repeat proteins, of which poly(GA), poly(GR) and poly(PR) have been implicated in contributing to neurodegeneration. Poly(PR) binding to RNA may contribute to toxicity, but analysis of poly(PR)-RNA binding on a genome-wide scale has not yet been carried out. We therefore performed crosslinking and immunoprecipitation (CLIP) analysis in human cells to identify the RNA binding sites of poly(PR). We found that poly(PR) binds to nearly 600 RNAs, with the sequence GAAGA enriched at the binding sites.In vitroexperiments showed that polyGAAGA RNA binds poly(PR) with higher affinity than control RNA and induces phase-separation of poly(PR) into condensates. These data indicate that poly(PR) preferentially binds to polyGAAGA-containing RNAs, which may have physiological consequences.

A GGGGCC repeat expansion in theWe used the single molecule array (Simoa) platform to develop an immunoassay for measuring poly(GP) dipeptide repeat proteins (DPRs) generated by theWe show the assay to be highly sensitive and robust, passing extensive qualification criteria including low intraplate and interplate variability, a high precision and accuracy in measuring both calibrators and samples, dilutional parallelism, tolerance to sample and standard freeze-thaw and no haemoglobin interference. We used this assay to measure poly(GP) in CSF samples collected through the Genetic FTD Initiative (N=40

A GGGGCC repeat expansion in the C9orf72 gene is the most common cause of genetic frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). As potential therapies targeting the repeat expansion are now entering clinical trials, sensitive biomarker assays of target engagement are urgently required. We utilised the single molecule array (Simoa) platform to develop an immunoassay for measuring poly(GP) dipeptide repeat proteins (DPRs) generated by the repeat expansion in CSF of people with C9orf72-associated FTD/ALS. We show the assay to be highly sensitive and robust, passing extensive qualification criteria including low intra- and inter-plate variability, a high precision and accuracy in measuring both calibrators and samples, dilutional parallelism, tolerance to sample and standard freeze-thaw and no haemoglobin interference. We used this assay to measure poly(GP) DPRs in the CSF of samples collected through the Genetic FTD Initiative. We found it had 100% specificity and 100% sensitivity and a large window for detecting target engagement, as the C9orf72 CSF sample with the lowest poly(GP) signal had 8-fold higher signal than controls and on average values from C9orf72 samples were 38-fold higher than controls, which all fell below the lower limit of quantification of the assay. These data indicate that a Simoa-based poly(GP) DPR assay is suitable for use in clinical trials to determine target engagement of therapeutics aimed at reducing C9orf72 repeat-containing transcripts.

Intronic GGGGCC (G4C2) hexanucleotide repeat expansion within the human C9orf72 gene represents the most common cause of familial forms of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9ALS/FTD). Repeat‐associated non‐AUG (RAN) translation of repeat‐containing C9orf72 RNA results in the production of neurotoxic dipeptide‐repeat proteins (DPRs). Here, we developed a high‐throughput drug screen for the identification of positive and negative modulators of DPR levels. We found that HSP90 inhibitor geldanamycin and aldosterone antagonist spironolactone reduced DPR levels by promoting protein degradation via the proteasome and autophagy pathways respectively. Surprisingly, cAMP‐elevating compounds boosting protein kinase A (PKA) activity increased DPR levels. Inhibition of PKA activity, by both pharmacological and genetic approaches, reduced DPR levels in cells and rescued pathological phenotypes in a Drosophila model of C9ALS/FTD. Moreover, knockdown of PKA‐catalytic subunits correlated with reduced translation efficiency of DPRs, while the PKA inhibitor H89 reduced endogenous DPR levels in C9ALS/FTD patient‐derived iPSC motor neurons. Together, our results suggest new and druggable pathways modulating DPR levels in C9ALS/FTD., Screening small‐molecule agonists for the ability to modulate accumulation of toxic polypeptides suggests PKA signaling, proteasomal and autophagy pathways as potential therapeutic targets for C9orf72‐associated ALS/FTD.

A GGGGCC hexanucleotide repeat expansion within the C9orf72 gene is the most common genetic cause of both amyotrophic lateral sclerosis and frontotemporal dementia. Sense and antisense repeat-containing transcripts undergo repeat-associated non-AUG-initiated translation to produce five dipeptide proteins (DPRs). The polyGR and polyPR DPRs are extremely toxic when expressed in Drosophila neurons. To determine the mechanism that mediates this toxicity, we purified DPRs from the Drosophila brain and used mass spectrometry to identify the in vivo neuronal DPR interactome. PolyGR and polyPR interact with ribosomal proteins, and inhibit translation in both human iPSC-derived motor neurons, and adult Drosophila neurons. We next performed a screen of 81 translation-associated proteins in GGGGCC repeat-expressing Drosophila to determine whether this translational repression can be overcome and if this impacts neurodegeneration. Expression of the translation initiation factor eIF1A uniquely rescued DPR-induced toxicity in vivo, indicating that restoring translation is a potential therapeutic strategy. These data directly implicate translational repression in C9orf72 repeat-induced neurodegeneration and identify eIF1A as a novel modifier of C9orf72 repeat toxicity. Electronic supplementary material The online version of this article (10.1007/s00401-018-1946-4) contains supplementary material, which is available to authorized users.

A surge in the accumulation of oxidants generates shifts in the cellular redox potential during early stages of plant infection with pathogens and activation of effector-triggered immunity (ETI). The redoxome, defined as the proteome-wide oxidative modifications of proteins caused by oxidants, has a well-known impact on stress responses in metazoans. However, the identity of proteins and the residues sensitive to oxidation during the plant immune response remain largely unknown. Previous studies of the thimet oligopeptidases TOP1 and TOP2 placed them in the salicylic acid dependent branch of ETI, with a current model wherein TOPs sustain interconnected organellar and cytosolic pathways that modulate the oxidative burst and development of cell death. Herein, we characterized the ETI redoxomes in Arabidopsis (Arabidopsis thaliana) wild-type Col-0 and top1top2 mutant plants using a differential alkylation-based enrichment technique coupled with label-free mass spectrometry-based quantification. We identified cysteines sensitive to oxidation in a wide range of protein families at multiple time points after pathogen infection. Differences were detected between Col-0 and top1top2 redoxomes regarding the identity and number of oxidized cysteines, and the amplitude of time-dependent fluctuations in protein oxidation. Our results support a determining role for TOPs in maintaining the proper level and dynamics of proteome oxidation during ETI. This study significantly expands the repertoire of oxidation-sensitive plant proteins and can guide future mechanistic studies.

Hexanucleotide GGGGCC repeat expansion in C9ORF72 is the most prevalent genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). One pathogenic mechanism is the aberrant accumulation of dipeptide repeat (DPR) proteins produced by the unconventional translation of expanded RNA repeats. Here, we performed genome-wide CRISPR-Cas9 screens for modifiers of DPR protein production in human cells. We identified DDX3X, an RNA helicase, suppresses the repeat-associated non-AUG translation of GGGGCC repeats. DDX3X directly binds to (GGGGCC)n RNAs, but not antisense (CCCCGG)n RNAs. Its helicase activity is essential for the translation repression. Reduction of DDX3X increases DPR levels in C9ORF72-ALS/FTD patient cells and enhances (GGGGCC)n-mediated toxicity in Drosophila. Elevating DDX3X expression is sufficient to decrease DPR levels, rescue nucleocytoplasmic transport abnormalities, and improve survival of patient iPSC-differentiated neurons. This work identifies genetic modifiers of DPR protein production and provides potential therapeutic targets for C9ORF72-ALS/FTD.

Colorectal cancer (CRC) is the second and third leading cause of cancer death for Hispanic men and women, respectively. CRC can be prevented if precursors are detected early and removed and can be successfully treated if discovered early. While one-on-one interventions for increasing CRC screening (CRCS) are recommended, few studies specifically assess the effectiveness of lay health worker (LHW) approaches using different educational materials.To develop and evaluate the effectiveness of two LHW-delivered CRCS interventions known as Vale la Pena (VLP; "It's Worth It!") on increasing CRCS among Hispanics.The study design was a cluster randomized controlled trial with two treatment arms.Six hundred and sixty five Hispanics 50 years and older were recruited from 24 colonias (neighborhoods) in the Lower Rio Grande Valley of the Texas-Mexico border.The interventions were a small media print intervention (SMPI) (including DVD and flipchart), and a tailored interactive multimedia intervention (TIMI) delivered on tablet computers. A no intervention group served as the comparison group. Data were collected between 2007 and 2009 and analyzed between 2009 and 2013.Measures assessed CRCS behavior, self-efficacy, knowledge, and other psychosocial constructs related to CRCS and targeted through VLP.Among participants reached for follow-up, 18.9 % in the SMPI group, 13.3 % in the TIMI group, and 11.9 % in the comparison group completed CRCS. Intent-to-treat analysis showed that 13.6 % in the SMPI group, 10.2 % in the TIMI group, and 10.8 % in the comparison group completed CRCS. These differences were not statistically significant.Results indicated that there are no significant differences in CRCS uptake between groups.

Glycans are inherently heterogeneous, yet glycosylation is essential in eukaryotes, and glycans show characteristic cell type-dependent distributions. By using an immortalized human mesenchymal stromal cell (MSC) line model, we show that both N- and O-glycan processing in the Golgi functionally modulates early steps of osteogenic differentiation. We found that inhibiting O-glycan processing in the Golgi prior to the start of osteogenesis inhibited the mineralization capacity of the formed osteoblasts 3 weeks later. In contrast, inhibition of N-glycan processing in MSCs altered differentiation to enhance the mineralization capacity of the osteoblasts. The effect of N-glycans on MSC differentiation was mediated by the phosphoinositide-3-kinase (PI3K)/Akt pathway owing to reduced Akt phosphorylation. Interestingly, by inhibiting PI3K during the first 2 days of osteogenesis, we were able to phenocopy the effect of inhibiting N-glycan processing. Thus, glycan processing provides another layer of regulation that can modulate the functional outcome of differentiation. Glycan processing can thereby offer a novel set of targets for many therapeutically attractive processes., Summary: Both N- and O-glycan processing modulate MSC differentiation early during osteogenesis to influence mineral formation. Inhibition of N-glycan processing increases mineralization.

Background Hispanic women have a higher incidence of cervical cancer than all other races and ethnicities. In Hispanic subgroups, Mexican American women were among the least likely to have received cervical cancer screening. In a recent RCT, Ayudando a las Mujeres con Informacion, Guia, y Amor para su Salud (AMIGAS) was shown to increase cervical cancer screening rates among women of Mexican descent at 6 months in all intervention arms compared to the control arm. Limited information exists about the economics of interventions to increase cervical cancer screening rates among women of Mexican descent. Purpose This study aims to estimate the cost-effectiveness of the alternative AMIGAS intervention methods for increasing cervical cancer screening among low-income women of Mexican descent in three U.S. communities. Methods Cost data were collected from 2008 to 2011 alongside the AMIGAS study of 613 women. Receipt of Pap test within 6 months of intervention was the primary outcome measure in the cost-effectiveness analysis, conducted during 2012−2013. Results The cost per additional woman screened comparing the video-only intervention to usual care was $980. The cost increased to $1,309 with participant time cost included. With an additional cost per participant of $3.90 compared to flipchart only, the full AMIGAS program (video plus flipchart) yielded 6.8% additional women screened. Conclusions Results on the average and incremental cost-effectiveness of the AMIGAS program elements may assist health policymakers and program managers to select and appropriately budget for interventions shown to increase cervical cancer screening among low-income women of Mexican descent.

BACKGROUND: Considerable efforts have been undertaken in the United States to reduce cervical cancer incidence and mortality by increasing screening; however, disparities in screening rates continue to exist among certain racial and ethnic minority groups. The objective of the current study was to determine the effectiveness of a lay health worker-delivered intervention—AMIGAS (Ayudando a las Mujeres con Informacion, Guia, y Amor para su Salud [helping women with information, guidance, and love for their health])—to increase Papanicolaou (Pap) test screening among 3 populations of women of Mexican origin. METHODS: Six hundred thirteen women of Mexican origin in 3 treatment sites were randomized among 4 study arms: the full AMIGAS program with a video and a flip chart (n = 151), the AMIGAS program without the video (n = 154), the AMIGAS program without the flip chart (n = 155), and a usual care control group (n = 153). Six months after enrollment, women were surveyed and reported whether or not they had been screened. RESULTS: Women in any of the intervention arms were statistically significantly more likely to report being screened than those in the usual care group in both an intent-to-treat analysis and a per-protocol analysis. In the intent-to-treat analysis, 25% of women in the control group and 52% in the full AMIGAS program group reported having had Pap tests (P < .001); in the per-protocol analysis, the percentages were 29% and 62%, respectively (P < .001). CONCLUSIONS: AMIGAS was effective in increasing Pap test screening among women of Mexican descent when used in a 1-to-1 setting. Future research should compare the 1-on-1 intervention with the group-based intervention. Cancer 2013. © 2012 American Cancer Society.

Context Screening reduces mortality from breast, cervical, and colorectal cancers. The Guide to Community Preventive Services previously conducted systematic reviews on the effectiveness of 11 interventions to increase screening for these cancers. This article presents results of updated systematic reviews for nine of these interventions. Evidence acquisition Five databases were searched for studies published during January 2004-October 2008. Studies had to (1) be a primary investigation of one or more intervention category; (2) be conducted in a country with a high-income economy; (3) provide information on at least one cancer screening outcome of interest; and (4) include screening use prior to intervention implementation or a concurrent group unexposed to the intervention category of interest. Forty-five studies were included in the reviews. Evidence synthesis Recommendations were added for one-on-one education to increase screening with fecal occult blood testing (FOBT) and group education to increase mammography screening. Strength of evidence for client reminder interventions to increase FOBT screening was upgraded from sufficient to strong. Previous findings and recommendations for reducing out-of-pocket costs (breast cancer screening); provider assessment and feedback (breast, cervical, and FOBT screening); one-on-one education and client reminders (breast and cervical cancer screening); and reducing structural barriers (breast cancer and FOBT screening) were reaffirmed or unchanged. Evidence remains insufficient to determine effectiveness for the remaining screening tests and intervention categories. Conclusions Findings indicate new and reaffirmed interventions effective in promoting recommended cancer screening, including colorectal cancer screening. Findings can be used in community and healthcare settings to promote recommended care. Important research gaps also are described.

Background The nuclear membrane of differentiated airway epithelial cells is a significant barrier for nonviral vectors. Trans-cyclohexane-1,2-diol (TCHD) is an amphipathic alcohol that has been shown to collapse nuclear pore cores and allow the uptake of macromolecules that would otherwise be too large for nuclear entry. Previous studies have shown that TCHD can increase lipid-mediated transfection in vitro. Methods We aimed to reproduce these in vitro studies using the cationic lipid GL67A, which we are currently assessing in cystic fibrosis trials and, more importantly, we assessed the effects of TCHD on transfection efficiency in differentiated airway epithelium ex vivo and in mouse lung in vivo using three different drug delivery protocols (nebulisation and bolus administration of TCHD to the mouse lung, as well as perfusion of TCHD to the nasal epithelium, which prolongs contact time between the airway epithelium and drug). Results TCHD (0.5–2%) dose-dependently increased Lipofectamine 2000 and GL67A-mediated transfection of 293T cells by up to 2 logs. Encouragingly, exposure to 8% TCHD (but not 0.5% or 2.0%) increased gene expression in fully differentiated human air liquid interface cultures by approximately 20-fold, although this was accompanied by significant cell damage. However, none of the TCHD treated mice in any of the three protocols had higher gene expression compared to no TCHD controls. Conclusions Although TCHD significantly increases gene transfer in cell lines and differentiated airway epithelium ex vivo, this effect is lost in vivo and further highlights that promising in vitro findings often cannot be translated into in vivo applications. Copyright © 2012 John Wiley & Sons, Ltd.

Cervical cancer is preventable with treatment of precancerous lesions and treatable at early stages. Hispanics have higher rates of cervical cancer and lower rates of screening. Ayndando a las Mujeres con Informaccion, Guia, y Amor para su Salud (AMIGAS) is an intervention to increase cervical cancer screening in U.S. women of Mexican origin. AMIGAS was developed with the participation of the community using intervention mapping (IM). Following the IM process, the authors completed a needs assessment, development of program objectives, selection of intervention methods and strategies, and program design. A benefit of IM is its linkage with community-based participatory research as it includes engagement of community members to identify and refine priority areas. The success of this strategy suggests it a useful tool for other populations. The resulting intervention program is currently being tested for efficacy and cost-effectiveness in three sites: El Paso, Texas; Houston, Texas; and Yakima, Washington.

OBJECTIVE Many studies have been conducted to understand what factors are associated with human papillomavirus (HPV) vaccine acceptability and completion of the 3-dose vaccination series, but few have examined whether people understand the survey items used to assess these relationships. Through a multisite collaborative effort, we developed and cognitively tested survey items that represent constructs known to affect vaccine acceptability and completion. MATERIALS AND METHODS Investigators from 7 research centers in the United States used cognitive interviewing techniques and in-person and telephone interviews to test 21 items. Four rounds of testing, revising, and retesting were conducted among racially and ethnically diverse parents (n = 62) of girls between the ages of 9 and 17 years. RESULTS The final survey contained 20 items on attitudes and beliefs relevant to HPV vaccine. Some parents misinterpreted statements about hypothetical vaccine harms as statements of fact. Others were unwilling to answer items about perceived disease likelihood and perceived vaccine effectiveness, because they said the items seemed to have a "right" answer that they did not know. On the basis of these and other findings from cognitive testing, we revised the wording of 14 questions to improve clarity and comprehension. We also revised instructions, response options, and item order. CONCLUSIONS Cognitive testing of HPV vaccine survey items revealed important differences between intended and ascribed item meaning by participants. Use of the tested survey questions presented here may increase measurement validity and researchers' ability to compare findings across studies and populations. Additional testing using quantitative methods can help to further validate these items.

these deaths were due to lung (31%), prostate (10%), and colorectal cancers (10%). Among women, most deaths were from lung (25%), breast (15%), and colorectal cancers (10%), with an additional 1% from cervical cancers. For breast, cervical, and colorectal cancers, routine screening is recommended by the U.S. Preventive Services Task Force (USPSTF) 3 –6 —an independent panel of experts in primary care and prevention that systematically reviews evidence of effectiveness—and by most major medical organizations. 7 Screening recommendations from the USPSTF for breast, cervical, and colorectal cancers are shown in Table 1. A 2003 report from the National Cancer Policy Board 8 noted that screening all eligible people not currently screened with USPSTFrecommended mammography, Pap smears, and colorectal cancer screening tests could prevent an additional 4475 deaths from breast cancer, 3644 deaths from cervical cancer, and 9632 deaths from colorectal cancer per year. At present, the USPSTF does not recommend screening for lung and prostate cancers because no convincing evidence shows that benefits outweigh harms. 3,9

Most major medical organizations recommend routine screening for breast, cervical, and colorectal cancers. Screening can lead to early detection of these cancers, resulting in reduced mortality. Yet not all people who should be screened are screened, either regularly or, in some cases, ever. This report presents the results of systematic reviews of effectiveness, applicability, economic efficiency, barriers to implementation, and other harms or benefits of interventions designed to increase screening for breast, cervical, and colorectal cancers by increasing community demand for these services. Evidence from these reviews indicates that screening for breast cancer (mammography) and cervical cancer (Pap test) has been effectively increased by use of client reminders, small media, and one-on-one education. Screening for colorectal cancer by fecal occult blood test has been increased effectively by use of client reminders and small media. Additional research is needed to determine whether client incentives, group education, and mass media are effective in increasing use of any of the three screening tests; whether one-on-one education increases screening for colorectal cancer; and whether any demand-enhancing interventions are effective in increasing the use of other colorectal cancer screening procedures (i.e., flexible sigmoidoscopy, colonoscopy, double contrast barium enema). Specific areas for further research are also suggested in this report.

Most major medical organizations recommend routine screening for breast, cervical, and colorectal cancers. Screening can lead to early detection of these cancers, resulting in reduced mortality. Yet not all people who should be screened are screened, either regularly or, in some cases, ever. This report presents the results of systematic reviews of effectiveness, applicability, economic efficiency, barriers to implementation, and other harms or benefits of interventions designed to increase screening for breast, cervical, and colorectal cancers by increasing community demand for these services. Evidence from these reviews indicates that screening for breast cancer (mammography) and cervical cancer (Pap test) has been effectively increased by use of client reminders, small media, and one-on-one education. Screening for colorectal cancer by fecal occult blood test has been increased effectively by use of client reminders and small media. Additional research is needed to determine whether client incentives, group education, and mass media are effective in increasing use of any of the three screening tests; whether one-on-one education increases screening for colorectal cancer; and whether any demand-enhancing interventions are effective in increasing the use of other colorectal cancer screening procedures (i.e., flexible sigmoidoscopy, colonoscopy, double contrast barium enema). Specific areas for further research are also suggested in this report. (Am J Prev Med 2008;35(1S):S34-S55) © 2008 American Journal of Preventive Medicine

The Centers for Disease Control and Prevention (CDC) is committed to achieving true improvements in people's health. In chronic disease prevention and health promotion, we have a good deal of evidence about which intervention strategies work in clinics and in communities to improve health, but we need to accelerate translating that evidence into practice. This paper provides an overview of initial efforts of the National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP) within the CDC to identify and organize the fundamental elements of translation, with the goal of understanding what our constituents need for success and to identify key issues to consider in translation.

Background Numerous agencies are providing training, technical assistance, and other support to build community-based practitioners’ capacity to adopt and implement evidence-based prevention interventions. Yet, little is known about how best to design capacity-building interventions to optimize their effectiveness. Wandersman et al. (Am J Community Psychol.50:445–59, 2102) proposed the Evidence-Based System of Innovation Support (EBSIS) as a framework to guide research and thereby strengthen the evidence base for building practitioners’ capacity. The purpose of this review was to contribute to further development of the EBSIS by systematically reviewing empirical studies of capacity-building interventions to identify (1) the range of strategies used, (2) variations in the way they were structured, and (3) evidence for their effectiveness at increasing practitioners’ capacity to use evidence-based prevention interventions. Methods PubMed, EMBASE, and CINAHL were searched for English-language articles reporting findings of empirical studies of capacity-building interventions that were published between January 2000 and January 2014 and were intended to increase use of evidence-based prevention interventions in non-clinical settings. To maximize review data, studies were not excluded a priori based on design or methodological quality. Using the EBSIS as a guide, two researchers independently extracted data from included studies. Vote counting and meta-summary methods were used to summarize findings. Results The review included 42 publications reporting findings from 29 studies. In addition to confirming the strategies and structures described in the EBSIS, the review identified two new strategies and two variations in structure. Capacity-building interventions were found to be effective at increasing practitioners’ adoption (n = 10 of 12 studies) and implementation (n = 9 of 10 studies) of evidence-based interventions. Findings were mixed for interventions’ effects on practitioners’ capacity or intervention planning behaviors. Both the type and structure of capacity-building strategies may have influenced effectiveness. The review also identified contextual factors that may require variations in the ways capacity-building interventions are designed. Conclusions Based on review findings, refinements are suggested to the EBSIS. The refined framework moves the field towards a more comprehensive and standardized approach to conceptualizing the types and structures of capacity-building strategies. This standardization will assist with synthesizing findings across studies and guide capacity-building practice and research. Electronic supplementary material The online version of this article (doi:10.1186/s13012-015-0272-7) contains supplementary material, which is available to authorized users.

The relationship between skin cancer and ultraviolet radiation is well established. Behaviors such as seeking shade, avoiding sun exposure during peak hours of radiation, wearing protective clothing, or some combination of these behaviors can provide protection. Sunscreen use alone is not considered an adequate protection against ultraviolet radiation. This report presents the results of systematic reviews of effectiveness, applicability, other harms or benefits, economic evaluations, and barriers to use of selected interventions to prevent skin cancer by reducing exposure to ultraviolet radiation. The Task Force on Community Preventive Services found that education and policy approaches to increasing sun-protective behaviors were effective when implemented in primary schools and in recreational or tourism settings, but found insufficient evidence to determine effectiveness when implemented in other settings, such as child care centers, secondary schools and colleges, and occupational settings. They also found insufficient evidence to determine the effectiveness of interventions oriented to healthcare settings and providers, media campaigns alone, interventions oriented to parents or caregivers of children, and community-wide multicomponent interventions. The report also provides suggestions for areas for future research.

The authors draw on the lessons highlighted in preceding articles in the current supplement to provide recommendations for cancer screening intervention research and to highlight some of the many questions that will require further investigation.

This study examined the breast and cervical cancer screening practices of Hispanic and non-Hispanic women (n = 3,568) in counties that approximate the US southern border region. According to the Health Resources Services Administration (HRSA), border counties are those in which any part of the county is within 100 kilometers (62.14 miles) of the border. The study used data from Behavioral Risk Factor Surveillance System (BRFSS) surveys of adults aged > or = 18 years conducted in 1999 and 2000. The study looked at recent use of mammography and the Papanicolaou (Pap) test. Hispanic women were less likely to have had a recent mammogram or Pap test as compared with non-Hispanic women in border counties, and as compared with Hispanic and non-Hispanic women in nonborder counties of Texas, New Mexico, Arizona, and California combined, and with other women in the United States. Results underscore the need for continued efforts to ensure that medically underserved women who live in the border region have access to cancer screening services.

Special events such as health fairs, cultural festivals and charity runs are commonly employed in the community to increase cancer screening; however, little is known about their effectiveness. The purpose of this study is to assess the activities, screening outcomes, barriers and recommendations of special events to increase breast, cervical and colorectal cancer screening. In-depth interviews were conducted nationally with 51 coordinators of events in June to September 2012. Health fairs and screening days were the most common events conducted, primarily for breast cancer education. Goals were to increase awareness of cancer screening and reach special populations. Evidence-based Community Guide strategies to increase cancer screening employed were: small media, reducing structural barriers, one-on-one education or group education. For each event that provided screening on-site or through referral, a mean of 35 breast, 28 cervical and 19 colorectal cancer screenings were reported. Coordinators made recommendations for further evaluation of special events, and most plan to conduct another special event. These data are novel and provide baseline documentation of activities and recommendations for a commonly used community-based cancer screening intervention that lacks evidence of effectiveness. Additional research to better understand the use of special events for increasing cancer screening is warranted.

Hispanic women have a higher incidence of cervical cancer than all other races and ethnicities. In Hispanic subgroups, Mexican American women were among the least likely to have received cervical cancer screening. In a recent RCT, Ayudando a las Mujeres con Información, Guia, y Amor para su Salud (AMIGAS) was shown to increase cervical cancer screening rates among women of Mexican descent at 6 months in all intervention arms compared to the control arm. Limited information exists about the economics of interventions to increase cervical cancer screening rates among women of Mexican descent.This study aims to estimate the cost-effectiveness of the alternative AMIGAS intervention methods for increasing cervical cancer screening among low-income women of Mexican descent in three U.S. communities.Cost data were collected from 2008 to 2011 alongside the AMIGAS study of 613 women. Receipt of Pap test within 6 months of intervention was the primary outcome measure in the cost-effectiveness analysis, conducted during 2012-2013.The cost per additional woman screened comparing the video-only intervention to usual care was $980. The cost increased to $1,309 with participant time cost included. With an additional cost per participant of $3.90 compared to flipchart only, the full AMIGAS program (video plus flipchart) yielded 6.8% additional women screened.Results on the average and incremental cost-effectiveness of the AMIGAS program elements may assist health policymakers and program managers to select and appropriately budget for interventions shown to increase cervical cancer screening among low-income women of Mexican descent.

Many barriers to cervical cancer screening for Hispanic women have been documented, but few effective interventions exist. The Community Preventive Services Task Force recommends increasing cervical cancer screening through various methods. Building on this evidence, the Centers for Disease Control and Prevention funded the research and testing phases for an evidence-based and theoretically grounded intervention designed to increase cervical cancer screening among never and rarely screened Hispanic women of Mexican descent. In this article, we describe the development process of the AMIGAS (Ayudando a las Mujeres con Información, Guía, y Amor para su Salud) intervention, highlight the integration of scientific evidence and community-based participatory research principles, and identify opportunities for dissemination, adaptation, and implementation of this intervention.The AMIGAS team was a collaboration among researchers, promotoras (community health workers), and program administrators. The multiyear, multiphase project was conducted in Houston, Texas; El Paso, Texas; and Yakima, Washington. The team completed several rounds of formative research, designed intervention materials and methodology, conducted a randomized controlled trial, created a guide for program administrators, and developed an intervention dissemination plan.Trial results demonstrated that AMIGAS was successful in increasing cervical cancer screening among Hispanic women. Adaptation of AMIGAS showed minimal reduction of outcomes. Dissemination efforts are underway to make AMIGAS available in a downloadable format via the Internet.Developing a community-based intervention that is evidence-based and theoretically grounded is challenging, time-intensive, and requires collaboration among multiple disciplines. Inclusion of key stakeholders-in particular program deliverers and administrators-and planning for dissemination and translation to practice are integral components of successful intervention design. By providing explicit directions for adaptation for program deliverers, relevant information for program administrators, and access to the intervention via the Internet, AMIGAS is available to help increase cervical cancer screening among Hispanic women and other women disproportionately affected by cervical cancer.

Background: Research suggests that evidence-based, culturally appropriate, and theoretically-based interventions promote behavior change. The process of developing such an intervention may be time and labor intensive, as well as costly. When these interventions are successful, it may be useful to adapt the intervention for a different population. Limited literature exists documenting the process of adapting cervical cancer screening interventions. AMIGAS, Ayudando a Las Mujeres con Información, Guía y Amor para su Salud, is a theoretically- and evidence-based intervention, delivered by community health workers, that was designed to increase cervical cancer screening among Latinas of Mexican descent that have been never or rarely screened for cervical cancer. A randomized controlled trial demonstrated that AMIGAS significantly increased the use of Pap tests by trial participants and was cost effective. The next step in the evolution of AMIGAS is a revision of this intervention for African American women. Community health workers can be an effective mode of health information transmission in African American communities. African American women and Latinas may share similar facilitators and barriers to cervical cancer screening, but may also have a few important differences that should be addressed in the revised intervention. Methods: A literature review was conducted to determine what facilitators and barriers to cervical cancer screening among African American women were similar to or different from Latinas. We searched MEDLINE, CINAHL, and PsychInfo for English language articles with samples that included and reported data on African American women aged 21-64, were studies conducted in the US, were focused on cervical cancer screening, and were published from 2004-2014. Findings were compared with a similar literature review conducted to assess facilitators and barriers to cervical cancer screening among Latinas. Findings: We identified 471 articles that met the inclusion criteria. Similar facilitators of cervical cancer screening for Latinas and African American women included the recognition that taking care of oneself helps the family and a supportive medical care provider. A notable facilitator for Latinas that was not evident for African American women was the presence of a supportive partner. Several similar barriers existed including limited knowledge and awareness about cervical cancer and cervical cancer screening, embarrassment, lack of insurance, and lack of child care. There were, however, a number of different barriers, not previously identified as barriers among Latinas, that warrant our attention during the adaptation process. Barriers to cervical cancer screening specific to African American women were history of trauma, fear related to the harms of screening, concerns about privacy, belief that a higher power is in control, assertion that cancer cannot be prevented, and cancer fatalism. Implications: Adapting AMIGAS for African American women will be a complex process. The evidence base and theoretical constructs for the intervention will remain the same. The revised intervention will feature materials that have been adapted to address language, literacy, health literacy, and social context and experiences, including important barriers to cervical cancer screening not identified as barriers for Latinas. The features of the intervention that are expected to be most significantly modified include logos and images and messages to address barriers to cervical cancer screening. It is expected that the resulting revised intervention will be a useful tool to increase cervical cancer screening among African American women who have rarely or never been screened for cervical cancer. Citation Format: Judith Lee Smith, Ashley Ghaffarzadeh, Katherine M. Wilson. Adaptation of an effective cervical cancer screening intervention: Assessing barriers and facilitators to screening among Latinas and African American women. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr A32.

Introduction CDC's Colorectal Cancer Control Program (CRCCP) funds 25 states and 4 tribal organizations to promote and increase colorectal cancer screening population-wide. The CRCCP grantees must use evidence-based strategies from the Guide to Community Preventive Services, including small media and client reminders. Methods To assess the existing resources and needs to promote colorectal cancer screening, we conducted 2 web-based surveys of CRCCP grantees and their community partners. Survey 1 sought to identify priority populations, the number and quality of existing colorectal cancer resources for different population subgroups, and the types of small media and client reminder they were most interested in using. Survey 2 assessed screening messages that were used in the past or might be used in the future, needs for non-English-language information, and preferences for screening-related terminology. Results In survey 1 (n = 125 from 26 CRCCPs), most respondents (83%) indicated they currently had some information resources for promoting screening but were widely dissatisfied with the quality and number of these resources. They reported the greatest need for resources targeting rural populations (62% of respondents), men (53%), and Hispanics (45%). In survey 2 (n = 57 from 25 CRCCPs), respondents indicated they were most likely to promote colorectal cancer screening using messages that emphasized family (95%), role models (85%), or busy lives (83%), and least likely to use messages based on faith (26%), embarrassment (25%), or fear (22%). Nearly all (85%) indicated a need for resources in languages other than English; 16 different languages were mentioned, most commonly Spanish. Conclusion These findings provide the first picture of CRCCP information resources and interests, and point to specific gaps that must be addressed to help increase screening.

Little is known about referrals from primary care providers (PCPs) for suspected hematologic malignancies, including their clinical triggers and frequency. A random sample of 190 Massachusetts PCPs were presented with a vignette concerning a patient with a new finding of moderate anemia, asked how they would respond, and then asked what they would do if the patient returned with persistent anemia plus one additional sign or symptom. We also asked about referral behaviors for suspected hematologic malignancies during the prior year. 134 (70.5%) PCPs responded. At first anemia presentation, only 3.8% reported referring to hematology. The development of a second sign or symptom yielded higher referral rates: pancytopenia = 88.7%, leukopenia = 63.9%, thrombocytopenia = 63.9%, lymphadenopathy = 42.9%, leukocytosis = 37.6%, night sweats = 25.6%, and weight loss = 23.3%. The median yearly number (interquartile range) of patients PCPs reported suspecting of having hematologic malignancy was 5 (3, 10), and the median formally referred was 5 (3, 10). We conclude that anemia plus signs and symptoms suggestive of myelodysplasia or leukemia (as compared to lymphoma) are more likely to prompt hematology referral. In addition, given their rarity, the number of yearly referrals suggests a satisfactory level of PCP surveillance.

The goal of cancer control research is “to generate basic knowledge about how to monitor and change individual and collective behavior and to ensure that knowledge is translated into practice and policy rapidly, effectively, and efficiently” (Division of Cancer Control and Population Sciences in Cancer control framework and synthese rationale, 2010). Research activities span the cancer control continuum from prevention to early detection and diagnosis through treatment and survivorship (Division of Cancer Control and Population Sciences in Cancer control framework and synthese rationale, 2010). While significant advancements have been made in understanding, preventing and treating cancer in the past few decades, these benefits have yielded disproportionate results in cancer morbidity and mortality across various socioeconomic and racial/ethnic subgroups (Ozols et al in J Clin Oncol, 25(1):146–1622, 2007). It has been a high priority since the beginning of the Comprehensive Cancer Control (CCC) movement to utilize research in the development and implementation of cancer plans in the states, tribes and tribal organizations, territories and US Pacific Island Jurisdictions. Nevertheless, dissemination and implementation of research in coalition activities has been challenging for many programs. Lessons learned from programs and coalitions in the implementation and evaluation of CCC activities, as well as resources provided by national partners, can assist coalitions with the translation of research into practice.

Background The recent proliferation of studies describing factors associated with HPV vaccine acceptability could inform health care providers in improving vaccine coverage and support future research. This review examined measures of HPV and HPV-vaccine knowledge, attitudes, beliefs and acceptability, described psychometric characteristics, and provided recommendations about their use. Methods A systematic search of Medline, CINAHL, PsychoInfo, and ERIC through May 2008 for English language reports of quantitative data from parents, young adults or adolescents yielded 79 studies. Results The majority of studies were cross-sectional surveys (87%), self-administered (67%), conducted before prophylactic vaccines were publicly available (67%) and utilized convenience samples (65%). Most measured knowledge (80%), general attitudes about HPV vaccination (40%), and willingness to vaccinate one's daughter (26%). Two-thirds did not report reliability or validity of measures. The majority did not specify a theoretical framework. Conclusions Use of a theoretical framework, consistent labeling of constructs, more rigorous validation of measures, and testing of measures in more diverse samples are needed to yield measurement instruments that will produce findings to guide practitioners in developing successful community and clinical interventions.

Most major medical organizations recommend routine screening for breast, cervical, and colorectal cancers. Screening can lead to early detection of these cancers, resulting in reduced mortality. Yet not all people who should be screened are screened, either regularly or, in some cases, ever. This report presents the results of systematic reviews of effectiveness, applicability, economic efficiency, barriers to implementation, and other harms or benefits of interventions designed to increase screening for breast, cervical, and colorectal cancers by increasing community demand for these services. Evidence from these reviews indicates that screening for breast cancer (mammography) and cervical cancer (Pap test) has been effectively increased by use of client reminders, small media, and one-on-one education. Screening for colorectal cancer by fecal occult blood test has been increased effectively by use of client reminders and small media. Additional research is needed to determine whether client incentives, group education, and mass media are effective in increasing use of any of the three screening tests; whether one-on-one education increases screening for colorectal cancer; and whether any demand-enhancing interventions are effective in increasing the use of other colorectal cancer screening procedures (i.e., flexible sigmoidoscopy, colonoscopy, double contrast barium enema). Specific areas for further research are also suggested in this report.

Most major medical organizations recommend routine screening for breast, cervical, and colorectal cancers. Screening can lead to early detection of these cancers, resulting in reduced mortality. Yet not all people who should be screened are screened, either regularly or, in some cases, ever. This report presents the results of systematic reviews of effectiveness, applicability, economic efficiency, barriers to implementation, and other harms or benefits of interventions designed to increase screening for breast, cervical, and colorectal cancers by increasing community access to these services. Evidence from these reviews indicates that screening for breast cancer (by mammography) has been increased effectively by reducing structural barriers and by reducing out-of pocket client costs, and that screening for colorectal cancer (by fecal occult blood test) has been increased effectively by reducing structural barriers. Additional research is needed to determine whether screening for cervical cancer (by Pap test) can be increased by reducing structural barriers and by reducing out-of-pocket costs, whether screening for colorectal cancer (fecal occult blood test) can be increased by reducing out-of-pocket costs, and whether these interventions are effective in increasing the use of other colorectal cancer screening procedures (i.e., flexible sigmoidoscopy, colonoscopy, double contrast barium enema). Specific areas for further research are also suggested in this report.

Introduction Although colorectal cancer mortality rates in the general U.S. population declined slightly from 1992 to 2000, the rates for Hispanic men and women did not. Disparity in colorectal cancer screening among Hispanics may be an important factor in the unchanged mortality trends. This study examined rates of colorectal cancer test use among Hispanic and non-Hispanic adults in the United States. Methods Using sampling weights and logistic regression, we analyzed colorectal cancer test use among 5680 Hispanic and 104,733 non-Hispanic adults aged 50 years and older who participated in the 2002 Behavioral Risk Factor Surveillance System. We estimated the percentages and adjusted odds ratios (ORs) of the respondents' reported test use by sociodemographic characteristics, health care access, and state or territory of residence. Results Hispanic respondents aged 50 and older reported having had either a fecal occult blood test within the past year or a lower endoscopy (sigmoidoscopy or colonoscopy) within 10 years less frequently (41.9%) than non-Hispanic respondents (55.2%). Rates of test use were lower for respondents who reported less education, lower income, no health insurance, and no usual source of health care, regardless of Hispanic ethnicity. After adjusting for differences in education, income, insurance, and having a usual source of health care, Hispanic respondents remained less likely than non-Hispanic respondents to report colorectal cancer testing (OR for fecal occult blood test, 0.66; 95% confidence interval [CI], 0.56–0.81; OR for lower endoscopy, 0.87; 95% CI, 0.77–0.99). Greater disparity in screening rates between Hispanics and non-Hispanics was observed in Colorado, California, and Texas than in other states. Conclusion A disparity exists between Hispanic and non-Hispanic U.S. adults in colorectal cancer test use. This disparity varies among the states, highlighting the diverse health care experience of Hispanic adults in the United States.

This article describes recruitment activities and costs from two independently conducted studies that used similar, systematic approaches to recruiting two subgroups of underscreened women, Black women and Mexican women. The studies varied in number of recruiters, venues of recruitment, and region of the country. The ratio of women approached to women who were underscreened was 4:1 for Black women and 10:1 for Mexican women. Hysterectomy was a predominant reason for ineligibility among Black women but not Mexican women. In both studies, personal networks were the most productive method of identifying women. Flyers and organized community venues were least productive. The cost incurred for identifying a woman who was eligible for a focus group was $145 for Black women and $59 for Mexican women. Those planning research or program activities that include recruiting underscreened women either to focus groups or health services could benefit from this information.

The relationship between skin cancer and ultraviolet radiation is well established. Behaviors such as seeking shade, avoiding sun exposure during peak hours of radiation, wearing protective clothing, or some combination of these behaviors can provide protection. Sunscreen use alone is not considered an adequate protection against ultraviolet radiation. This report presents the results of systematic reviews of effectiveness, applicability, other harms or benefits, economic evaluations, and barriers to use of selected interventions to prevent skin cancer by reducing exposure to ultraviolet radiation. The Task Force on Community Preventive Services found that education and policy approaches to increasing sun-protective behaviors were effective when implemented in primary schools and in recreational or tourism settings, but found insufficient evidence to determine effectiveness when implemented in other settings, such as child care centers, secondary schools and colleges, and occupational settings. They also found insufficient evidence to determine the effectiveness of interventions oriented to healthcare settings and providers, media campaigns alone, interventions oriented to parents or caregivers of children, and community-wide multicomponent interventions. The report also provides suggestions for areas for future research.

This article provides an overview of behavioral and social science cancer screening intervention research and introduces the scope of topics addressed in this supplement to Cancer. The authors identify and address issues to consider before conducting interventions to promote the uptake of screening tests, such as the benefits and harms associated with screening. Trends in the use of cancer screening tests are discussed in the context of their efficacy and adoption over time. Both the development and breadth of social and behavioral intervention research intended to increase the use of effective tests are reviewed as background for the articles that follow. The application of the lessons from this extensive knowledge base not only should accelerate the uptake of the effective cancer screening tests currently available, but also can guide future directions for research.

A large gap exists between the results of research concerning efficacious cancer screening programs and the programs delivered in practice. In this article, the authors discuss issues in, barriers to, and lessons learned regarding the dissemination of interventions. They summarize previous reviews, exemplary studies, and theories regarding the diffusion and dissemination of cancer screening interventions. Six lessons learned address the involvement of key stakeholders, factors influencing diffusion, the need for different types of efficacy and effectiveness studies with greater attention to external validity, replication, the use of theoretical and evaluation models, and the importance of policy infrastructure. In this article, the authors make recommendations for future research and practice, including improving the understanding of the intervention process and changing the types of grants funded and review criteria used. Also needed are an enhanced infrastructure, including policies to support dissemination, and the involvement of researchers, health care administrators, clinicians, and funding organizations in dissemination if the gap between research and practice in cancer screening is to be reduced.