All of Us participant perspectives on the return of value in research.

PURPOSE: To understand participant preferences for receiving specific types of research information, whether information preferences vary across sociodemographic groups, and the types of health providers participants could access to understand returned information. METHODS: All of Us Research Program participants completed a value of returning research information survey. Stratified sampling was implemented to enhance participant diversity and avoid noncoverage. We used weighted multivariable logistic regression to evaluate associations between the most valuable information types, access to providers, and sociodemographic variables. RESULTS: Participants (N = 20,405) were diverse in their race/ethnicity (eg, 52% were White, 18% were Hispanic/Latino or Spanish, 3% were Asian, and 20% were Black or African American). Most participants (78.6%) valued information about their risk of serious genetic diseases with available treatment. Primary care physicians, specialists, and genetic counselors were the top providers that participants could access for help understanding returned information. Information preferences and provider access varied across sociodemographic groups. For example, as income levels increased, the odds of placing value on genetic results indicating risk of serious disease with available treatment increased when compared with the lowest income levels (P value < .001). CONCLUSION: Although genetic information was most valuable to participants, preferences about specific information types varied across sociodemographic groups.

Adapting a conceptual framework to engage diverse stakeholders in genomic/precision medicine research.

INTRODUCTION: Genomic/precision medicine offers a remarkable opportunity to improve health and address health disparities. Genomic medicine is the study of genes and their interaction with health. Precision medicine is an approach to disease prevention and treatment that considers individual variability in genes, environment and lifestyle. Conclusions from studies lacking diversity may hinder generalizability as genomic variation occurs within and between populations. Historical factors, such as medical mistrust, ethical issues related to decision making, and data sharing pose complex challenges that may further widen inequities in genomic/precision medicine if not appropriately addressed. Although few biomedical studies integrate priorities of community partners into their conceptual framework, effective implementation of genomic/precision medicine research calls for the involvement of diverse stakeholders to expand traditional unidirectional models of engagement in clinical research towards authentic bidirectional collaboration. METHODS: A multipronged approach was used integrating an evidence-based literature review and best practices in developing and evaluating the engagement of diverse stakeholders in genomic and precision medicine research. This was combined with expert consensus building to adapt a conceptual model from a community engagement framework to addressing genomics to be scalable to engagement science, which is challenging to genomic/precision medicine research. RESULTS: The final enhanced conceptual framework is composed of four overarching dimensions now inclusive of domains in trust, exploitation, discrimination, privacy risk, stigmatization, prior harms/injustices, failure to recognize coexisting governments, intersectionality and research transformation. This conceptual framework proposes effective participant research engagement strategies for upstream relationship building, distinct from downstream recruitment strategies in which the goal is enrolment. CONCLUSION: To further shape the evolution of genomic/precision medicine research, it is important to leverage existing partnerships, engage participants beyond recruitment and embrace diverse perspectives. PATIENT OR PUBLIC CONTRIBUTION: In preparation of this manuscript, the perspectives of the community partners on the impact of engaging in genomic/precision medicine research beyond research participation were integrated into this conceptual framework from various guided listening sessions held in diverse communities.

Predictors of Participation in Clinical Research.

BACKGROUND: Despite numerous efforts to create more equitable healthcare systems, minority populations face long-standing health disparities compared to White populations. Healthcare research is the necessary foundation for creating equitable health systems and providing patient-centered care. Significant challenges exist, however, with recruiting and engaging underrepresented populations in clinical research. OBJECTIVES: The purpose of this analysis was to determine how research participants' race, trust, and level of education influence participation barriers in clinical research. METHODS: The study used secondary, cross-sectional survey data that were collected between 2014 and 2016 through the former Mid-South Clinical Data Research Network, currently known as the Stakeholders, Technology, and Research Clinical Research Network. Descriptive statistics and Spearman rank correlations were performed between level of education, level of trust, and each attitude statement for each racial category. RESULTS: A total of 2,190 survey responses were used in the data analysis. The mean age of respondents was 52 years, with majority being women, White, insured, and working full time. Overall, the respondents had favorable attitudes toward research participation. Trust was correlated with agreement in many attitude statements for both White and African American respondents, whereas correlations with education level were more variable depending on racial grouping. Trust level was negatively associated with agreement toward the statement "researchers do not care about me" in White and Native American respondents. DISCUSSION: The results support the importance of trust to research participation. Generally, education level was not strongly predictive of research participation, although prediction was influenced by race and attitude.

A Multilevel Approach to Stakeholder Engagement in the Formulation of a Clinical Data Research Network.

OBJECTIVES: To ensure meaningful engagement of stakeholders (patients, clinicians, and communities) in developing the Mid-South Clinical Data Research Network (MS-CDRN), we implemented a comprehensive, multilevel approach: (1) identify barriers to involving stakeholders in governance, network design, and implementation; (2) engage stakeholders in priority setting and research topic generation; (3) develop strategies to fully integrate stakeholders in CDRN governance and oversight; and (4) solicit guidance on patient-centered tools and strategies for recruiting research participants. METHODS: We engaged stakeholders: (1) as integral research team members; (2) on oversight and advisory committees; (3) as consultants (using Community Engagement Studios); and (4) through interviews and surveys. We recruited stakeholders from community health centers, churches, barbershops, health fairs, a volunteer registry, and a patient portal. We prioritized recruitment from populations often underrepresented in research. RESULTS: During the first 18 months, we engaged 5670 stakeholders in developing the MS-CDRN. These were research team members and on governance committees (N=10), consultants (N=58), survey respondents (N=5543), and interviewees (N=59). Stakeholders identified important barriers and facilitators to engagement, developed stakeholder-informed policies, provided feedback on priority topics and research questions, and developed an intake process for data requests and interventional studies that included reviewing for appropriate patient-centeredness, patient engagement, and dissemination. DISCUSSION: Multilevel stakeholder engagement is a novel systematic approach to developing a meaningful patient-centered and patient-engaged research program. This approach allows ongoing input from highly engaged stakeholders while leveraging focused input from larger, more diverse groups to enhance the patient-centeredness of research and increase relevance to broader audiences.

Clinicians' perspectives on and interest in participating in a clinical data research network across the Southeastern United States.

BACKGROUND: Partnerships between clinicians and researchers could increase the generalizability of research findings and increase uptake of research results across populations. Yet engaging clinicians in research is challenging. Clinical Data Research Networks (CDRNs) provide access to a broad array of clinical data, patients, clinicians and health systems by building on existing health records (EHRs) to facilitate multi-site community engaged research (CEnR). METHODS: A mixed-methods sequential explanatory design was employed. Sixty semi-structured interviews with clinicians from various disciplines and healthcare settings were conducted using five open-ended questions. Inductive content analysis was used to identify emerging themes in the data. RESULTS: We identified the following emerging themes: 1) Research with relevance and benefits to clinics and provider's patient population; 2) Difficulties of engaging in research with existing patient care demands; 3) Clear and continuous two-way communication about research, coordinated with provider and clinic needs; 4) Tailored compensation approaches meet provider preferences; 5) Increasing clinician awareness about Clinical Data Research Networks (CDRNs). CONCLUSION: Our interview study provides insight into community clinician perspectives on Clinical Data Research Networks, indicating motivations and challenges to research involvement including consequences of time spent on research participation, barriers to expanding research and meaningful involvement in research governance. Findings can be used to guide the development of strategies to better engage providers in research in clinical settings, which could ultimately improve patient outcomes.

Needs, Priorities, and Recommendations for Engaging Underrepresented Populations in Clinical Research: A Community Perspective.

Engaging underrepresented groups in outcomes research is a public health priority for reducing health and health care disparities; yet, engaging these groups is challenging. Failure to involve these underrepresented populations in research further exacerbates these disparities. This article presents the health and research priorities of diverse groups of underrepresented populations in biomedical research, their concerns for participating in research, and strategies to engage them in their healthcare and research studies. Eleven community listening sessions, ranging from 7 to 13 community members each (N = 117), representing racial/ethnic minority, economically disadvantaged (e.g., uninsured), and hearing impaired communities. We used an inductive, qualitative content analysis approach to analyze the data for emerging themes. We identified the following themes: Uncertainties of underrepresented populations regarding research participation; Ineffective communication about research opportunities and research findings; Research on primary care and prevention are priorities for underrepresented populations in research; and Research teams need training in cultural competence and humility. Underrepresented groups provided research priorities, concerns, and strategies to engage them in their healthcare and in research studies. Findings from this study could facilitate improvement of research participation among underrepresented groups, ultimately reducing health disparities and improving quality of life among groups commonly omitted from research recruitment and participation.

Type 2 diabetes and mammographic breast density among underserved women.

PURPOSE: We conducted a study of women recruited at Meharry Medical College, a historically black medical school, to investigate the relationship between diabetes and mammographic breast density. METHODS: A total of 476 women completed in-person interviews, body measurements, and full-field digital mammograms on a Hologic mammography unit from December 2011 to February 2014. Average percent breast density for the left and right breasts combined was estimated using Quantra, an automated algorithm for volumetric assessment of breast tissue. The prevalence of type 2 diabetes was determined by self-report. RESULTS: After adjustment for confounding variables, the mean percent breast density among premenopausal women with type 2 diabetes [[Formula: see text] 13.8 %, 95 % confidence interval (CI) 11.6-15.9] was nonsignificantly lower than that of women without type 2 diabetes ([Formula: see text] 15.9 %, 95 % CI 15.0-16.8) (p = 0.07); however, there was no association among postmenopausal women. The effect of type 2 diabetes in severely obese women (BMI ≥ 35) appeared to differ by menopausal status with a reduction in mean percent breast density in premenopausal women, but an increase in mean percent breast density in postmenopausal women which could have been due to chance. CONCLUSIONS: Confirmation of our findings in larger studies may assist in clarifying the role of the insulin signaling breast cancer pathway in women with high breast density.

Use of nonsteroidal anti-inflammatory drugs and reduced breast cancer risk among overweight women.

Chronic inflammation is associated with increased risk of multiple cancers, including breast cancer. Adipose tissues produce proinflammatory cytokines, and obesity is a risk factor for postmenopausal breast cancer. We evaluated the association of regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) with breast cancer risk, overall and by body mass index (BMI) and tumor subtypes defined by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status. We conducted a population-based, case-control study involving 5,078 women aged 25-75 years who were recruited primarily from the Nashville metropolitan area of Tennessee. Multivariate unconditional logistic regression models were used to estimate odds ratios and 95 % confidence intervals for breast cancer risk after adjusting for multiple potential confounding factors. Regular use of any NSAID was associated with significantly reduced breast cancer risk (OR 0.78; 95 % CI 0.69-0.89). This association was observed for regular use of baby aspirin only (OR 0.82, 95 % CI 0.69-0.99), other NSAIDs only (OR 0.81, 95 % CI 0.69-0.95), and both baby aspirin and other NSAIDs (OR 0.52, 95 % CI 0.40-0.69). These significant inverse associations were found among overweight women (BMI ≥25 kg/m(2)) overall and by subtypes of breast cancer, but not among women with BMI <25 kg/m(2) (P for interaction = 0.023). Regular use of NSAIDs was inversely associated with breast cancer risk, particularly among overweight women. Overweight women may benefit more from the protective effects of NSAID use than normal-weight women.

2021 Community Engagement Studio Virtual Training Summit: Increasing the Diversity of Stakeholders Engaged in Research.

BACKGROUND: There are few methods that focus on engaging racial and ethnic minorities in research. The Meharry-Vanderbilt Community Engaged Research Core partnered with the University of Utah, the University of Michigan, and community/patient partners to convene a virtual summit to share the Community Engagement Studio (CE Studio) model, a structured and widely-used approach that facilitates community engagement in research. OBJECTIVES: The CE Studio Virtual Training Summit (Summit) goal was to prepare multi-stakeholder (e.g., researchers, community members) research teams to engage more racial/ethnic minorities in CE studios. METHODS: Summit planning included (1) agenda development, including CE Studio training and a live CE Studio demonstration; (2) summit advertisement across several networks, including minority-serving institutions; and (3) development of pre-and post-Summit evaluations. RESULTS: Among 50 registrants (76.7% academicians) that completed evaluations, more than 65% planned to increase engagement of racial/ethnic minorities in research and implement CE Studios as a result of the Summit. Increased confidence in all CE training areas was reported, including in conducting an effective CE Studio planning meeting (32.1% pre-Summit/90.3% post-Summit) and identifying and preparing patient/community stakeholders for engagement as CE Studio experts (46.4% pre-Summit/93.6% post-Summit). CONCLUSIONS: Virtual CE Studio training that includes multi-stakeholder planning partners can be an effective method for introducing the CE Studio model and preparing multi-stakeholder research teams to engage racial and ethnic minorities in CE Studios. This is particularly salient given that effective community engaged research methods and best practices are not currently being distributed through research programs at a pace consistent with the demands.

Integrating participants as partners in research governance and operations: an approach from the All of Us Research Program Engagement Core.

OBJECTIVES: During the last two decades, researchers and funders increasingly recognised the value of engaging patients and communities in research. Despite progress, community engagement remains challenging. There are few examples of successful participant engagement in governance of large-scale research programmes. Here we describe efforts to engage participants as partners in new governance roles in the All of Us Research Program, a precision medicine research initiative which intends to enrol at least one million participants. Using intentional, participant-centric engagement strategies, the All of Us Engagement Core recruited and integrated a diverse group of participants into governance roles including Steering and Executive Committees. Evaluation measures included a survey to assess Consortium Members' readiness for participant engagement. RESULTS: Over a 3-year period, all items on the survey increased (higher readiness). Of the 291 respondents to the 2021 survey, respondents most frequently agreed that participant perspectives are essential (100%), participants understand enough to contribute meaningfully (94%) and participants should be involved in setting goals (96%). Respondents least frequently agreed that participants should have an equal voice in Working Groups (75%), Steering Committee (69%) and Executive Committee (63%). CONCLUSION: In conclusion, participants can be effectively integrated into large-scale research governance, which is associated with increased researcher readiness for engagement.

Stakeholder engagement infrastructure to support multicenter research networks: Advances from the clinical research networks participating in PCORnet.

Background: The evidence based on the inclusion of patients and other stakeholders as partners in the clinical research process has grown substantially. However, little has been reported on how stakeholders are engaged in the governance of large-scale clinical research networks and the infrastructure used by research networks to support engagement in network-affiliated activities. Objectives: The objective was to document engagement activities and practices emerging from Clinical Research Networks (CRNs) participating in PCORnet, the National Patient-Centered Clinical Research Network, specifically regarding governance and engagement infrastructure. Methods: We conducted an environmental scan of PCORnet CRN engagement structures, assets, and services, focusing on network oversight structures for policy development and strategic decision-making. The scan included assets and services for supporting patient/stakeholder engagement. Data were collected by searching web-based literature and tool repositories, review of CRN Engagement Plans, analysis of previously collected key informant interviews, and CRN-based iterative review of structured worksheets. Results: We identified 87 discrete engagement structures, assets, and services across nine CRNs. All CRNs engage patients/stakeholders in their governance, maintain workgroups and/or staff dedicated to overseeing engagement strategies, and offer one or more services to non-CRN researchers to enhance conducting engaged clinical research. Conclusions: This work provides an important resource for the research community to explore engagement across peers, reflect on progress, consider opportunities to leverage existing infrastructure, and identify new collaborators. It also serves to highlight PCORnet as a resource for non-CRN researchers seeking to efficiently conduct engaged clinical research and a venue for advancing the science of engagement.

Innovation in Large-Scale Research Programs: Elevating Research Participants to Governance Roles Through the All of Us Research Program Engagement Core.

PROBLEM: Despite the successes of community-engaged research in advancing research relevance and health equity for diverse communities, the impact of this research has been limited to local and regional programs. Engaging diverse community voices in large-scale, national research programs represents a paradigm shift in biomedical research. Still, disconnects remain between research decision makers and the communities they serve, impeding richer, bidirectional engagement. APPROACH: An engagement core team was established within National Institutes of Health All of Us Research Program (AoURP) in 2018 to synthesize community-engaged research practices and establish infrastructure that operationalizes diverse research participant engagement. The authors integrated research participants as "participant partners" within the AoURP governance, an approach that is embedded into the engagement core's 3 aims: (1) integrate a diverse pool of participants into the program, (2) identify and meaningfully engage a cadre of diverse participants into program governance, and (3) assess the impact of such engagement on research. Participant partners are compensated as consultants at approximately $50/hour. OUTCOMES: As of August 2022, more than 515,000 individuals consented to participate in the AoURP, with more than 49% representing racial/ethnic minorities. The authors invited participants to self-nominate if interested in engaging in research working groups, decision making, and governance. Also, consortium partners nominated individuals on AoURP community advisory and/or participant advisory boards to serve as participant ambassadors. Ten individuals were selected as participant partners for the 2022-2025 term. Eight serve on the steering committee; of those, 4 serve on the executive committee; 2 more serve on the advisory panel. An additional 23 serve as participant ambassadors. NEXT STEPS: The authors continue to increase the number of research participants serving as engaged partners in the program. Engagement approaches will be systematically evaluated with the goal of adoption by other large-scale research programs.

Well-done meat intake and meat-derived mutagen exposures in relation to breast cancer risk: the Nashville Breast Health Study.

Previous studies of the association of meat intake and meat-derived mutagen exposure with breast cancer risk have produced inconsistent results. We evaluated this association in a population-based case-control study of incident breast cancer conducted in Nashville, Tennessee, United States, including 2,386 breast cancer cases and 1,703 healthy women controls. Telephone interviews were conducted to obtain information related to meat intake including amount, cooking methods, and doneness levels, as well as other known or hypothesized risk factors for breast cancer. Unconditional logistic regression was used to derive odds ratios (ORs) after adjusting for potential confounders. High intake of red meat was associated with a significantly elevated risk of breast cancer (P-trend < 0.001). The association was particularly strong for high intake of well-done red meat (P-trend < 0.001), with an adjusted OR of 1.5 (95% CI = 1.3-1.9) for the highest versus the lowest quartile. Associations between red meat and breast cancer risk were slightly stronger for postmenopausal women than for premenopausal women. Meat-derived mutagens such as 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline, were significantly associated with increased breast cancer risk among postmenopausal women only (P-trend = 0.002 and 0.003, respectively). The results from this study provide strong support for the hypotheses that high red meat intake and meat-derived mutagen exposure may be associated with an increase in breast cancer risk.

Transdisciplinary Perspectives on Precision Medicine.

Purpose: The Precision Medicine Health Disparities Collaborative fosters collaboration between researchers with diverse backgrounds in precision medicine and health disparities research, to include training at the interface between genomics and health disparities. Understanding how perceptions about precision medicine differ by background may inform activities to better understand such differences. Methods: We conducted a cross-sectional survey of Center members and beyond. Data were collected on categories of educational background, current activities, and level of agreement with 20 statements related to genomics and health disparities. Respondents categorized their background and activities as social/behavioral, genetics, both, or neither. Fisher's exact test was used to assess levels of agreement in response to each statement. Statistically significant associations were further analyzed using ordinal logistic regression adjusting for age, self-identified race/ethnicity, and gender. Results: Of 130 respondents, 50 (38%) identified educational backgrounds and current activities as social-behavioral or genomic 55 (42%). Respondents differed by educational background on the statement Lifestyle and other life experiences influence how genes impact disease risk (p=0.0009). Respondents also differed by current activities on the statement Reducing disparities in access to health care will make precision medicine more effective (p=0.0008), and on Racism and discrimination make me concerned about how genetic test results will be used (p=0.0011). Conclusions: Respondents who differed on prior education and current activities, whether social behavioral science or human genomics, were associated with different perceptions regarding precision medicine and health disparities. These results identify potential barriers and opportunities to strengthen transdisciplinary collaboration.

Recognizing Cross-Institutional Fiscal and Administrative Barriers and Facilitators to Conducting Community-Engaged Clinical and Translational Research.

PURPOSE: This qualitative study examined fiscal and administrative (i.e., pre- and post-award grants process) barriers and facilitators to community-engaged research among stakeholders across 4 Clinical and Translational Science Awards (CTSA) institutions. METHOD: A purposive sample of 24 key informants from 3 stakeholder groups-community partners, academic researchers, and research administrators-from the CTSA institutions at the University of North Carolina at Chapel Hill, Medical University of South Carolina, Vanderbilt University Medical Center, and Yale University participated. Semistructured interviews were conducted in March-July 2018, including questions about perceived challenges and best practices in fiscal and administrative processes in community-engaged research. Transcribed interviews were independently reviewed and analyzed using the Rapid Assessment Process to facilitate key theme and quote identification. RESULTS: Community partners were predominantly Black, academic researchers and research administrators were predominantly White, and women made up two-thirds of the overall sample. Five key themes were identified: level of partnership equity, partnership collaboration and communication, institutional policies and procedures, level of familiarity with varying fiscal and administrative processes, and financial management expectations. No stakeholders reported best practices for the institutional policies and procedures theme. Cross-cutting challenges included communication gaps between stakeholder groups; lack of or limits in supporting community partners' fiscal capacity; and lack of collective awareness of each stakeholder group's processes, procedures, and needs. Cross-cutting best practices centered on shared decision making and early and timely communication between all stakeholder groups in both pre- and post-award processes. CONCLUSIONS: Findings highlight the importance of equitable processes, triangulated communication, transparency, and recognizing and respecting different financial management cultures within community-engaged research. This work can be a springboard used by CTSA institutions to build on available resources that facilitate co-learning and discussions between community partners, academic researchers, and research administrators on fiscal readiness and administrative processes for improved community-engaged research partnerships.

KL2 mentored career development programs at clinical and translational science award hubs: Practices and outcomes.

INTRODUCTION: NIH Clinical and Translational Science Awards (CTSAs) include KL2 mentored career development awards for faculty commencing clinical and translational research. A survey of KL2 leaders revealed program practices, curricular elements and compelling data about scholar characteristics and outcomes. METHODS: We conducted a literature review, framed the survey construct, and obtained input from across the CTSA consortium. A REDCap survey was emailed in fall 2016 to 61 active programs. RESULTS: Fifty-five programs (90.2%) responded. Respondents had been funded from 3 to 11 years, including 22 "mature" hubs funded for ≥8 years. Program cohort sizes were 56% "small", 22% "medium", and 22% "large." Hubs offer extensive competency-aligned training opportunities relevant to clinical and translational research, including graduate degrees, mentorship, and grant-writing. Seventy-two percent of hubs report parallel "KL2-equivalent" career development programs. All hubs share their training and facilitate intermingling with other early stage investigators. A total of 1,517 KL2 scholars were funded. KL2 awardees are diverse in their disciplines, research projects, and representation; 54% are female and 12% self-identified as underrepresented in biomedical research. Eighty-seven percent of scholars have 2-3 mentors and are currently supported for 2-3 years. Seventy-eight percent of alumni remain at CTSA institutions in translational science. The most common form of NIH support following scholars' KL2 award is an individual career development award. CONCLUSIONS: The KL2 is a unique career development award, shaped by competency-aligned training opportunities and interdisciplinary mentorship that inform translational research pathways. Tracking both traditional and novel outcomes of KL2 scholars is essential to capture their career trajectories and impact on health.

Energy balance, physical activity, and cancer risk.

This chapter posits that cancer is a complex and multifactorial process as demonstrated by the expression and production of key endocrine and steroid hormones that intermesh with lifestyle factors (physical activity, body size, and diet) in combination to heighten cancer risk. Excess weight has been associated with increased mortality from all cancers combined and for cancers of several specific sites. The prevalence of obesity has reached epidemic levels in many parts of the world; more than 1 billion adults are overweight with a body mass index (BMI) exceeding 25. Overweight and obesity are clinically defined indicators of a disease process characterized by the accumulation of body fat due to an excess of energy intake (nutritional intake) relative to energy expenditure (physical activity). When energy intake exceeds energy expenditure over a prolonged period of time, the result is a positive energy balance (PEB), which leads to the development of obesity. This physical state is ideal for intervention and can be modulated by changes in energy intake, expenditure, or both. Nutritional intake is a modifiable factor in the energy balance-cancer linkage primarily tested by caloric restriction studies in animals and the effect of energy availability. Restriction of calories by 10 to 40% has been shown to decrease cell proliferation, increasing apoptosis through anti-angiogenic processes. The potent anticancer effect of caloric restriction is clear, but caloric restriction alone is not generally considered to be a feasible strategy for cancer prevention in humans. Identification and development of preventive strategies that "mimic" the anticancer effects of low energy intake are desirable. The independent effect of energy intake on cancer risk has been difficult to estimate because body size and physical activity are strong determinants of total energy expenditure. The mechanisms that account for the inhibitory effects of physical activity on the carcinogenic process are reduction in fat stores, activity related changes in sex-hormone levels, altered immune function, effects in insulin and insulin-like growth factors, reduced free radical generation, and direct effect on the tumor. Epidemiologic evidence posits that the cascade of actions linking overweight and obesity to carcinogenesis are triggered by the endocrine and metabolic system. Perturbations to these systems result in the alterations in the levels of bioavailable growth factors, steroid hormones, and inflammatory markers. Elevated serum concentrations of insulin lead to a state of hyperinsulinemia. This physiological state causes a reduction in insulin-like growth factor-binding proteins and promotes the synthesis and biological activity of insulin-like growth factor (IGF)-I, which regulates cellular growth in response to available energy and nutrients from diet and body reserves. In vitro studies have clearly established that both insulin and IGF-I act as growth factors that promote cell proliferation and inhibit apoptosis. Insulin also affects on the synthesis and biological availability of the male and female sex steroids, including androgens, progesterone, and estrogens. Experimental and clinical evidence also indicates a central role of estrogens and progesterone in regulating cellular differentiation, proliferation, and apoptosis induction. Hyperinsulinemia is also associated with alterations in molecular systems such as endogenous hormones and adipokines that regulate inflammatory responses. Obesity-related dysregulation of adipokines has the ability to contribute to tumorigenesis and tumor invasion via metastatic potential. Given the substantial level of weight gain in industrialized countries in the last two decades, there is great interest in understanding all of the mechanisms by which obesity contributes to the carcinogenic process. Continued focus must be directed to understanding the various relationships between specific nutrients and dietary components and cancer cause and prevention. A reductionist approach is not sufficient for the basic biological mechanisms underlying the effect of diet and physical activity on cancer. The joint association between energy balance and cancer risk are hypothesized to share the same underlying mechanisms, the amplification of chemical mediators that modulate cancer risk depending on the responsiveness to those hormones to the target tissue of interest. Disentangling the connection between obesity, the insulin-IGF axis, endogenous hormones, inflammatory markers, and their molecular interaction is vital.

Breast cancer knowledge and barriers to mammography in a low-income managed care population.

BACKGROUND: Low-income women experience multiple barriers to screening mammography. This study explored cancer knowledge as a point of intervention to reduce overall barriers. METHODS: A survey of breast cancer knowledge and barriers was obtained from 173 low-income female residents of Middle Tennessee, > or =40 years, enrolled in the state managed care organization and nonadherent to mammography. Multiple regression models examined the effect of breast cancer knowledge on mammography screening barriers. RESULTS: Comprehensive breast cancer knowledge, not mere screening awareness, was the strongest contributor towards lower barrier scores. CONCLUSIONS: Strategies to overcome mammography barriers should include comprehensive breast cancer education.

The Impact of an Educational Video on Clinical Trial Enrollment and Knowledge in Ethnic Minorities: A Randomized Control Trial.

Introduction: Innovative methods to increase awareness about clinical trials and address barriers associated with low participation among racial/ethnic minorities are desperately needed. African Americans comprise 5% of all clinical trial participants, and Hispanics make up 1%. Use of multimedia educational material has shown promise as an effective strategy to increase minority clinical trial enrollment. However, this approach has not been broadly implemented. We tested the effect of a video educational program on clinical trial knowledge and enrollment in a sample of oncology outpatients. Methods: A randomized controlled trial was conducted with 63 oncology patients without previous history of clinical trial participation. Participants were randomly assigned to the intervention, to watch a clinical trial educational video in the office, or to the control group which did not receive in-office education. The Clinical Trial Knowledge survey was administered before the intervention and 1 week after the intervention. Participation in clinical trials was assessed 1-year post study participation. Results for white participants and ethnic minorities were compared. Ethnicity was self-reported through the electronic health record and confirmed by self-reporting on questionnaire. Results: Sixty-three participants were recruited in this study. At 1-year follow-up, 3 participants enrolled in clinical trials in the study group which had received office-based video intervention and 2 participants enrolled in the control group (Z = 0.39, p = 0.69). These results were not statistically significant. Impact of the intervention by ethnicity could not be assessed due to low total clinical trial enrollment. The video intervention did not change knowledge, attitudes, or barriers as measured by the Clinical Trial Knowledge Survey. Minority participants did report significantly more negative beliefs and barriers to participation than white participants. Conclusions: Increasing awareness and knowledge about clinical trials in underrepresented communities is an important step to providing opportunities for participation. Future studies should focus on how to address the negative expectations of clinical trials and the greater information needs in minority populations. Tailored or personalized messaging may address negative perceptions of clinical trial participation.

Transition to Independence: Characteristics and Outcomes of Mentored Career Development (KL2) Scholars at Clinical and Translational Science Award Institutions.

PURPOSE: To describe the transition from mentored to independent research funding for clinical and translational scholars supported by institutional KL2 Mentored Career Development programs. METHOD: In 2013, faculty leaders at Clinical and Translational Science Award institutions completed an online survey, reporting characteristics of scholars in their KL2 programs from 2006 to 2013. The primary outcome variable was a report that the scholar had received independent funding as a principal investigator. Data analysis included descriptive summaries and mixed-effects regression models. RESULTS: Respondents from 48 institutions (of 62 eligible; 77%) provided information about 914 KL2 scholars. Of those, 620 (68%) were medical doctors, 114 (12%) had other clinical training, and 177 (19%) were nonclinician PhDs. Fifty-three percent (487) were female; 12% (108/865) were members of racial or ethnic groups underrepresented in medicine (URM). After completing KL2 training, 96% (558/582) remained engaged in research. Among scholars who completed KL2 training two or more years earlier, 39% (149/374) received independent funding. Independent funding was from non-National Institutes of Health (NIH) sources (120 scholars) more often than from NIH (101 scholars). The odds of a nonclinician attaining independent funding were twice those of a clinician (odds ratio 2.05; 95% confidence interval 1.11-3.78). Female and URM scholars were as likely as male and non-URM scholars to attain independent funding. CONCLUSIONS: KL2 programs supported the transition to independent funding for clinical and translational scientists. Female and URM scholars were well represented. Future studies should consider non-NIH funding sources when assessing the transition to research independence.