The biomedical workforce continues to lack diversity, despite growing evidence demonstrating the advantages of diverse teams in workplaces for creativity and innovation. At the University of Pittsburgh Institute for Clinical Research Education, we have taken a multi-pronged, collaborative approach to enhance the diversity of our trainees and scholars. We started by implementing a program for postdoctoral fellows and junior faculty, the Career Education and Enhancement for Health Care Research Diversity (CEED) program. We then built on this program and created a sister program for medical students (CEED II). These two programs were intended to build a local community of diverse researchers. Following the success of these programs, we extended our efforts and pursued federal funding to establish other programs. Our first funded program was designed to teach leadership and career coaching skills to mentors who are committed to mentoring people from diverse backgrounds, the Professional Mentoring Skills Enhancing Diversity (PROMISED) program. We then partnered with minority serving institutions to create a fellowship in translational research skills training, Leading Emerging and Diverse Scientists to Success (LEADS), training in patient-centered outcomes research, Expanding National Capacity in PCOR through Training (ENACT), and a year-long fellowship to work with a specific mentor at Pitt, the Clinical and Translational Science (CTS) Fellowship (TL1). With recognition that much work remains to be done, we believe these programs represent a small but positive step toward diversifying the biomedical workforce. A recent Google report describes the underrepresentation of women and ethnic minorities in STEM  fields as “a serious impediment to technological innovation as well as an affront to fundamental notions of fairness and equity”  (p. 3). There is a growing body of literature on workforce diversification outside of biomedicine, for example, in the fields of human services management and occupational and organizational psychology ,4,5,6. TAlthough progress to rectify this situation has been slow, research is pointing the way toward solutions. A meta-analysis by Rodriguez et al.  offers rThis is the approach we have taken at the University of Pittsburgh Institute for Clinical Research Education, where we have developed a number of programs that target workforce diversification from multiple angles, including recruitment of URB scholars, training in the informal curriculum, peer support structures to enhance retention, mentor training, cross-institutional networking opportunities, fellowships, and travel grants. To ensure that our approach is guided by the experiences and recommendations of URB scientists, we have developed some of these programs in partnership with Minority Serving Institutions (MSIs). In this paper, we will briefly describe the rationale, design, and preliminary outcomes of six workforce diversification programs, the Career Education and Enhancement for Health Care Research Diversity programs (CEED and CEED II), the Clinical and Translational Science (CTS) Fellowship (TL1), the Leading Emerging and Diverse Scientists to Success program (LEADS), the Professional Mentoring Skills Enhancing Diversity program (PROMISED), and the Expanding National Capacity in PCOR through Training program (ENACT), as well as future plans.Established in 2005, the Institute for Clinical Research Education (ICRE), housed within the University of Pittsburgh School of Medicine, has seven degree programs and 12 career development programs for trainees across the career pipeline, from medical and graduate students to faculty. Diversity has always been one of the ICRE’s top priorities, which is why we have trained 318 (27%) URB scientists over the last 10 years . Of these, 91% are still involved in research, 89% remain in academia, and 37% have stayed at the University of Pittsburgh—clear evidence of the effectiveness of ICRE efforts at both recruitment and retention. Over the past year we trained a total of 119 URB individuals, or 34% of all of our trainees . As of July 2018, 40% of our career development trainees and 14% of our degree students are from underrepresented backgrounds.Six of our programs are directly concerned with neutralizing the barriers faced by many minorities in achieving a career in biomedical science. These barriers, as identified by the Sullivan Commission Task Force on Racial and Ethnic Diversity within the Schools of the Health Sciences at the University of Pittsburgh , includeWe are constantly seeking ways to increase the number of individuals from underrepresented backgrounds in most of our training programs—as with LEADS, for example, which we expect to grow as we recruit additional MSIs. However, it is important to recognize that all of these programs are competitive, and some (such as CEED and CEED II) are not meant to grow beyond current enrollment because of our intent to provide a personalized experience. The ICRE Diversity Committee plays an integral role in these efforts, bringing together faculty members with significant experience and leadership roles from multiple schools and departments at Pitt to help in the recruitment, support, and mentorship of trainees from diverse backgrounds. The committee meets monthly to refine and advance our diversity efforts, with a particular focus on transitioning trainees into academic careers at Pitt. Our recruitment efforts are further aided by partnerships with the Office of Health Sciences Diversity and the School of Medicine’s Office of Student Affairs/Diversity Programs. Additionally, we collaborate with the Center for Health Equity at the Graduate School of Public Health and the Center for Heath Equity Research and Promotion at the Veterans Affairs Pittsburgh Healthcare System to provide educational and mentoring support to trainees interested in research on health disparities. The following six programs are specifically focused on workforce diversification:Pololi et al.  have fouOffered exclusively to URB junior faculty and postdoctoral researchers, CEED provides mentoring and training in scientific and grant writing, research presentation, and other skills required to apply for competitive career development awards or other types of grant funding. The program includes a monthly seminar series, multilevel mentoring, targeted coursework, and networking opportunities to promote success in academic research for URB researchers. Recognizing that the pipeline for URB researchers begins early in students’ educational trajectories, the CEED II program was created in 2012 with the aim of encouraging URB medical students to pursue a research career in clinical and translational science. Students are invited to attend presentations on increasing productivity, giving presentations, writing with clarity, and setting and meeting realistic goals. Students also meet regularly with their mentor and the program director to set personalized goals.Four of our other programs were created in partnerships with a number of Minority Serving Institutions. We view these partnerships as an exciting development and the guidance of leaders from our partner MSIs helps to ensure that our programs are culturally appropriate and tailored to the needs of URB scientists. Moreover, the partnerships themselves have created cross-institutional professional networks that increase opportunities for collaboration among our trainees.The Clinical and Translational Science (CTS) Fellowship (TL1) (grant number TL1TR001858), has partnered with the Research Centers in Minority Institutions (RCMI) Translational Research Network (RTRN) to actively recruit trainees from 18 MSIs, in an effort to expand program diversity. The TL1 fellowship provides pre- and post-doctoral trainees with a personalized, one-year fellowship based on their particular phase of translational research (T1–T4). The fellowship is open to trainees from all academic schools, including engineering and arts and sciences, and can train up to 10 pre-doctoral and 10 post-doctoral trainees at any time. Fellows conduct one or more mentored translational research projects, aided by the following: (1) Career development training in entrepreneurship, team science, writing, stakeholder engagement, and managing a research career, (2) rigorous research training, and (3) a multidisciplinary mentoring team. By specifically recruiting trainees from MSIs, this program seeks to expand URB representation in translational research and provide training and support to improve retention.The Professional Mentoring Skills Enhancing Diversity (PROMISED) program was funded by the National Research Mentoring Network (NRMN), part of the NIH Diversity Consortium (grant number U54GM119023). PROMISED promotes workforce diversity through online professional skill development for mentors who are explicitly committed to mentoring scientists from diverse backgrounds. The program is designed to help mentors develop critical leadership skills and incorporate career coaching principles into their mentoring. It consists of a two-day intensive training program in Pittsburgh facilitated by career coaches, followed by a year-long fellowship involving online modules with weekly assignments, discussions, and synchronous meetings. Modules address topics such as strategic planning, assessing strengths and weaknesses, understanding academic culture, and time management. This training prepares mentors to navigate their institutions more effectively, and thereby more effectively help URB mentees do the same.The Leading Emerging and Diverse Scientists to Success (LEADS) program is a year-long Fellowship in Translational Research designed to meet the needs of junior faculty and post-doctoral fellows from eight partnering MSIs . It is funded by an Innovative Programs to Enhance Research Training (IPERT) grant from the National Institute of General Medical Sciences (NIGMS) (grant number R25GM116740).LEADS offers month-long, instructor-led online training modules in critical skill areas, ranging from team science to grantsmanship, and from medical writing to critical and creative thinking. Each module involves assignments designed to help trainees create a meaningful work product . The program also provides travel awards for fellows to disseminate their research. Designated senior faculty members from each participating institution are trained to advise and support fellows as they build their biomedical research careers. Additionally, beginning in 2018, we instituted an annual summit. Travel and related expenses are covered for both LEADS leadership and scholars. Hosted in collaboration with the University of Puerto Rico (a LEADS partnering institution), the summit brought together collaborators from seven partnering MSIs, as well as a majority of participating LEADS scholars, for career development and networking opportunities.We have recently accepted our third cohort of diverse scholars who are pursuing research in a wide range of areas, from behavioral to basic and even community-engaged research. LEADS participants gain skills that will contribute to their professional advancement. They also have opportunities through the program and the leadership summit to develop support networks and collaborations with URB scholars at other institutions. We believe that both will contribute to the goal of improving the retention of URB scholars in the biomedical workforce.Expanding National Capacity in PCOR through Training (ENACT) is a tuition-free program that provides investigators from six partnering MSIs with training in Patient-Centered Outcomes Research (PCOR). Funded by the Agency for Healthcare Research and Quality (AHRQ) (grant number R25HS023185), ENACT offers two online courses in PCOR that prepare participants to write a PCOR-focused proposal. It also provides a one-year fellowship (with five spots available per year) that funds two intensive, experiential PCOR training visits to Pittsburgh, in addition to the online courses. The two-week visits provide fellows with designated time for working on projects, enable fellows to engage in extensive PCOR seminars, and provide the opportunity for fellows to discuss their projects with mentors, colleagues, and faculty at Pitt.The total number of URB trainees in our programs as well as their percentage of the total trainee cohort indicate an encouraging trend toward better recruitment and retention of URB scientists. These aggregated numbers are summarized in CEED I and II combined have trained 76 URB scholars over the past 10 years, and with nine new trainees beginning in July, the programs are growing even stronger. Of our recently recruited cohort of TL1 scholars, 17% were from URBs. Of PROMISED participants, 39% were from underrepresented backgrounds. We have had 58 participants over two years, with 21 participating in the Career Coaching Workshop as well as the online modules. To date, we have trained 42 LEADS scholars across three cohorts. Having started LEADS with four MSIs as partners, we have since doubled that number and currently collaborate with eight MSIs. ENACT has trained 113 investigators in PCOR methods including Professors, Associate Professors, Assistant Professors, PhD Students, post-doctoral fellows, Master’s students, clinical research coordinators, and chief residents. In addition, 10 investigators, with a broad range of research interests, have graduated from the fellowship, and are now building a PCOR infrastructure at their home institution. Of this cohort of 113, 84% of trainees were from URBs.Studies examining additional outcomes, such as numbers of publications, grants, and academic jobs, are under way, and preliminary results are encouraging. For instance, 93% of the graduates of CEED I and II have been successful in obtaining grants as a Principal Investigator (PI) or Multiple-PI. Of those, eight (21%) have obtained career development awards and five have obtained research project grants (13%). These results provide strong evidence that CEED is meeting its goal.There have been efforts at other institutions to ensure that URB researchers within the pipeline flourish ,17,18. HIn keeping with the realization that successful efforts to diversify the workforce must address multiple barriers at once, the ICRE has developed programs that target workforce diversification from multiple angles and perspectives. To ensure that our approach is guided by the experiences and recommendations of URB scientists, we include our collaborators from MSI institutions at every opportunity. Our approach has enabled us to recruit and retain biomedical researchers from URBs at a rate favorable to increasing and maintaining the diversity of the biomedical workforce along the length of the career pipeline, from medical students to faculty.This short communication describes the rationale, design, and preliminary outcomes of six ICRE workforce diversification programs developed at one large Research I institution. As such, our approach and results may not be generalizable to institutions from other Carnegie Classifications. Additionally, our goal here is to provide a description of our process. Publications describing research methodology and reporting statistical significance are in preparation ,20. We are exploring ways to incorporate more opportunities for trainees from our geographically distributed partner institutions to meet in person to facilitate networking and relationship-building. We would also like to build more components such as near-peer mentoring, writing sprints, and grant writing groups to provide trainees with the structure and support they need to complete successful grant applications and manuscripts. Whether growing our programs or working to enhance the experience they provide, we are committed to offering unique training in clinical and translational research to trainees from diverse backgrounds, so that they may develop into successful clinical and translational researchers.


Antiretroviral therapy (ART) for HIV-infected persons and pre-exposure prophylaxis (PrEP) for uninfected persons are extraordinarily effective strategies for HIV prevention. In Africa, the region which shoulders the highest HIV burden, HIV care is principally delivered through public health HIV care clinics, offering an existing platform to incorporate PrEP delivery and maximize ART and PrEP synergies. However, successfully bringing this integrated approach to scale requires an implementation science evaluation in public health settings.The Partners Scale Up Project is a prospective, pragmatic implementation evaluation, designed as a stepped-wedge, cluster-randomized trial, operating at 24 clinics in Kenya. In collaboration with the Kenya Ministry of Health, we are catalyzing scaled implementation of PrEP delivery integrated in HIV care clinics. The intervention package includes staff training, clinic streamlined access to PrEP commodity from the Kenya Medical Supply Authority, and ongoing intensive technical assistance to rigorously assess how PrEP delivery is implemented. PrEP service delivery including retention efforts are conducted by the clinic staff with no additional resources from the project. Guided by the RE-AIM  framework and Consolidated Framework for Implementation Science Research, project progress and learning are documented through ongoing monitoring and process evaluations, including chart abstraction and individual and key informant interviews, to evaluate pragmatic rollout and understand barriers and facilitators for successful PrEP delivery in this setting. In this staged rollout design, each step provides data for both pre-implementation (baseline) and implementation periods, and we will compare time points across steps in the baseline versus implementation periods.Cost-effective delivery models are urgently needed to maximize the public health impact of PrEP and ART. The Partners Scale Up Project will set the stage for full-scale PrEP implementation fully run and owned by the Kenya Ministry of Health. The work combines nationally sponsored PrEP delivery with technical support and implementation science from academic partners, defining a new but sustainable paradigm for public health collaboration.NCT03052010.Registered with ClinicalTrials.gov on February 14, 2017: Heterosexual HIV-serodiscordant couples  are common in high HIV prevalence African settings , 2. HalfIn September 2015, the World Health Organization (WHO) recommended ART for all HIV-diagnosed persons and PrEP for persons at high risk of HIV acquisition . In the The Partners Demonstration Project  which shFacilitate delivery of PrEP integrated into ART care for HIV-serodiscordant couples at scale in public HIV care centers in Kenya and evaluate program impact;Assess facilitators and barriers to (a) implementation of PrEP within ART delivery settings and (b) optimized PrEP adherence in public health context with limited measurement capacity;Determine efficiency, cost, and cost-effectiveness of integrated PrEP and ART when delivered in public health clinics; andDevelop operational tools that will expand and support delivery of PrEP at scale and secure buy-in from relevant stakeholders to ensure delivery continues to scale up at the national level.The overall goal of the Partners Scale Up Project is to serve as a catalyst for expansion of PrEP delivery in public HIV clinics in Kenya and to document best practices for PrEP delivery. The specific aims are:The Partners Scale Up Project is a prospective, pragmatic implementation evaluation, designed as a stepped-wedge, cluster-randomized trial, operating at 24 clinics in Kenya. In this design, each step provides data for both pre-implementation (baseline) and implementation periods, and data analysis proceeds by comparing time points across steps in baseline versus implementation periods. In collaboration with the Kenya MOH, PrEP delivery was introduced in public health HIV clinics in a staged fashion, with ongoing intensive technical assistance and monitoring and evaluation conducted to rigorously assess how PrEP delivery is being implemented. PrEP provision including behavior risk assessment, demand creation, and retention activities are conducted by public health staff, with no additional resources provided by the project team. Project progress and learning are documented through ongoing monitoring and process evaluations, including chart abstraction and individual and key informant interviews, to evaluate pragmatic rollout and understand barriers and facilitators for successful PrEP delivery in this setting.HIV-uninfected individuals with HIV-positive sexual partners became eligible for PrEP per the Kenya national guidelines on use of antiretroviral drugs for treatment and prevention of HIV released in 2016 , with coThe Partners Scale Up Project is being implemented in 24 Comprehensive Care Clinics  in two geographical regions of Kenya: Central and Nairobi regions, herein referred to as Central  and Nyanza, herein referred to as Western . High-volume clinics with established ART programs were identified. Final participating clinics were then selected in consultation with MOH/National AIDS & STI Control Programme (NASCOP) and county health authorities prior to project initiation and reflect the Kenya Ministry of Health HIV priority areas based on HIV prevalence, diversity, and health care settings Fig. . LessonsBeginning February 2017, we implemented a stepped-wedge trial design to randomly assign 24 HIV care clinics to scaled implementation of PrEP integrated in HIV clinics for couples. During the project pre-implementation period, PrEP was sanctioned as part of  standard of care by the Kenya national guidelines but there were no systematic approaches in place for implementation in clinical settings. The project intervention is to be a catalytic force to integrate PrEP delivery in public HIV clinics nationally and the intervention package includes staff training, clinic streamlined access to PrEP commodity from Kenya Medical Supply Authority (KEMSA), and ongoing PrEP technical assistance. Prior to randomization, the 24 clinics were stratified by region , and each clinic was randomized to the order in which it would start implementing PrEP delivery. The randomization process was conducted at a public event attended by national and county health representatives. Facility leadership picked the order of initiation from an opaque bag containing numbered balls labeled from 1 to 12. Following randomization, the implementation was rolled out in groups of two to four clinics , the trial is estimated to have > 90% power to detect a minimum 10% difference in the number of at-risk HIV-uninfected individuals initiating PrEP (defined below as Reach) after implementing the intervention, with a two-sided alpha of 0.05. This difference was conservatively chosen, recognizing that as interventions move to scale their impact is often diminished . The form captures demographic information and ongoing evaluation for behavioral HIV risk factors, HIV testing and other laboratory monitoring, PrEP pharmacy dispensing, adherence self-rating, and side effects.Monitoring and evaluation and implementation process evaluation: The Partners Scale Up Project is conducting rigorous process evaluation activities to monitor how effectively PrEP delivery is implemented, including mixed-methods assessments to explore and gain deep understanding of the process of PrEP implementation and contextual influences on implementation and outcomes in clinical settings. Domains defined in the RE-AIM implementation science framework [ramework   and individual clinical records. Individual data is used to characterize PrEP initiation, HIV risk profiles of PrEP initiators, self-reported adherence, retention, HIV infection, and side effects.Adherence is essential for PrEP efficacy , 30. At 4.Economic evaluation: Estimating program impact and cost is necessary to inform public health decision-makers when deciding on HIV treatment and prevention policies and resource allocation. Time and motion studies to follow patients through each PrEP service delivery point are conducted to characterize service delivery models, including appropriate personnel, task shifting, and costs. Program cost for delivery, time spent to deliver PrEP, laboratory costs, and retention activities  are documented. We also estimate the financial and opportunity cost to PrEP recipients of transportation and time spent at the clinic in exit surveys and time and motion studies.5.Stakeholder engagement: The project conducts relevant stakeholder engagement activities to facilitate buy-in and ensure PrEP delivery continues to scale up at the national level. The project team is part of the Kenya national PrEP Technical Working Group  and uses this platform to offer guidance and technical support needed to deliver PrEP at scale on a national level. The project regularly conducts stakeholder meetings attended by representatives from the MOH, NASCOP, National AIDS Control Council, county government officials, other PrEP-implementing partners, clinic managers, and providers from all implementing clinics to review progress.Qualitative interviews are prospectively conducted to rigorously understand delivery, at the level of providers, organization , and users. Provider interviews with MOH staff at clinics  focus on operational delivery to understand acceptance, barriers, facilitators, and opportunities for efficiency. After each interview, short debriefing reports are used to identify emerging themes that affect implementation and those are quickly fed back to clinics prior to formal qualitative analysis. Patient interviews also focus on delivery , structural , individual , and dyadic  factors that may influence PrEP implementation and use. Additional complementary exit surveys with a subset of patients focus on user experiences and satisfaction.Key quantitative program implementation outcomes will include (a) Reach, defined as the number of at-risk persons initiating PrEP; (b) Effectiveness, defined as the number of HIV-uninfected on PrEP partners staying HIV-uninfected and adherence to PrEP as measured by tenofovir levels in DBS; and (c) Adoption, measured by PrEP continuation, number of serodiscordant couples newly identified through couples HIV testing. HIV risk profiles of PrEP initiators will be characterized using a validated risk score for HIV-serodiscordant couples , which wThe project uses multiple data sources Table  that wilAll abstracted health and patient data are handled in a secure and confidential way through adherence to institutional policies and procedures for securely storing, maintaining, and updating health record information. All health records and patient data are securely stored on password-protected and encrypted servers, and these data will not be released externally except under specific data-sharing agreements. All study results will be presented in aggregate, and no individual patient or provider will be identifiable.T tests will be used to detect differences in mean levels of continuous variables and chi-square tests for dichotomous variables.The primary outcome will be the number of at-risk persons initiated on PrEP (Reach). The number initiated on PrEP during baseline period  will be compared with that across the implementation observation periods (exposed or intervention period). Generalized linear mixed models, to estimate the primary intervention effect where both differences observed within steps (between randomized clinics) and changes observed within each clinic as it implements the intervention (within clusters), contribute information. A random effect for each clinic, a fixed effect for each time step, and the fixed intervention effect will be fitted for each time period. Categorical variables will be detailed in tables, and continuous measures will be summarized using means and standard deviations or medians and ranges, as appropriate. Qualitative data will be used to interpret and explain the results of the various individual RE-AIM dimensions or patterns of results across dimensions and clinics. We will use an inductive, content analysis approach to analyze the qualitative data  involving an iterative coding process and category construction using qualitative analysis software. The development and analysis of the qualitative research codebook will be guided by the domains and constructs defined in the CFIR , 32. TheWe will estimate total program cost and cost per person-month of PrEP use from data collected from project expense reports, time and motion observations, and commodity costs obtained from implementing partners. We will characterize efficiency as time per client served, time clients spend at the clinic, or cost per client on PrEP per year. Following WHO guidelines, we will estimate the incremental cost-effectiveness ratio of PrEP delivery integrated into public health HIV care clinics relative to current practice. We will use mathematical models to estimate health outcomes of integrated PrEP delivery beyond the scope of this project, parameterizing the models with PrEP use characteristics  observed in the Partners Scale up Project and prior results from studies of serodiscordant couples and the literature. Incremental cost-effectiveness ratios will evaluate the incremental cost per (1) HIV infection averted, (2) HIV-related death averted, and (3) HIV-related disability-adjusted life year (DALY) averted by integrated PrEP provision, accounting for both additional costs incurred by the PrEP program and HIV care and treatment costs averted. These analyses will help decision-makers define priorities and allocate resources.ClinicalTrials.gov on February 14, 2017 (NCT03052010). Amendments to the study protocol will require approval from the Scientific and Ethics Review Unit of the Kenya Medical Research Institute and the Human Subjects Division of the University of Washington. Any amendments will be communicated via trial registration updates and reported in any published manuscripts associated with the study as necessary.This protocol was registered with The study team for this award is committed to public dissemination of results of clinical trial to local stakeholders in Kenya, the global scientific community, and global policymakers. Dissemination of study results will follow principles of good participatory practice. Results will be published in conference abstracts and peer-reviewed journals. Study results will be disseminated through presentations to global and local stakeholders and policymakers in Kenya, including working in close collaboration with the Kenyan Ministry of Health to help foster immediate translational impact. Authorship eligibility will be determined according to the International Committee of Medical Journal Editors recommendations.The project was activated in February 2017 and implementation is currently ongoing and expected to end in 2021.In moving from clinical trial evidence to programmatic delivery of new interventions, implementation science evaluations can guide optimization and contextualization of the intervention. For novel HIV prevention interventions, like PrEP, the potential pathway for this transition to implementation has been defined as follows: clinical trials are followed by open label extensions, which provide first access to the product in the trial population, then demonstration projects that “road test” the intervention among individuals who had not been in the clinical trials and using strategies to mimic real-world delivery, and finally product introduction, which leads the intervention to scale through integration into existing health systems . We haveThe Partners Scale Up Project extends the vast experience in HIV prevention science and PrEP in Kenya to catalyze scaled implementation of PrEP delivery for couples in public health clinical settings. The hallmark of our approach is to set the stage for next steps for full-scale implementation with a sustainable PrEP program that is fully run and owned by the Kenya Ministry of Health. The work combines nationally sponsored PrEP delivery with technical support and implementation science from academic partners, defining a new but sustainable paradigm for public health collaboration. Examples of public health practice outputs from the project will include optimized clinic-level PrEP commodity management, development and dissemination of provider guidelines and delivery tools, and clinician technical support.Translating effective interventions to routine practice is challenging. Integrating rigorous assessment of implementation strategies aimed at optimizing uptake of novel interventions is critical for understanding why an intervention may work or not work and under what context. We have applied the RE-AIM , 35 and This project is using a stepped-wedge pragmatic study design to reconcile the constraints between programmatic implementation and need for rigorous scientific evaluations. The design is especially relevant for proven interventions that cannot ethically be withheld but which cannot realistically be moved to scale simultaneously, which is the situation with PrEP scale up in Kenya. Integrated PrEP and ART for couples is an ideal candidate for a stepped-wedge design across HIV treatment clinics, given its demonstrated effectiveness, opportunity to bring to scale, logistical feasibility of scaling and assessing delivery with each wave of implementation, and utility of scaling within a clinic .In summary, Kenya’s enabling policy environment for PrEP implementation permits a rigorous evaluation of national scale up of PrEP delivery for HIV-serodiscordant couples in public health settings. Findings from this work will inform how to effectively integrate PrEP in HIV clinics and how to efficiently roll out this strategy and achieve national impact.


The emergence of severe acute respiratory syndrome (SARS) underscored the importance of influenza detection and response in China. From 2004, the Chinese National Influenza Center (CNIC) and the United States Centers for Disease Control and Prevention (USCDC) initiated Cooperative Agreements to build capacity in influenza surveillance in China.From 2004 to 2014, CNIC and USCDC collaborated on the following activities: 1) developing human technical expertise in virology and epidemiology in China; 2) developing a comprehensive influenza surveillance system by enhancing influenza-like illness (ILI) reporting and virological characterization; 3) strengthening analysis, utilization and dissemination of surveillance data; and 4) improving early response to influenza viruses with pandemic potential.Since 2004, CNIC expanded its national influenza surveillance and response system which, as of 2014, included 408 laboratories and 554 sentinel hospitals. With support from USCDC, more than 2500 public health staff from China received virology and epidemiology training, enabling > 98% network laboratories to establish virus isolation and/or nucleic acid detection techniques. CNIC established viral drug resistance surveillance and platforms for gene sequencing, reverse genetics, serologic detection, and vaccine strains development. CNIC also built a bioinformatics platform to strengthen data analysis and utilization, publishing weekly on-line influenza surveillance reports in English and Chinese. The surveillance system collects 200,000–400,000 specimens and tests more than 20,000 influenza viruses annually, which provides valuable information for World Health Organization (WHO) influenza vaccine strain recommendations. In 2010, CNIC became the sixth WHO Collaborating Centre for Influenza. CNIC has strengthened virus and data sharing, and has provided training and reagents for other countries to improve global capacity for influenza control and prevention.The collaboration’s successes were built upon shared mission and values, emphasis on long-term capacity development and sustainability, and leadership commitment. The Chinese National Influenza Center of the Chinese Center for Disease Prevention and Control (China CDC) and the Influenza Division of the United States Centers for Disease Control and Prevention first discussed influenza virological surveillance in China in 1978. In 1989, CNIC and USCDC signed agreements that enabled USCDC to provide technical and financial support for influenza surveillance in China and laid the foundation for future collaborations between the two agencies. Initially, USCDC provided funds directly to CNIC for laboratory training and specimen sharing; later, funding was provided through WHO headquarters, and subsequently through the WHO Western Pacific Regional Office. Between 1989 and 2004, CNIC and USCDC staff traveled through WHO. Between 1989 and 2004, CNIC and USCDC staff traveled to each other’s agencies for training and collaborative studies.In 2000, China enhanced earlier influenza surveillance efforts by establishing an influenza-like illness (ILI) and virological surveillance system to report ILI cases and isolate viruses for seasonal influenza vaccine strain recommendations. The surveillance system, including 8 network laboratories and 31 sentinel hospitals, did not capture the diversity of influenza activity and viruses circulating throughout the country. In addition, China recognized that the poor quality of the data with respect to completeness, timeliness and accuracy, limited the system’s capacity to contribute to public health practice. The emergence of SARS in 2003 [In this report, we review the China-US laboratory collaboration on influenza from 2004 to 2014, to share best practices and lessons learned, and to assess how this collaboration builds capacity in the prevention and control of influenza in China and globally.Developing human technical expertise in virology and epidemiology in ChinaBuilding upon existing technical exchanges and training programs, CNIC and the Influenza Division of the USCDC signed a bilateral Cooperative Agreement in 2004 to develop and build the capacity of the influenza surveillance laboratory networks in China. In 2007, China CDC and USCDC signed an additional Cooperative Agreement on emerging and remerging infectious diseases which was funded by the USCDC GDD program that allowed for enhanced collaborations with CNIC in the field of influenza. The objectives for these collaborations were: 1) to improve and expand the influenza surveillance system in China; and 2) to build capacity for early detection and response to seasonal influenza, avian influenza and other influenza viruses with pandemic potential. In September 2007, the USCDC deployed the first influenza assignee to China and established a USCDC program team in China, comprised of both a USCDC staff member from the United States and one to three locally-employed staff, to ensure effective communication and cooperation between CNIC and USCDC. Members of the USCDC team in country and colleagues from the Influenza Division in Atlanta worked closely with CNIC on a routine basis and contributed to numerous accomplishments including: 1) developing human technical expertise in virology and epidemiology in China; 2) improving the quality and function of the influenza surveillance system in China; 3) strengthening the analysis, utilization and dissemination of surveillance data; and 4) improving early response to avian influenza and other influenza viruses with pandemic potential. The following collaborative activities were identified to meet these priorities: 1) training and enhancing human workforce development in CNIC and network laboratories across the country; 2) strengthening quality improvement activities including a) improving the quality of influenza virological surveillance through nucleic acid detection, virus isolation in embryonated eggs, genetic and antigenic characterization, and receptor-binding specificity characterization; b) strengthening quality assurance of network laboratories by conducting annual laboratory quality assessments; c) initiating the ISO15189 accreditation program; and d) introducing new technology including Nucleic Acid Sequence Based Amplification (NASBA), multi-plex PCR, and deep sequencing in CNIC; 3) adding new functions to the influenza surveillance system including: drug resistance surveillance; monitoring serologic status among occupationally exposed groups; conducting environmental sampling surveillance; and using multi-pathogen detection platforms for the surveillance of other respiratory viruses; 4) establishing an influenza information system to integrate epidemiology and laboratory data and to promote timely data analysis and sharing; and 5) promoting international collaborations in the form of information exchanges and virus-sharing during the 2009 influenza pandemic and the influenza A(H7N9) outbreaks.2.Improving the quality and function of the influenza surveillance system in ChinaFrom 2004 to 2014, 15 CNIC staff received training in CDC Atlanta, from one month to 1.5 years in length, on topics including influenza surveillance and laboratory management, reverse genetic techniques, serological techniques, pathology, antigenicity characterization, and drug resistance surveillance. CNIC provided lecture-based training to 2320 staff from network laboratories and sentinel hospitals, and hands-on training to 450 lab specialists on cell culture, virus isolation, and serology testing and gene sequence analysis with USCDC support.During this timeframe, China also expanded its ILI and virological surveillance network. In 2005, the network increased from 8 to 63 network laboratories and 31 to 197 sentinel hospitals, primarily supported with funds from the Chinese government, with supplemental project-based financial support from USCDC and WHO. During the 2009 influenza A(H1N1) pandemic period, the Chinese government expanded the network further to include 411 laboratories and 556 sentinel hospitals  for Reference and Research on Influenza. CNIC implemented performance improvement measures based on WHO requirements, and launched a one-year assessment in November 2008. In October 2010, CNIC was officially designated as the world’s sixth WHO CC for Influenza, joining laboratories in Australia, Japan, the United Kingdom and the United States.3.Strengthening the analysis and dissemination of surveillance dataAs the ILI surveillance system expanded in size and capacity, its function also expanded to the early detection of emerging novel influenza viruses. Built on the existing influenza surveillance network, CNIC developed an influenza identification platform which can detect all types/subtypes of influenza viruses including zoonotic infections. This system allowed CNIC to confirm China’s first human infections from A (H7N9), A (H10N8) and A (H5N6) viruses just 1–3 days after receiving specimens –14.3.StrCNIC developed an information system with three online components: the Influenza Surveillance Information System, the Infectious Disease Surveillance Platform and the Influenza Prediction and Early Warning Platform. Local CDC users across China can access this system to: 1) report cases of ILI, pneumonia of unknown etiology, and severe acute respiratory infection (SARI); and 2) upload laboratory testing results. The Infectious Disease Surveillance Platform also collects test results from environmental surveillance and serologic studies of groups with occupational exposure to poultry. With support from the collaboration with USCDC strengthened data analysis and, since 2009, has generated online Weekly Influenza Reports to share when, where and which influenza viruses are circulating in China. The weekly reports, in both Chinese and English, are emailed to key stakeholders and are also made available on the CNIC website .The New England Journal of Medicine 11 days after case confirmation [4.Improving early response to novel influenza viruses with pandemic potentialSince 2005, CNIC also has reported influenza surveillance data to WHO FluNet . During irmation . Subsequirmation –30 for tDuring the early stages of the 2009 H1N1 pandemic, USCDC and China CDC established routine conference calls between directors and experts of the two centers. USCDC shared the genetic sequence of the pandemic virus with CNIC, allowing CNIC to rapidly develop nucleic acid detection kits which were transported to national influenza network laboratories and other laboratories across the country. The availability of testing reagents ensured accurate estimates of the magnitude of the pandemic in China and allowed the Chinese government to coordinate an appropriate response. In addition, the USCDC country team in Beijing worked closely with China CDC experts on pandemic risk assessment and response.5.Promoting international collaboration and cooperationIn 2013, CNIC shared novel avian influenza A (H7N9) viruses from human infections with WHO Collaborating Centers and other qualified laboratories worldwide. CNIC also worked with WHO, USCDC and other international laboratories to modify serological protocols for influenza A (H7N9) virus detection . InternaAs a new WHO Collaborating Centre for Influenza, CNIC not only increased influenza control and prevention capacity throughout China, but also throughout the region. In recent years, CNIC, with Chinese government support, has provided hands-on laboratory training to neighboring countries, such as from the Association of Southeast Asian Nations (ASEAN). More specifically: in 2007, CNIC provided avian influenza laboratory diagnostic training to 18 trainees from 9 ASEAN countries; during the 2009 pandemic, CNIC provided free test kits to 13 countries and training on biosafety and laboratory diagnosis of A(H1N1pdm09) virus for 16 participants from 8 ASEAN countries; and in 2013, CNIC conducted training on serological detection of avian influenza A(H7N9) virus for 7 participants from Indonesia, Laos, Malaysia, Mongolia, Philippines, Thailand and Vietnam. Further, CNIC shared serological and nucleic acid testing protocols with WHO and provided diagnostic kits for pandemic H1N1 2009 to Brunei, Cambodia, Cuba, Indonesia, Laos, Malaysia, Mongolia, Papua New Guinea, Philippines, Singapore, Thailand and Vietnam, and seasonal influenza surveillance-related reagents and consumables to DPR Korea.In the last decade, the CNIC-USCDC collaboration has built capacity in seasonal and novel influenza prevention and control in China and beyond. The workforce of the influenza surveillance network, both within CNIC and within network laboratories and sentinel hospitals throughout China, is now well developed. The influenza surveillance system expanded in size, capacity, and function, and improved the quality of its testing and use of data. No longer focused on seasonal influenza alone, the ILI surveillance network detected the first human infections with influenza A (H7N9) virus, A (H10N8) virus, A (H5N6) virus and other novel avian influenza viruses. The collaboration promoted timely data analysis and sharing, including the development of an on-line influenza weekly report for early case reporting and information sharing. In addition, the collaboration enabled CNIC to provide technical assistance in the field of influenza laboratory diagnostics to numerous countries in the region. One challenge faced by the CNIC-USCDC collaboration during the past decade was the limited effective coordination with animal health sectors in the field of avian influenza in China. In the future, the two agencies plan to strengthen avian influenza collaborations within a one-health approach that promotes a multi-sectoral response to emerging influenza threats. A major contributor to the success of this collaboration was that it complemented the existing national influenza program, in addition to the Chinese government’s commitment to developing an extensive and robust influenza surveillance system. In 2009, the Chinese government invested the equivalent of 46 million US dollars to expand the network. All collaborative efforts were designed to support the successful expansion of the network. For example, to ensure the quality of the new system, the CNIC-USCDC collaboration provided training for laboratory specialists within the new network laboratories and sentinel hospitals and improved quality assessment of the system. The collaboration also supported the establishment of new components of the surveillance system, such as antiviral resistance surveillance and environmental surveillance. At the outset, CNIC and USCDC agreed that these new components would soon be fully incorporated and maintained by the national program. In this way, the collaboration maximized existing government investments in influenza surveillance. Further, the collaboration demonstrated the importance of influenza surveillance during response efforts to the 2009 pandemic and the 2013 A(H7N9) outbreak, ensuring continued government commitment to the influenza surveillance system in the future.The CNIC-USCDC collaboration was strengthened by the two agencies’ shared mission and values. Long before the launch of the official cooperative agreement in 2004, both agencies recognized the importance of improving influenza surveillance in China; the recent A(H5N1) and SARS outbreaks highlighted China as a potential source for emerging novel respiratory viruses with pandemic potential. Further, USCDC’s strategic priorities at the time included increasing global surveillance and response capacity to strengthen global health security and China, the most populous country in the world, played a critical role. In this way, the collaboration between CNIC and USCDC was founded on a joint mission and mutual, well-defined priorities.Another factor contributing to the success of the collaboration was its commitment to capacity building. CNIC plays a key role managing and developing the influenza surveillance network in China, and therefore, CNIC staff members who received training at USCDC and other international organizations played a vital role during the responses to both the 2009 A(H1N1) pandemic and the 2013–2014 A(H7N9) outbreaks in terms of early virus identification, deep gene sequencing, vaccine development, and serving as trainers in both domestic and international settings.Finally, this CNIC-USCDC collaboration would not have thrived without the shared vision and commitment of the leaders within the two agencies. Fortunately, the formal Cooperative Agreement was built upon the foundation of a long-term collaboration between CNIC and USCDC. In the decades prior to 2004, influenza experts from both agencies had developed strong professional respect for one another, as they shared a profound interest and commitment to preventing and controlling influenza illness around the globe. The leadership’s respect and trust for one another likely facilitated the rapid joint responses to emergencies, which included data and virus sharing, technical exchanges, and joint manuscripts in the peer-reviewed literature.In the past decade, China rapidly expanded its capacity to detect and respond to seasonal influenza and novel influenza viruses with pandemic potential. The 2004–2014 China-US collaboration in the field of influenza demonstrates how two public health agencies worked together to expand a disease surveillance system, and ultimately improved the prevention and control of both seasonal and novel influenza viruses in China and the world.


Background: Non-binary and genderqueer (NBGQ) people are those who do not identify within the gender binary system , not falling exclusively in man/male or woman/female normative categories. A higher proportion of NBGQ people is usually found within young persons. This population is marginalized and, as such, is at risk of stigmatization and of developing negative health outcomes. As literature on the health of NBGQ people is sparse, this study aims at systematically review the limited studies on this field.Methods: The research questions which guided the systematic review were: (1) What are the differences in the health levels between NBGQ and binary transgender (BT) individuals? (2) What are the differences in the health levels between NBGQ and cisgender individuals? (3) Which medical and psychological interventions are most suitable for improving NBGQ health? According to PRISMA guidelines, a systematic search was conducted in PubMed, PsycInfo, Web of Science, and Google Scholar.Results: Eleven studies met the inclusion criteria for the current systematic review. Among them, 9 were focused on the health differences between NBGQ and BT individuals, 4 of the latter and 1 individually were focused on the health differences between NBGQ and cisgender individuals, and 1 was focused on the evaluation of health outcomes related to medical procedures. No studies assessed psychological interventions aimed at improving health in NBGQ individuals. All studies were cross-sectional, did not generally recruit a large sample of NBGQ individuals, and used non-probability sample design. Results related to the difference in health between NBGQ and BT were mixed; indeed, some found a better health status while others a worse one. Results related to the differences in health between NBGQ and cisgender highlighted higher health needs in NBGQ than in BT individuals. The only study analyzing the effects of medical interventions on health found that NBGQ female-assigned at birth individuals improved their quality of life after chest surgery.Conclusions: Although scholars are starting to pay attention to the NBGQ health, research needs to be expanded both in terms of methodology and research contents. Clinical, health-related social policies, and research recommendations in this field are reported. Transgender is an umbrella term referring to individuals who have a gender that differs from that normatively expected of their assigned sex [American Psychological Association (APA), non-binary and genderqueer (NBGQ) refers to individuals who have a gender identity that does not fall exclusively in man/male or woman/female normative categories. NBGQ individuals identify themselves with a neither exclusively masculine nor feminine gender, and their gender identity is situated beyond the gender binary, fluctuates between genders, or rejects the gender binary  of 14.320 transgender respondents identified themselves as NBGQ  What are the differences in the health levels between NBGQ and BT individuals? (2) What are the differences in the health levels between NBGQ and cisgender individuals? (3) Which medical and psychological interventions are most suitable for improving health in NBGQ population?A systematic review was performed to identify published papers on the health of NBGQ individuals using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines , qualitative studies, mixed-method studies, and longitudinal studies were considered eligible. Reviews, meta-analyses, letters to the editor, books or book chapters, commentaries, and abstracts were excluded.Two reviewers (CS and FM) extracted the relevant data and assessed titles and abstracts identified in the literature search. They also excluded duplicates from the dataset. Disagreements between the two reviewers were solved through the involvement of two additional reviewers (PV and RV). All studies which matched the inclusion criteria were reviewed by the authors (CS and FM) and any disagreement was settled through a discussion involving two other reviewers (PV and RV).n = 1); 2) no research designs were performed (n = 4); (3) the article did not specifically address health outcomes (n = 11); (4) the journal was not peer-reviewed (n = 1), and (5) the identity of participants was not clearly defined  (n = 2).The initial search identified 218 records, as shown in the PRISMA flow diagram . Only 2 The 11 papers included in the current systematic review are listed in N = 7), while 2 were conducted in UK, 1 in Spain, and 1 in Canada. Among the studies selected, 9 (81.81%) were focused on the health differences between NBGQ and BT individuals (first research domain), 4 of the latter and 1 individually (45.45%) were focused on the health differences between NBGQ and cisgender individuals (second research domain), while only 1 (9.09%) was focused on the evaluation of health outcomes related to medical procedures . No studies assessed psychological interventions aimed at improving health in NBGQ individuals.Overall, studies were published between 2016 and 2019 and all of them used a cross-sectional design with quantitative methods, except for one study which supported quantitative data with focus groups. Considering the number of NBGQ individuals within the general sample recruited, the NBGQ subsample size was not generally large, as it ranged from 28 to 380 participants. However, considering the cross-sectional nature of the studies, some of them seem to have acceptable subsample size  were NBGQ, all FAAB. Among them, 56% (N = 33) completed the post-operative questionnaire. NBGQ participants agreed that surgery improved their quality of life, comfort with exercise, sex life, and comfort in physical appearance with and without clothes. Thus, this study shows the benefits that also NBGQ individuals might experience from undergoing medical procedures. As reported before, no studies addressing specific psychological interventions  for the improvement of health in NBGQ individuals were found.Only one study addressing health outcomes related to medical interventions for NBGQ individuals was found. Among 458 patients undergoing gender-affirming chest surgery, Esmonde et al.  found thThe aim of this study was to systematically review the literature related to the health of NBGQ individuals, exploring in particular 3 domains: (1) difference in health between NBGQ and BT individuals; (2) difference in health between NBGQ and cisgender individuals; and (3) medical and psychological interventions addressed to the improvement of NBGQ health. A total of 11 studies met the inclusion criteria and were used for this systematic review.As regards the characteristics of the selected studies, papers were recently published (from 2016), prevalently used a cross-sectional design with quantitative methods, did not generally recruited large NBGQ subsample . This is particularly noteworthy as it seems that NBGQ individuals analyzed in the studies selected, except for the NBGQ subsample recruited by Jones et al.  whose meAs regards the differences in health between NBGQ and BT individuals , studies selected reported mixed findings, some finding a better health status  are quite clearer than the previous ones. Indeed, although Warren et al.  did not Finally, the only study analyzing the effects of medical interventions on health of NBGQ individuals  found that NBGQ FAAB individuals, contrary to the belief that they would not need to medically affirm their gender, improved their quality of life and health after chest surgery , From a health-related social policy perspective, our findings shed light on the urgency of implementing policies to address health needs of NBGQ people, overcoming discriminatory practices and promoting health equity. First, NBGQ identities should be recognized by healthcare service systems and providers as existing and healthy identities. To this end, healthcare providers could benefit from specialized training aimed at improving the knowledge on NBGQ identities, as well as the related specific health needs  NBGQ identity development and specific challenges, matching theoretical perspectives on gender diverse population  with theoretical frameworks of developmental psychology ; (b) causal relationships between stigmatizing processes , protective factors  and health outcomes across different life stages;To expand studies to geographical contexts different from USA, UK, Canada, and Spain, as well as to deepen the role of socio-economic status in health disparities in order to build culturally competent studies on NBGQ population;To make every effort to recruit probability samples to allow generalization of the results to the specific population from which the sample was recruited. Although recruiting probability sample in LGBT community is a challenging task ;To build randomized controlled trial experiments to assess the efficacy of specific psychological interventions  in improving health in NBGQ people.This systematic review shows that the scientific interest on NBGQ health is growing but, at the same time, needs to be expanded both in terms of methodology and research contents. Indeed, it was hard to obtain a clear picture of the NBGQ population in terms of health, as all selected studies used a cross-sectional design and reported data on non-probabilistic samples. Notwithstanding these limitations, studies provided valuable information on the health of NBGQ people, starting to run an innovative research field which unhooks transgender population from a gender binary system that is often reproduced in scientific research. Thus, this review may represent one of the references for future studies, which could hopefully follow the research recommendations to increase the knowledge on NBGQ health building an increasingly relevant research from both the cultural and methodological point of view, as well as informing affirmative clinical practice and social policies to reduce the health equity gap.CS, FM, and RV conceived and designed the study and drafted the manuscript. CS and FM managed the literature searches and analyses. NM, MB, and VB refined the literature search. PV and RV solved disagreements between two main reviewers (CS and FM). All authors revised the article critically and read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Instagram is increasingly becoming a platform on which visual communication of cancer takes place, but few studies have investigated the content and effects. In particular, a paucity of research has evaluated the effects of visual communication of cancer on participative engagement outcomes.The objective of our study was to investigate cancer-related beliefs and emotions shared on Instagram and to examine their effects on participative engagement outcomes including likes, comments, and social support.This study analyzed the content of 441 posts of #melanomasucks on Instagram and assessed the effects of the content characteristics on outcomes, including the number of likes and comments and types of social support using group least absolute shrinkage and selection operator logistic regression.P<.001) and social support comments (P=.048). Posts about physical consequences of melanoma decreased likes (P=.02) but increased comments (P<.001) and emotional social support (P<.001); posts about melanoma treatment experience increased comments (P=.03) and emotional social support (P<.001). None of the expressions of positive emotions increased likes, comments, or social support. Expression of anger increased the number of likes (P<.001) but those about fear (P<.001) and joy (P=.006) decreased the number of likes. Posts about fear (P=.003) and sadness (P=.003) increased emotional social support. Posts showing images of melanoma or its treatment on the face or body parts made up 21.8% (96/441) of total posts. Inclusion of images increased the number of comments (P=.001).Posts about controlling melanoma were most frequent , followed by 240 (54.4%) posts about outcomes of having melanoma. Ninety posts (20.4%) were about the causes of melanoma. A greater number of posts expressed positive  than negative emotions . Eighty posts (18.1%) expressed hope, making it the most frequently expressed emotion; 49 posts expressed fear (11.1%), 46 were humorous (10.4%), and 46 showed sadness (10.4%). Posts about self behavior as a cause of melanoma decreased likes (To our knowledge, this is the first investigation of the content and effects of user-generated visual cancer communication on social media. The findings show where the self-expressive and social engagement functions of #melanomasucks converge and diverge, providing implications for extending research on the commonsense model of illness and for developing conceptual frameworks explaining participative engagement on social media. Instagram is rapidly becoming a public platform where images, beliefs, and emotions about cancer are expressed and shared. At the time of this writing, there are millions of Instagram posts about various cancer experiences. One of the fastest growing platforms of social media, following only Facebook , InstagrDespite this popularity, visual communication of cancer on social media remains underinvestigated. Extant research on social media content related to cancer has focused on text-based content, such as that on Twitter ,6. Only Melanoma is the fifth most prevalent cause of cancer death affecting both men and women in the United States . ResearcBased on the premise that beliefs and emotions about cancer underpin the visual images posted on Instagram, this study used the commonsense model of illness representation -15 as anAlong with beliefs, emotions are an important part of illness experiences -17. MartUnder this overarching framework, this study used the cognitive appraisal theory of emotions ,20 to anBy investigating Instagram posts about cancer beliefs and emotions, we seek to add new insight to extant research on the commonsense model of illness. Prior research on illness perceptions has used responses prompted by survey or interview questions . On InstIn addition, we will investigate the visual images particular to the communication of melanoma. These would include images of melanoma or its treatment. Patients’ visual documentation of melanoma or its treatment may hold special meaning to them. Furthermore, these images may increase other users’ engagement in cancer communication on social media in forms such as comments. Our first set of research questions concerned self-expressed beliefs and emotions about melanoma on Instagram:Self-expression of illness beliefs and emotions on social media invites participative social engagement. It is important to investigate the dynamics between Instagram posts about cancer and the extent and types of network engagement that they generate. This line of research can help shift gears from the current emphasis on the content of social media communication to an expanded research focus that can illuminate the relationship between content characteristics and the participative engagement that they generate.To investigate the effects of visual expressions of cancer, we focused on participative engagement, as indicated by the number of likes and comments and the types of social support provided in the comments. As an affective reaction, likes may be the most basic form of participative engagement in social media interactions . CommentIn addition to likes and comments, the provision of social support may be another form of participative engagement on Instagram. Individuals with chronic illnesses increasingly use social media to connect with others and to seek and provide support ,36. AlthExtant literature suggests there are four primary types of social support. They are as follows: esteem, emotional, informational, and instrumental ,40. EsteThe universe from which we draw the sample for this study was #melanomasucks. As discussed above, people use hashtags to label their posts and to ensure the visibility, searchability, and documentability of their posts . We randConsistent with the sampling protocol for social media content analyses offered by Kim, Huang, and Emery , we asseTwo coders were extensively trained and they worked together to establish intercoder reliability. We used 10% of the sample to assess the intercoder reliability of each variable. Krippendorff alpha  ranged fFor cancer beliefs, we assessed the presence (1) and absence (0) of beliefs about causes, consequences, and control of melanoma. Under causes, we analyzed the presence or absence of beliefs related to hereditary factors, self behavior, system or institution, natural environment, social environment, built environment, or chance. Under outcomes, we examined the presence or absence of expressions of negative physical, cognitive, emotional, and relational consequences of having melanoma; we also coded for the presence or absence of expressions of positive aspects of having melanoma. Under control, we investigated beliefs related to self and collective actions pertaining to the prevention and control of melanoma. Individuals’ actions included primary prevention , secondary prevention (screening), and treatment; societal actions included raising awareness, fundraising, more research, greater funding allocation, and policy change.For cancer emotions, we assessed the presence or absence of three negative emotions of fear, anger, and sadness and three positive emotions of hope, joy, and humor. Fear was a depiction of danger or threat; anger was a depiction of wrongful offense; and sadness was a representation of irrevocable loss. Hope was operationalized as a positive emotional state involving goals or planning to meet goals ; humor was a depiction of an effort make fun of or ease a difficult situation; and joy was a variant of happiness that indicated progress toward a goal.For research questions 1 and 2, which concerned the characteristics of the content, we computed the frequency and percent distribution of the variables. For research questions 3 and 4, which concerned melanoma beliefs and emotions influencing the number of likes and comments, we used negative binomial regressions. In each model, the number of likes or comments was regressed onto cancer beliefs and emotions. The log number of followers were adjusted as an offset in the regression model. To examine research question 5, predictors of the types of social support, we used a multivariate logistic regression model for each support type. We did not employ multinomial regression to reflect that the social support types were not mutually exclusive. Instead, we used separate binary logistic regression models for each of the four types of social support. In addition to these separate logistic regression models, we used a joint model using group least absolute shrinkage and selection operator (LASSO) logistic regression. To select variables that predict all types of social support, we penalized the total log-likelihood of four logistic regressions for all of the types of support by a group LASSO penalty that encourages the coefficients of a predictor to be zero for all types of support. This helped us select the same set of predictors for all types of support. To determine the penalty-tuning parameter, we selected the group LASSO models with the smallest Bayes information criterion. The number of followers was adjusted in both the separate and group LASSO models.Research question 1 asked what cancer illness beliefs are expressed in #melanomasucks. Beliefs about controlling melanoma were most frequently expressed , followed by beliefs about outcomes of melanoma , which in turn were followed by beliefs about the causes of melanoma . Of beliefs about controlling melanoma, awareness raising was most frequently expressed , followed by treatment , primary prevention , secondary prevention , and fundraising . Of beliefs about outcomes of cancer, physical consequences were the most frequently expressed , followed by emotional outcomes , relational outcomes , and equal representations of financial consequences  and positive outcomes . Of beliefs about causes of melanoma, self behavior was the most frequently expressed , followed by natural environment . A social environment that supports tanning behavior was expressed in 7.8% (7/90) of the posts.Research question 2 asked what emotions are expressed using #melanomasucks. Hope was the most frequently expressed emotion, such as by providing insight about or expressing trust in a treatment procedure , followed by fear, such as worry about the recurrence of melanoma . These were followed by equal representations of humor, such as making light of treatment results, ; sadness, such as remembrance of people who have died from melanoma ;and joy, such as patients expressing enthusiasm and gratitude during treatment . Anger was a rarely expressed emotion . Overall, there was a greater number of positive than negative emotional expressions 36.1% (159/441) vs 22.7% (100/441). Research question 3 asked whether images of melanoma or its treatment are included in #melanomasucks posts. In total, 21.8% (96/441) of the posts included images of melanoma or its treatment on the face or body parts. Posts showing images of melanoma on the face or body parts were about 4.3% (19/441) of the total posts. Post showing images of melanoma treatment on the face or body parts were about 17.5% of the total posts (77/441).P<.001). Expressions about physical (P=.03), financial (P<.001), and other negative consequences (P=.02) significantly decreased the number of likes. In contrast, expressions of positive outcomes of having melanoma significantly increased the number of likes (P<.001). Of control beliefs, posts about treatment (P=.02), fundraising (P=.008), and more research funding allocation (P=.008) decreased the number of likes. The effects of emotions on likes are presented in P<.001), whereas expressions of joy (P=.006) and fear (P<.001) decreased the number of likes.Research question 4 asked what beliefs and emotions expressed in #melanomasucks impacted the number of likes. The effects of beliefs on likes are presented in P<.001), whereas beliefs about financial consequences of melanoma decreased the number of comments (P<.001). Of control beliefs, those about treatment increased the number of comments (P=.03), whereas those about fundraising (P=.02) decreased the number of comments. None of the expressions of emotions were associated with the number of comments. Research question 6 asked whether images of melanoma or its treatment increased the number of comments. A significant positive association between such images and the number of comments was found . Inclusion of melanoma images in posts increased the number of comments.Research question 5 asked what beliefs and emotions expressed in #melanomasucks impacted the number of comments. As shown in Research question 7 asked what beliefs and emotions predicted what type of social support. To address this question, we first investigated whether beliefs and emotions predicted the presence or absence of social support using the entire dataset. Next, using only the cases that received social support, we examined predictors of specific kinds of social support.P=.048). Of outcome beliefs, those about physical consequences of having melanoma significantly increased social support comments  and those about relational consequences showed a marginally significant positive effect on social support comments . Of control beliefs, those about treatment increased social support comments . None of the emotions were significantly associated with social support comments.Of cause beliefs, that self behavior is responsible for melanoma significantly decreased social support comments  but increased emotional support ; similarly, emotional consequences decreased esteem support  but increased emotional support . Of control beliefs, those about treatment and fundraising were significant predictors per LASSO, which were confirmed in separate regression models. Expressions about treatment decreased esteem support  but increased emotional support ; beliefs about fundraising increased esteem support  but showed a marginally significant negative association with emotional support . Of emotions, fear and sadness were selected per LASSO. Fear decreased esteem support  but increased emotional support ; similarly, sadness decreased esteem support  but increased emotional support . No significant associations between the predictors of beliefs and emotions and the informational and instrumental social support types were found.None of the cause beliefs were significantly associated with the types of social support per LASSO. This was confirmed in separate regression models in which no significant association was found in any of the four models for the types of support. Of outcome beliefs, those about physical and emotional consequences were significant per LASSO and confirmed in separate regression models. Beliefs about physical consequences decreased esteem support . Of the cause beliefs, self behavior was the most frequently expressed, followed by natural and social environments.Convergence between self-expressed and socially engaged beliefs about melanoma was observed where frequent posts increased engagement from other users, for example, posts about melanoma treatment were frequent and they significantly increased comments and emotional social support. Likewise, expressions of the physical consequences of having melanoma were frequent and they increased comments and emotional social support. In addition, expressions of relational consequences of having melanoma were marginally linked to increased emotional social support.Divergence between self-expressive and social engagement functions of #melanomasucks was observed where frequent posts did not foster engagement from other users; for example, whereas self behavior as a cause of melanoma comprised 80% of cause-related beliefs, expressions of this belief decreased the number of likes and social support comments. Similarly, none of the cause beliefs were significantly associated with the number of comments. In addition, posts about financial consequences of having melanoma decreased the number of likes and comments. Although posts about personal experiences  engaged users with increased comments and emotional social support, posts that were less personal  decreased the number of comments.Intriguing patterns of results were obtained for the research questions concerning emotions. Regarding self-expression of emotions, users of #melanomasucks were more interested in expressing positive emotions  than negative emotions  and of the six emotions, hope was the most frequently expressed. These findings point to the need for more research on the roles of positive emotions and positive emotional expressions in cancer management.A notable contrast between positive and negative emotions emerged in relation to the self-expressive and social engagement functions. Positive emotions appear to serve more self-expressive functions than social engagement functions because they did not increase likes, comments, or social support. Although hope was the most frequently expressed emotion, it did not increase any of the indicators of engagement including likes, comments, or social support. Likewise, humor, which was apparently expressed in users’ efforts to make light of difficult melanoma-related situations, was not associated with the number of likes or comments. Moreover, expressions of joy decreased the number of likes. Somewhat similarly, posts that described positive aspects of cancer experiences increased the number of likes but not comments or social support. In comparison, although negative emotions were less frequently expressed, they enjoyed more social engagement from other users than positive emotions; for example, anger, which was the least frequently expressed emotion, significantly increased the number of likes. Although fear decreased the number of likes, it received emotional social support; expressions of sadness were unassociated with likes but they increased emotional social support.The results provide important implications for theory and research on the commonsense model of illness and participative engagement on social media. Extant research on illness perceptions using the commonsense model has employed a validated and standardized protocol  though iThe convergence and divergence of the self-expression and social engagement functions of #melanomasucks found in this study may point to an important new direction for future research on participative engagement on social media. The pattern of convergence and divergence that emerged appears to depart from the normative expectations in face-to-face interactions; for example, posts about financial consequences of having melanoma decreased the number of likes and comments. Similarly, expressions of positive emotions received little social engagement. These results add to the growing body of research examining the differences between online and offline communication behavior .Also noteworthy is the divergence between self-expressions of positive emotions and social support received. Arguing that emotions are socially interdependent by nature and elicit social sharing, Rime’  posited As the first investigation of visual cancer communication on social media, this study was limited to one cancer, melanoma, and one hashtag, #melaonomasucks. Building on this study, future research should examine whether the patterns of content and effects identified in this study are similar for other cancers and other cancer hashtags, where the similarities and differences arise in the expression of causes, outcomes, control, and emotions, and the participative engagement that these expressions may elicit. Using the framework developed in this study, future studies could employ a larger sample.This study provides an important first look at the content and effects of visual cancer communication on social media and a conceptual basis that future investigation of visual communication of other cancers can utilize. The convergence and divergence identified between self-expressions of cancer beliefs and emotions and the social participative engagement they foster offer new insight and directions for extending the research on cancer illness perceptions and for developing conceptual frameworks for explaining and predicting participative engagement in cancer communication on social media.


Optimal nitrogen (N) management is essential for profitable vegetable crop production and to minimize N losses to the environment that are a consequence of an excessive N supply. Proximal optical sensors placed in contact with or close to the crop can provide a rapid assessment of a crop N status. Three types of proximal optical sensors  for monitoring the crop N status of vegetable crops are reviewed, addressing practical caveats and sampling considerations and evaluating the practical use of these sensors for crop N management. Research over recent decades has shown strong relationships between optical sensor measurements, and different measures of crop N status and of yield of vegetable species. However, the availability of both: (a) Sufficiency values to assess crop N status and (b) algorithms to translate sensor measurements into N fertilizer recommendations are limited for vegetable crops. Optical sensors have potential for N management of vegetable crops. However, research should go beyond merely diagnosing crop N status. Research should now focus on the determination of practical fertilization recommendations. It is envisaged that the increasing environmental and societal pressure on sustainable crop N management will stimulate progress in this area. Generalr bodies ,6. Increh issues  and eutrosystems ,9,10,11.The protection of the environment has become a necessary consideration for intensive agriculture and horticulture. Nitrogen fertilizer management based on insuring production by using appreciable excessive amounts is no longer acceptable to modern societies ,13. The For optimal crop N management that ensures high production, while minimizing N losses to the environment, N fertilizer should be applied to match crop demand and to take into account N supplied by other sources, such as soil mineral N present at planting, and N mineralized from soil organic N, manure, and crop residues ,16,17,18A promising approach for the rapid and periodic assessment of crop N is the use of proximal optical sensors . They co3− leaching [This manuscript reviews the use of different proximal optical sensors for assessing crop N status and for N management of vegetable crops. To date, most of the evaluations of proximal optical sensors for crop N management have been with cereals for single side-dress N fertilizer applications at a given crop development stage or age. There have been a number of publications on the use and applicability of optical sensors for N management of vegetable crops; however, this information is dispersed, involving different crops and different sensors, and has never been thoroughly reviewed. Vegetable production has an inherently high nutrient pollution potential because of the intensive management and high value of the produce . The higleaching ,35,36.The three types of N-sensitive proximal optical sensors, suitable for crop N management applications, that have been most used with vegetable crops are reviewed here: Chlorophyll meters, reflectance sensors, and fluorescence-based flavonols meters . For eacThe first group of optical sensors studied for crop N management was chlorophyll meters, which indirectly estimate the relative chlorophyll content per unit of a leaf surface area . ChloropMost chlorophyll meters estimate the relative leaf chlorophyll content by measuring the absorbance and transmittance of radiation by the leaf of: (1) Red radiation, which chlorophyll absorbs; and (2) near infra-red (NIR) radiation, which chlorophyll transmits ,43 Figu. AbsorbaA different approach to estimating the relative leaf chlorophyll content is through the chlorophyll fluorescence emission ratio of red and far red radiation ,46,47,48Several chlorophyll meters are currently commercially available  and theyNumerous studies have reported strong relationships between chlorophyll meter measurements and the extractable chlorophyll concentration in the form of curvilinear relationships with a degree of saturation of measurements at high chlorophyll contents ,51,52. SAll chlorophyll meters are, generally, easy to use, do not require any particular training of users, and make measurements very rapidly with no or very little data processing . Calibra2 of SPAD up to 1250 mm2 of MULTIPLEX), appreciable repetition and strict sampling protocols are required for representative measurement. Measured values should be the average of, at least, several individual readings per field . Normally, each individual measurement is made on a unique plant [Given the relatively small sampling area  for monitoring crop N status, as part of the EU action Efficiency in Use of Resources for Optimizing Potato Production (EUROPP) . In thesA narrow range of crop N content may also have been responsible for the weak relationships between SPAD measurements and plant N content reported for greenhouse-grown cucumbers . This laDuring the last 20 years, there has been substantial research on the use of proximal reflectance sensors to assist with crop N management ,19,27,79The wavelengths selected for N assessment are chosen because of their sensitivity to changes of chlorophyll status, foliage density, and biomass that accompany N deficiency. These often correspond to four narrow bands, in order of importance, centered around 675 nm (red absorption maxima), 905 nm (NIR reflection peak), 720 nm (mid portion of the red-edge), and 550 nm (green reflectance maxima) ,78,84,85Reflectance sensors are classified as passive or active sensors depending on whether they have their own light source. Passive sensors normally have two sets of photodetectors, one set measures incident radiation above the crop canopy, and the other measures radiation reflected from the canopy; the measurement of incident radiation is used by the sensor to consider different irradiance conditions while operating. Newer, active sensors have a light source that emits both visible radiation and NIR. By modulating the light source, active sensors can distinguish reflected radiation from their own light source from that derived from ambient radiation , and so Crop reflectance measurements are one of the most promising methods for monitoring the N status of vegetable crops. One of their main advantages is that in an individual measurement they integrate the measurement of a much larger area than that measured by leaf level chlorophyll meters ,55. ManyA favorable practical characteristic of active proximal reflectance sensors is that no special requirement for uniform irradiance is required, which enables measurement under all ambient irradiance conditions ,101,106.In addition to crop N status, reflectance measurements and vegetation indices may be influenced by abiotic and biotic conditions, such as water status, irradiance and diseases, and pests ,108,109.Reflectance-based sensing of crop N status has shown promising results in many studies ,80,87. MSeveral studies have examined proximal canopy reflectance sensors in tomato crops, both for determinate processing tomatoes and for indeterminate tomatoes for fresh consumption. Gianquinto et al.  comparedIn greenhouse, hydroponic-grown cucumbers, using a custom-made CCD camera, NDVI, GNDVI, and RVI were strongly related to the leaf N status of upper leaves throughout the crop cycle ; the strThe ability of the canopy reflectance to assess broccoli N status was evaluated by El-Shikha et al.  using InA newer approach that has been used to monitor the crop N status proximally is based on the estimation of relative flavonols content from fluorescence measurements . FlavonoTwo fluorescence-based flavonols meters are most commonly used for estimation of flavonols content, being the DUALEX and MULTIPLEX . The DUAOne of the advantages of fluorescence-based flavonols meters for crop N monitoring is that the fluorescence measurement is essentially chlorophyll-based, and the soil does not interfere with the fluorescence signal the sensor receives . This isMeasurements with fluorescence-based flavonols meters should be taken on a regular basis or at critical stages of the crop on representative plants randomly selected from the center of representative areas of farms or within plots in research studies. Measurements are made on the most recent fully expanded and well-lit leaf, between the stalk and the tip of the leaf, and midway between the margin and the mid-rib of the leaf. Care should be taken at collection and the measuring of damaged leaves should be avoided. Measurements should be taken from both adaxial (top) and abaxial (bottom) sides of the leaf for more accuracy  and wherThe time of day does not affect flavonols content estimated with flavonols meters ,38,48. FEven though flavonols meters are a recently developed approach for the on-farm monitoring of crop N status; data are rapidly accumulating that demonstrate their potential for crop N management. Research with flavonols meters has been conducted with a wide range of crop types and species, such as maize ,142,143,Most of the research with flavonols meters has been conducted with maize ,142,143 A number of studies have been conducted with greenhouse-grown cucurbits in soil. In muskmelon, flavonols content and NBI, measured with DUALEX, were very strongly related to crop N content and NNI for most of the crop cycle , suggestGiven that excessive N application is a common occurrence in intensive vegetable crops, the ability of proximal optical sensors to detect an excessive N supply is an important practical consideration ,66. UndeWhere luxury N uptake does occur, optical sensors may respond to an excessive N supply. Measurements from optical sensors did not exhibit a plateau response, but tended to increase at increasingly excessive N supplies and crop N status in the muskmelon, tomato, and cucumber ,58,59. FVegetation indices based on reflectance in the green and in the red edge are reported to be very sensitive to leaf and crop greenness ,90,150, Previous sections have dealt with the capacity of proximal optical sensors to evaluate the N status of vegetable crops. The capacity to interpret sensor measurements and apply them to optimal N fertilization is a necessary subsequent step . ConsideAbsolute (as measured) sensor measurements do not indicate a deficient, sufficient, or excessive crop N status. To interpret sensor measurements in terms of crop N status, two main approaches have been proposed. These approaches are: (i) A relative approach using reference plots or (ii) an absolute approach based on the use of sufficiency values. A commonly-used procedure is to divide measured values of optical sensors by those measured in a well-fertilized plot without N limitations. The result is the so-called Nitrogen Sufficiency Index (NSI) ,152. TheThere are few examples of the use of reference plots in vegetable crops; however, most of the work with reference crops has been conducted in cereal crops ,158. WesEvidence has shown that saturation of optical sensor measurements does not always occur  and the An alternative approach to overcome the limitation of reference plots when saturation does not occur is the use of absolute sufficiency values of optical sensors measurements. Absolute sufficiency values of sensor measurements distinguish between deficiency , sufficiency , and excess  , whereasTwo approaches have, generally, been used to determine absolute sufficiency values: (i) Yield response and (ii) the use of indicators of the crop N status. Generally, yield-based sufficiency values have been derived from linear-plateau segmented regression between optical sensor measurements and yield. Yield-based sufficiency values have been determined, using this approach, for chlorophyll meter measurements in processing tomatoes ,68 and cTo provide flexibility regarding planting dates, cropping cycles, and location, absolute sufficiency values can be related to the accumulated thermal time  and phenThe use of absolute sufficiency values may ease crop N management in a straightforward way. When optical measurements deviate from absolute sufficiency values, adjustments should be rapidly made to N fertilizer management to correct for non-optimal crop N status. In a semi-quantitatively approach, this can be done by making adjustments (adding more or less N) to a previous plan of N fertilizer applications ,53. The The use of absolute sufficiency values for crop N management with optical sensors may be affected by cultivar and growing conditions. Further research is required to validate sufficiency values with different cultivars and growing conditions .This review has shown that different optical sensor measurements and indices are generally capable of providing an assessment of crop N status in a wide range of vegetable crops. In scientific terms, the selection of a proximal optical sensor for crop N management should consider various criteria, such as the capacity to provide accurate information of crop N status throughout the entire crop cycle or at critical stages . An impoA very important aspect to take into account when selecting a proximal optical sensor for use by farmers is the cost and ease of use. The high cost of some optical sensors  makes them unviable for practical use in small vegetable farms and local enterprises, despite their accuracy. Some of these sensors can be considered as being scientific instrumentation that have been developed for research. Recently, different commercial houses have begun to sell more affordable sensors (<3000€) or even low-cost sensors (<1000€) that may represent effective alternatives to research-based sensors for practical use on farms.Ease of use is another issue to consider when selecting a proximal optical sensor for use on farms. Most sensors provide the value of the different measurements at the same moment of the measurement, but others require the subsequent use of different mathematical equations to calculate the value of the measurement obtained by the sensor. Subsequent data management will make sensors less useful in the practical context as farmers or technical advisors would have to use these equations to obtain the required value.This review has highlighted the potential for proximal optical sensors to assist in crop N management of vegetable crops and the practical issues associated with their use. Experience with vegetable crops is more limited than with cereal crops, such as maize and wheat. However, the research conducted with vegetable crops has shown the sensitivity of these sensors to detect crop N status. Chlorophyll meters, canopy reflectance sensors, and fluorescence-based flavonols meters were all able to evaluate crop N status of vegetable crops. The optimal choice of which sensor type for a given cropping situation will depend on the crop, farm characteristics, the grower, the availability of suitable sufficiency values, and technical support. Proximal reflectance sensors measure a large surface area of the canopy, which can appreciably reduce the variability associated with leaf-clip instruments that commonly measure small areas of individual leaves. Most reflectance sensors and some fluorescence-based flavonols meters can make continuous on-the go measurements, thereby, integrating large measurement areas. This may be advantageous in large-scale farms. Compared to passive canopy reflectance sensors, active sensors are insensitive to irradiance conditions, which is an appreciable practical advantage. Chlorophyll and fluorescence-based flavonols meters do not integrate erroneous signals from bare soil (unlike some canopy reflectance sensors), making them more suitable for early crop growth stages and for widely spaced crops.The use of proximal optical sensors for the evaluation of crop N status has potential for a more sustainable N management of vegetable crops. However, sufficiency values and algorithms that calculate N fertilization recommendations from optical sensors measurements are scarce for vegetable crops. Further research should aim to go beyond merely diagnosing crop N status and suggest precise N fertilizer requirements. It is envisaged that progress will be made in this field in the future, stimulated by the increasing environmental and societal pressure for sustainable crop N management in vegetable crops.