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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.

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.

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.

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.

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 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.

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.

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.

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.

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.

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.

Women constitute about one in five hired farmworkers in the US. Their health may be affected by exposure to unhealthy living and working conditions, by increased exposure to health hazards, by poverty, and by poor utilization of health care and preventive services. About 69% of migrant and seasonal farmworkers were born outside the US, mostly in Mexico and central America, and many speak little English. The health concerns of women who are migrant and seasonal farmworkers include breast and cervical cancer, which can be prevented or controlled through routine screening, but cancer incidence and mortality data for migrant workers are sparse. We reviewed published studies that examined breast and cervical cancer screening in this population. These studies include cross-sectional surveys, health needs assessments, and randomized and non-randomized intervention trials. A review of published studies of cancer screening among women who are migrant and seasonal farmworkers indicates that underutilization of mammograms and Papanicolau (Pap) tests among this population may stem from their limited awareness of the importance of cancer screening and cultural beliefs. Other barriers include cost, lack of health insurance, lack of transportation and child care difficulties. The extent to which results obtained in selected localities are generalizable to other settings is uncertain, but results to date provide important information about possible approaches for increasing cancer screening among women migrant farmworkers.

The Division of HIV/AIDS Prevention at the National Center for HIV, Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention seeks to make evidence-based behavioral HIV prevention interventions (EBIs) accessible to HIV prevention providers through a systematic process of identification, packaging, and dissemination. This update synthesizes that process and describes recent efforts to expand the use of EBIs internationally through partnerships between the CDC's Global AIDS Program, academic research centers, and other international and US agencies.