Development of Juntos, a community-based family support program for caregivers of children with congenital Zika syndrome, contained innovative approaches such as using mothers as facilitators, fast-track learning, and de-isolation of families affected by Zika. A community-based family group program for caregivers of children with congenital Zika syndrome (CZS) was developed based on an existing program for families of children with cerebral palsy and pilot tested in Brazil.Program managers developing group initiatives should consider fast-track learning approaches to adjust their intervention to make it more useful to participants.Clinicians and managers of Zika initiatives should consider that caregivers of children with CZS will likely benefit from the ability to engage and exchange with caregivers of children with other neurodevelopmental disabilities.Program managers delivering community interventions targeting caregivers should consider engaging expert mothers as group cofacilitators.Integrating emotional support activities into groups that address child development is important, and adds value. The 2015–2016 Zika virus outbreak in Brazil was unprecedented and resulted in the birth of more than 3,000 children with congenital Zika syndrome (CZS). These children experience multiple complex health conditions and have limited services to support them and their family’s needs.An existing family support program for children with cerebral palsy  was adapted to the Zika context in Brazil through expert consultation. The program was pilot tested at 2 sites among 6 groups of caregivers  from August 2017 to June 2018. Group observation and focus group discussions with facilitators and participants at the end of each session informed fast-track learning, which was used to tailor the program for future groups. Fast-track learning—adjusting the intervention in real time based on gathered feedback—was found to be a helpful process to inform and hone the program from its initial concept.The intervention, Juntos, is a facilitated participatory group program for caregivers of children who have CZS. The group sessions are cofacilitated by a parent of a child who has CZS and an allied health professional. The group meets for 10 sessions that last 4 hours. Each session includes an icebreaker, activities, and group discussions. Content covers practical information on caring for a child with a developmental disability including that caused by Zika. Psychosocial support forms an important component, and families are guided from the first week to define and develop their own communities of support. Six pilot groups were successfully run in Rio de Janeiro and Greater Salvador, Bahia. The groups gave positive feedback on acceptability and demand.The program has the potential to be an important tool for community health and social support services in South America in response to Zika. The program can also be applied to children with neurodevelopmental disabilities other than those caused by the Zika virus, which could be important in ensuring families of children with CZS are less isolated. There had previously been no severe health consequences associated with the virus, despite Zika having been known since the 1940s.,www.ubuntu-hub.org.Although CZS and cerebral palsy are separate conditions, because they have similarities, programs designed for caregivers of children with cerebral palsy could provide a strong foundation to adapt a program for the Zika context in Brazil.Because CZS and cerebral palsy have similarities, programs designed for caregivers of children with cerebral palsy could provide a foundation to adapt a program for the Zika context.From April to August 2017, we conducted a needs analysis to assess the potential value of a community-based program, based on GTKCP, for caregivers of children with CZS in Brazil. The needs assessment involved: (1) tracking and comparing emerging literature on the clinical presentation of CZS with existing literature on cerebral palsy; (2) conducting a literature review on the needs of caregivers of children with CZS and cerebral palsy in middle-income contexts; (3) meeting with caregivers, specialists, and other local stakeholders in Brazil to identify key gaps, challenges, and needs; and (4) reviewing emerging data from a sister study measuring the social and economic impact of CZS on caregivers. A full description of the needs analysis is available.–We found that providing some services for children with complex multiple impairments at the community level could be crucial to address the unmet needs experienced by families of children with CZS in Brazil and may be more affordable than centralized services (which may be difficult or costly to access). Families of children with CZS, particularly those children with more severe impairments, did not have enough access to specialized health and rehabilitative services and informal support groups, and formalized support for caregivers was also limited. There was some concern raised by clinicians that children with mild to moderate impairments stemming from Zika infection were less likely to attend rehabilitation and that these caregivers were an important group to be targeted. Other researchers have also reported on the additional services required to fully address the care needs of children with CZS and their families.Families of children with CZS lacked adequate access to specialized health and rehabilitative services, informal support groups, and formalized caregiver support.Given the results of the needs analysis that identified the unmet support needs of parents in Brazil and the positive reception of the principle of GTKCP for Brazil among local stakeholders, researchers at the LSHTM who had been involved in GTKCP and EIP felt that adapting GTKCP and EIP for the Zika context and Brazilian culture could be potentially useful. Partnership for the project was established between the LSHTM and 2 Brazilian institutions: the Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira (IFF) in Rio de Janeiro, and the Universidade Federal da Bahia (UFBA) in Salvador.This article describes the process of developing and piloting the intervention in Brazil, as well as the final program that was developed . We alsoAfter conducting the needs analysis, we developed and adapted the program through expert consultation, and then piloted the intervention using a multiphase approach. A protocol was established by the lead project researcher (AD) to measure feasibility of the pilot intervention.Ethical approval was obtained from the Instituto de Saúde Coletiva/UFBA Ethics Ref 2.369.348, IFF/FIOCRUZ RJ/MS Ethics Ref2.183.547, and LSHTM Ethics Ref 13608. Informed consent was acquired from all participants.To support the adaptation, advisory groups were established in Brazil and in the United Kingdom and included a range of specialists, as well as mothers of children with CZS.The GTKCP and EIP curricula were reviewed by the lead project researcher (AD) with other LSHTM colleagues , Brazilian colleagues , the GTKCP and EIP teams, and other key identified experts . The project lead is a physiotherapist with 15 years of programmatic experience, including in qualitative and participatory research and community-based rehabilitation in low- and middle-income countries. During a May 2017 workshop in London, the experts convened to discuss the preliminary findings of the needs assessment and to develop consensus on a first draft outline of the program, an initial timeline, constituency of the facilitators to lead the caregiver group sessions, and participant inclusion criteria.The project group developed a theory of change to describe how the program relates to broader societal participation of children with developmental delays, including CZS, and the pathways that determine the extent to which this intervention may be successful. The theory of change describes what changes are needed and the assumptions underlying the achievement of these changes.The theory of change linked outcomes with activities to explain how and why the desired change was expected to occur.Several areas of adaptation were identified through the emerging literature, clinical experiences of managing children with CZS, development of the theory of change, and by the GTKCP/EIP teams. These areas included recommendations to further strengthen and develop specific approaches to recognize and address caregivers’ psychosocial needs and other clinical issues in children with CZS that were not covered within GTKCP or EIP .The EIP groups are cofacilitated by an expert mother who has experience caring for a child with cerebral palsy and a rehabilitation professional  who is experienced in working with children who have developmental disabilities. This approach had not been used in GTKCP. A decision was made to pilot test group facilitation by an expert mother combined with a therapist and assess whether this would be effective.There is a wide range in type and severity of symptoms among children affected by Zika.Caregivers of children who have confirmed or suspected CZS but not other types of neurodevelopmental disabilitiesCaregivers of children residing at home and not currently requiring inpatient hospital careCaregivers willing to attend the whole program and living within 1 hour of the group meeting locationChildren of any age Children who may be receiving rehabilitation services to address individual needsIt was agreed that program inclusion criteria would be:More than 1 caregiver of a child  was allowed to attend the group meeting.From June to August 2017, the project lead researcher (AD) drafted the initial program, adapting the GTKCP and EIP materials with input from expert committee members, project teams in Brazil, and other experts .We piloted the approach during 2 phases with 6 different groups and used this information to finalize the program. A future analysis will report the feasibility of the program using qualitative and quantitative data analysis.The partners in Brazil (IFF and UFBA) identified a site coordinator (MS and SF) for each of the 2 pilot sites, the states of Rio de Janeiro and Bahia. The site coordinators’ main responsibilities were to manage the logistic components of the pilot groups, including identifying an appropriate location for the groups, recruiting facilitators, recruiting researchers, identifying participants, and liaising with local health providers.Rio de Janeiro and Greater Salvador, Bahia, were selected as pilot sites because they had a large population of children impacted by Zika. Recife, which the LSHTM team visited during the initial country visit, was not selected because several other intervention projects by other organizations were already taking place and contamination of outcomes was a concern. Three sites within Rio de Janeiro and 3 municipalities of Greater Salvador  were selected because of their proximity to families of children with CZS, availability of an appropriately sized venue, and willingness of the local relevant authorities to accommodate a group.Facilitators were identified by the site coordinators and approved by the project team lead. A total of 8 local facilitators were selected (4 therapists with experience in pediatrics and CZS and 4 expert mothers). In August 2017, a week-long facilitator training was conducted in Rio de Janeiro and led by a trainer who has taught the GTKCP program extensively. The trainer was international, and we used a translator for the sessions as well as materials in Brazilian Portuguese. The training involved education on facilitating a group, practice sessions with reflective learning and feedback, and opportunities for discussion. The project leads and site coordinators selected 2 pairs of facilitators to lead the first pilot groups based on their performance during the training week.Two researchers were identified by the site coordinators and approved by the project team lead. All the researchers had a background in psychology, but this was not a prerequisite for the role. The researchers participated in a 2-day training in July 2017 on the research approaches and data collection methods and on the fast-track learning approach that would be used to update and adjust the program content based on weekly feedback that they collected from the groups.In August 2017, the first 2 pilot support groups—1 in Rio de Janeiro and 1 in Greater Salvador—started meeting weekly. The Rio group had 7 families, and the Greater Salvador group had 8. There were 10 sessions for each group with a different topic each week. Researchers used 3 techniques to collect data to inform real-time feedback and fast-track learning about the content and processes of the session. First, researchers directly observed the sessions and noted the session flow, participants’ responses, and behaviors of participants and facilitators. Second, researchers conducted focus group discussions at the end of each of the 10 sessions with participants and (separately) with facilitators to obtain immediate reflections and feedback on the session content. The researchers recorded detailed observation notes about the session and comprehensive notes about focus group discussions that they uploaded to a password-secured Google Drive document for the content developer (TS) to analyze. Third, researchers recorded pertinent comments from participants, facilitators, and site coordinators on images, content, activities, practicalities, and logistics, which were made outside of the sessions. Weekly calls within 48 hours of the session occurred between the researchers and TS, which allowed for further explanation and contextualization. Content issues were recorded and reviewed to update the program in real time and for 4 weeks after the conclusion of phase 1 in November 2017.In December 2017, a 3-day training session provided facilitators and site coordinators with information on the changes to the program content and structure based on fast-track learning in the first pilot phase.Two additional support groups were established in each pilot setting , with the primary aim of ascertaining the feasibility of the intervention. These support groups had identical procedures for data collection, real-time feedback, and fast-track learning (February–June 2018). After the delivery of the groups, the intervention was further updated, improved, and finalized using the same processes as before. The 2 groups in Rio had 7 and 9 families, respectively, and the 2 groups in Greater Salvador had 10 and 7 families, respectively.Six groups ran between August 2017 and June 2018 across 2 phases. The children of the caregivers were 25 males and 23 females with an average age of 23 months (standard deviation=9 months) at their first session. Of the families included in all 6 pilot groups, all (n=48) stated the mother as the primary caregiver. The ages of the mothers (n=48) were 15–20 years (3), 21–25 years (17), 26–30 years (5), 31–40 years (18), and 41–50 years (3). Thirty-six mothers reported they were married, 3 divorced, and 9 reported they were single. Only 6 mothers reported being in work, with the most common reason for not being in work being that they cared for their child (n=34).During the second and third groups in Greater Salvador, held between January and June 2018, several children with non-Zika related developmental disabilities participated in the sessions. This was done for 2 reasons: (1) to increase the number of children participating because the number of children with CZS who met the inclusion criteria was quite low, and (2) to assess whether combining caregivers of children with CZS and those with other neurodevelopmental disabilities would be a positive experience.We focused primarily on the caregiver and the program, with some interaction with the family, community, and services at the activity and output levels as informed by our theory of change . The proFast-track learning meant that the intervention was updated and improved as new information was gathered each week about what was working or not. For example, practical or administrative issues, such as organization of transport for participants, were changed and updated in real time each week.Through fast-track learning, we updated and improved the intervention as new information was gathered each week about what was working or not.As a result of rapid participant feedback, we made several changes to the program. For example, we changed the title of session 8 (highlighting advocacy and empowerment) to “uniting our voices”; the original title “raising our voices” translated to “shouting out loud.” In a second example, participants felt that the images used in the first 2 pilots, which used images from GTKCP and EIP, did not adequately reflect phenotype, family behavior, and environment in Brazil. Therefore, as participants requested, we included images that reflected their lives to create identification and favor more adherence. A local artist was engaged to draw more culturally appropriate images for the later groups, which were perceived more positively. More representation of fathers in caring roles was also incorporated at this stage.How did you find talking about today’s subject?Did it raise any emotions or feelings that you did not expect?How have you been feeling this week?New innovations in Juntos, which were not in GTCKP or EIP, include information on the Zika virus, strengthened participatory approaches to engage participants with community inclusion and disability rights, and a concerted effort to improve male engagement,The predictability of the questions helps participants to become comfortable with sharing. By week 5, participants have explored much of their thoughts on emotions and feelings, and this then progresses to reflecting on the future.The feasibility assessment is not detailed in this article and will be described in a future article on the findings.Consensus on the final content of the program was reached through 2 workshops  in May 2018. One group in Greater Salvador was still running. However, feedback that had already been collected from the groups was deemed sufficient to be able to finalize the content. The workshops included the technical advisory committees, study site coordinators, and researchers (psychologists).The final program intervention is called Juntos, which means together in Portuguese and Spanish, to emphasize the importance of inclusion and mutual support. Intervention materials comprise a facilitator manual and participant materials, such as photographs, animations, and video footage. An allied health professional and an expert mother cofacilitate groups that meet once a week for 10 sessions. Support and guidance for facilitators is provided by project coordinators via telephone, email, and/or WhatsApp.Groups are held at local community facilities, such as health centers, offices of local organizations, or schools, to minimize participants’ travel time and to foster relationships between people who lived relatively near to each other. Nine sessions are only for the caregivers and their children, and 1 session is open for other community members to attend. The children who come are looked after in a separate room or space by volunteers, but they are present for some of the practical aspects whenever relevant. The sessions are participatory and use principles of adult learning theory.https://www.ubuntu-hub.org/resources/juntos.Supportive information was developed for the program that includes short videos on the program and different aspects of care. The individual modules, full manual, and supportive materials are available in English, Portuguese, and Spanish: Fast-track learning added value to the intervention development because it allowed inclusion of language, logistics, content, and culturally specific changes in real time. Participants’ feedback during the first pilot phase was utilized to revise the content , which may have made the overall content more useful for the later groups. The later groups were aware of this process and recognized some of the changes based on early peers’ feedback. In a context of relative distrust and research fatigue,The fast-track learning process demonstrated how participant feedback was valued and reinforced the program’s focus on caregivers, a group that has been overlooked in the wider Zika response.The integration of a component of caregiver emotional well-being in this group intervention demonstrates a novel approach to including psychosocial support to better promote emotional well-being as an integral part of health work, rather than being seen as a standalone effort. There is no single recognized theory of how participatory groups achieve their health impactsIn understanding pathways to change, the role of the expert mother appears to offer crucial encouragement to shared learning between caregivers and contributes to developing an egalitarian atmosphere, expanding care practices beyond traditional rehabilitation models.The expert mother appears to offer crucial encouragement to shared learning between caregivers and contributes to developing an egalitarian atmosphere.Groups were held in the local community so that caregivers could build strong local networks. This also increased interest from caregivers of children with developmental disabilities other than CZS and highlights the importance of de-isolating Zika from other causes of neurodevelopmental disability when developing community support programs. Juntos does not replace health care services but rather seeks to complement services by empowering other caregivers to optimize their child’s care and upbringing.We received positive feedback during the sessions that combined caregivers of children with CZS with caregivers of children with other neurodevelopmental disabilities. There was a recurrent expression of comfort among the caregivers when engaging with other caregivers in similar situations and circumstances that they were not as alone, unique, and isolated as they had perhaps feared. This was also seen in the sessions where non-CZS caregivers engaged and, in fact, there was a value perceived to understand that the challenges being faced were not unique to only caregivers of CZS. This was also reinforced frequently in session 8 of the Rio sessions, where an external speaker came from a local Down’s Syndrome organization to discuss their advocacy approaches; the sessions were always extremely well received by participants. Although the challenges facing children with CZS and their caregivers remain unique and, to a certain degree, still unknown, there may be an important value to ensure that there are also many common issues faced and a shared approach may be both efficient and useful.,The needs analysis that we undertook at the beginning of the projectBy the nature of its design, Juntos can potentially be implemented by a range of stakeholders, from nongovernmental organizations to public community services to primary health settings. This flexibility may mean that there is a stronger opportunity for Juntos to be scaled up. The universal primary health structure in Brazil—the Sistema Único de Saúde—could be an avenue to further explore. We see opportunities for public/private partnerships also. Cost is clearly a major factor in the potential for scale up. Facilitator training can be done in larger groups to reduce costs. In addition, if the facilitator therapists undertake the role as part of their existing work, these costs may be further reduced. However, we do feel that it is important to remunerate parent facilitators for their work and other costs, such as transport and refreshments, to ensure full participation of families.Strengths of this pilot include the development process being informed by a theory of change and reflective practice and robust methodology that allowed integration of rapid feedback. Real-time feedback and adaption enabled the development of a culture-specific and language-specific intervention, and the program was developed and refined to meet the needs of caregivers of children with CZS in Brazil. Running the program in 2 sites concurrently  was an important methodological choice for achieving better final version program. Brazil is huge and diverse, and although these 2 sites do not cover the breadth of diversity, piloting in more than 1 site and acquiring different feedback added to the strength of the study.Our study has limitations. We describe the intervention development, but assessment of feasibility and evaluation of replication and scale-up in other countries is now needed. More work is needed on forming a comprehensive facilitator training program, and further development of the intervention to include all children with developmental disabilities is warranted. If Juntos is found to be feasible, robust studies to evaluate the cost-effectiveness of the intervention will be needed.We developed and refined a participatory community-based group intervention to meet the needs of caregivers of children with CZS. Juntos has the potential to be an important resource for community practice. There is scope to expand across Brazil and in other South American countries and to children with other developmental disabilities.


The prevalence of Barrett’s esophageal adenocarcinoma (BEA) is increasing in Japan. Accurate assessment of lymphovascular invasion (LVI) after endoscopic resection or surgery is essential in evaluating treatment response. This study aimed to assess the usefulness of immunostaining in determining the extent of LVI in superficial BEA.We retrospectively included 41 patients who underwent endoscopic resection or surgery between January 2007 and July 2018. In all cases, 3-μm serial sections from paraffin-embedded resected specimens were used for hematoxylin and eosin (H-E) staining and immunostaining for D2–40 and CD31. Two specialized gastrointestinal pathologists (T.Y. and T.T.), blinded to clinical information, independently evaluated the extent of LVI from these specimens. The LVI-positivity rate was evaluated with respect to the depth of invasion, changes in the positivity rate on immunostaining, pathological characteristics of patients with LVI, lymph node metastasis or relapse, and course after treatment.H-E staining alone identified LVI in 7 patients (positivity rate: 17.1%). Depths of invasion were categorized based on extension to the submucosa (SM) or deeper. On immunostaining for D2–40 and CD31, additional positivity was detected in 2 patients with SM1 and 1 SM3, respectively; LVI was detected in 10 patients (positivity rate: 24.4%). LVI-positivity rates with invasion of the superficial muscularis mucosa (SMM)/lamina propria mucosa (LPM)/deep muscularis mucosa (DMM), SM 1, 2, and 3 were 0, 75, 28.6, and 55.6%, respectively.Combined H-E staining and immunostaining is useful in diagnosing LVI in superficial BEA, particularly in endoscopically resected specimens. Helicobacter pylori infection [In Barrett’s esophagus (BE), columnar epithelium replaces normal squamous epithelium in the distal esophagus owing to repeated esophageal inflammation, injury, and repair caused by regurgitation of gastric acid or bile , 2. The nfection . This chnfection , 9. The nfection ; thus, eSuperficial BEA, in which the depth of cancer invasion is limited on submucosa, is primarily treated with surgery and endoscopic treatment as it has low risk for lymph node metastases. In Europe and the US, the primary treatment modality for BEA is endoscopic mucosal resection (EMR) combined with radiofrequency ablation (RFA) , while iHowever, given the rarity of BEA in Japan, no guidelines have been established for endoscopic resection of superficial BEA. Currently, endoscopic treatment is performed according to the guidelines for esophageal squamous cell carcinoma. With the increase in the number of indications for ESD, a multicenter cooperative study reported the possibility of expanding indications for ESD to superficial BEA. In the absence of both LVI and components of poorly differentiated carcinoma, lymph node metastases were not observed in BEA measuring ≤30 mm in the maximum diameter and in those with ≤500-μm infiltration to the SM. However, D2–40 or CD31/CD34 immunostaining was not performed to examine the presence of LVI. Furthermore, no central pathological diagnosis was obtained . To dateThis retrospective study evaluated 41 patients with superficial BEA who underwent endoscopic resection or surgery between January 2007 and July 2018 at the Nagoya University Hospital. Those treated at other hospitals and who received preoperative chemotherapy were excluded. Data on clinical information, endoscopic findings, treatments, histopathological findings, and course after treatment were collected from the electronic charts.Pathological diagnoses were made according to the Japanese Classification of Esophageal Cancer 11th edition, published by the Japan Esophageal Society . New musSMM; Carcinoma in situ or tumor has invaded the superficial muscularis mucosa.LPM; Tumor has invaded the lamina propria mucosa.DMM; Tumor has invaded the deep muscularis mucosa.SM1; SM2; and SM3 involving ≤1/3 of the superficial, middle, and deep layers of the resected specimen, respectively  , 16 and LVI was microscopically assessed using the H-E- and immunostained specimens by two specialized gastrointestinal pathologists (T.Y. and T.T.) independently who were blinded to the clinical information. The evaluation of H-E and immunostained specimens were performed independently at different times (rather than simultaneously). LVI was defined as endothelial cells recognizable on D2–40- and CD31-positive cells and the presence of tumor cells in a space surrounded by these cells .p-value of 0.05 was regarded as significant. All statistical analyses were performed using the IBM SPSS Statistics software version 25  package.Continuous and categorical variables were presented as median (region) and number (percentage), respectively. Clinical parameters were compared using the Mann-Whitney U test and Fisher’s exact test for continuous and categorical variables, respectively. The log-rank test was used to investigate the survival rate. A The median age of the 41 patients was 67 years; the patient characteristics are detailed in Table Table In 7 patients, LVI positivity was noted using H-E-stained specimens alone (positivity rate: 17.1%), and the depth of invasion was evaluated to be SM1 or deeper. LVI was found in 10 patients (positivity rate: 24.4%) who were additionally diagnosed with LVI positivity on immunostaining for D2–40 and CD31. The concordance rate of LVI diagnosis between the two pathologists was 97.6% (40/41) for H-E-stained specimens and 92.7% (38/41) for immunostained specimens. The kappa coefficient for the two pathologists was 0.92 for H-E-stained specimens and 0.82 for immunostained specimens, which indicated almost perfect agreement. The LVI-positivity rates in SMM, LPM, DMM, SM1, SM2, and SM3 lesions were 0, 0, 0, 75, 28.6, and 55.6%, respectively. Overall, between H-E staining alone and immunostaining, LVI was consistently absent in 75.6% (31/41) cases. LVI was additionally detected on immunostaining in cases with SM1 . The latter subgroup included 15 patients. LVI was present in 3 (60%) of the patients with < 500 μm submucosal infiltration and in 7 (46.7%) of patients with ≥ 500 μm submucosal infiltration. No specific pattern of distribution of LVI sites was observed.Table The recurrence rate was slightly higher among patients with T1b disease. However, there were no significant differences in overall, disease-specific, and relapse-free survival between patients with T1a and T1b disease Fig. . RelapseThe results of this study show that combined H-E staining and immunostaining is useful in diagnosing LVI in superficial BEA, particularly in endoscopically resected specimens. LVI is directly related to lymph node/remote metastases in cancer patients –22. Thern = 4), the high positivity rate is noteworthy. LVI is usually assessed using H-E-stained specimens. In patients in whom assessment is exceptionally difficult, the results may depend on the pathologist’s subjective assessment [In this study, LVI was present in patients with depths of invasion of at least SM1. The differences from previous reports were probably due to the number of patients and the use of immunostaining to identify LVI in all patients. Additional immunostaining increased the LVI-positivity rate by 7% than H-E staining alone. In patients with SM1 lesions, this rate increased from 25 to 75%. Although the number of SM1 patients was small (sessment , 25. Parsessment –28; and sessment , 30. HerJapanese guidelines recommend endoscopic treatment for early esophageal cancer and early gastric cancer. Conversely, no treatment guidelines for BEA have been developed owing to lack of data. In this study, LVI was absent in patients with infiltration up to the DMM. In SM1 lesions, no lymph node metastases were observed when the criteria proposed by Ishihara et al. were fulfilled . This suThe risk of lymph node metastasis must be adequately evaluated. Many studies reported that LVI, detected on immunostaining for D2–40, was an independent prognostic factor for lymph node metastasis , 31, 32.As a result of immunostaining, LVI was newly diagnosed in some patients and ruled out in some cases despite positivity on H-E staining. Although we were unable to conclude statistically whether additional immunostaining significantly increased the LVI-positivity rate in comparison with H-E staining alone, immunostaining may be useful in individual patients. The LVI-positivity rate was high among those with SM1 invasion; this should be considered while selecting patients for ESD. Furthermore, it is important to be able to identify the presence of LVI for predicting future relapse in patients with SM2 and SM3. In addition, positive findings on additional immunostaining in endoscopically resected specimens may facilitate decision-making for further treatment and prevent unnecessary surgery. However, immunostaining is cost and effort intensive and should be considered carefully in limited-resource settings.The limitations of this study are the single-center retrospective design and small sample size. However, immunostaining for D2–40 and CD31 was performed in all patients with superficial BEA who underwent ESD or surgery, and the presence of LVI was examined. Furthermore, the proportion of surgically treated patients was relatively high; the number of evaluable cases with lymph node metastases was also large.Immunostaining for D2–40 and CD31 is useful for identifying the presence of LVI in patients with superficial BEA. This is essential for evaluating the need for additional treatment, particularly in endoscopically resected specimens. Prospective multicenter studies on ESD and surgery as treatment options for superficial cancer, are needed.


The Positive Youth Development (PYD) approach identifies adolescents as resources to be empowered rather than problems to be solved. All adolescents have strengths and will fully develop when these strengths are integrated with healthy resources in the diverse environments where they live and interact. The objective of this study was twofold: (1) to present the Positive Development Program for Adolescents living in rural areas (DPAR Program) and (2) to pilot test the intervention program. The DPAR program was evaluated using a repeated-measures design before and after the intervention, with an intervention group and a control group. The sample consisted of 176 adolescents between 11 and 15 years old  who belonged to two high schools with similar characteristics located in rural settings. A mixed-design analysis of variance was performed for each dependent variable. Results showed a significant increase in most of the study variables  and a significant decrease in alexithymia, as well as better academic performance. All this evidence indicates that the DPAR program is effective in promoting positive adolescent development and addresses the lack of programs based on the PYD approach in rural areas. In recent decades, models that focus on promoting competencies in adolescence have proliferated ,2,3,4 beThe present study is framed within the Positive Youth Development (PYD) approach, which highlights the importance of the adolescents’ psychological, emotional, and social wellbeing. It is based on the idea that adolescents have strengths that can be developed, rather than being the bearers of problems to solve ,7. From Today, although the philosophy and objectives of PYD are clearly articulated ,7, the mIntervention with adolescents requires understanding the factors associated with adolescent risk and the ways they acquire and master the skills needed to promote healthy development. Waid and Uhrich  recentlyThe three main PYD models are: The Five Cs model , the DevIn addition, Oliva et al.  developeThe three models have similar characteristics, and they all contain important positive youth development variables such as self-esteem, assertiveness, self-efficacy, and empathy as  shows. HEmpirical studies have shown that interventions based on a positive developmental approach maintain the benefits they produce in adolescents in the long term ,15. MoreAt the international level, we find some programs based on the 5C model: the 4-H youth programs with wide state coverage in the USA ,6, PositBased on the model of positive adolescent development by Oliva et al. , the aimThe DPAR Program takes into account four significant elements in positive adolescent development: family, school, peers, and community. In this regard, it differs from previous PYD programs, such as extracurricular programs with community participation ,20,23,24Based on the PYD model by Oliva et al. , the FivIn accordance with the specific objectives, the variables selected to evaluate the DPAR Program were the following: self-esteem, self-efficacy, and identification with the class were included as variables in the personal area see . Self-esThe social area includes the variables of relational skills, assertiveness, and conflict resolution skills. Social skills training is based on the importance of interpersonal relationships for good psychological adjustment ,33,34, iThe emotional area includes empathy and alexithymia. Empathy and emotional skills are strongly related, and they make it possible to acquire and keep friendships and manage social problems more effectively . EmpathyThe cognitive area includes the planning and decision-making variable. This complex skill is developed throughout adolescence and should be fomented in order to compensate for the imbalance that exists between cognitive and motivational nerve connections that produce a certain vulnerability and increase impulsiveness and risk-taking ,41. RespThe moral area includes moral values. Learning and integrating positive values significantly improves adolescents’ attitudes towards their environment and the development of prosocial behavior ,10,17,18Finally, academic performance has been included as a cognitive competence. In educational contexts, there has been constant interest in understanding the cognitive and behavioral factors that favor or hinder students’ performance on their academic tasks and the way these factors are related to their overall development ,44. MoreThe aim of the study was to pilot test the intervention. The program aims to target all the above variables in order to see whether they improve after the intervention. In this sense, the main objective of the present study was to carry out a pilot test of the psychosocial interventionThe hypotheses proposed are that, after implementing the program, the intervention group will obtain higher scores than the control group on self-esteem, self-efficacy, group identification, empathy, relational skills, assertiveness, conflict resolution, planning and decision-making, moral values, and academic performance; and lower scores on alexithymia.To evaluate the effects of the DPAR program, a repeated-measures (pre-test and post-test) quasi-experimental design was used with an intervention and a control group. The sample is composed of 176 students (50.6% girls and 49.4% boys) between 11 and 15 years old . These high schools generally have a large number of interim teachers, which limits the possibility of carrying out consistent projects over time. The work profile of the families is as follows: father with low-medium-skilled work, and 40% of mothers are housewives. The cultural context is characterized by low reading habits and little participation in associations; in addition, the opportunities are quite limited.To find out whether the intervention and control groups show differences on sociodemographic variables at pre-test, homogeneity analyses were performed. Tests for homogeneity revealed no significant differences between groups at pre-test on the variables: age, sex, year in school, and academic marks see .Various informative meetings were held with the selected schools to explain the objectives and methodology of the DPAR program in June 2016. The high schools were selected through non-probability convenience sampling based on their accessibility and previous interest in participating in this study. After obtaining parent permission and authorization, one school was assigned to the intervention group and participated in the DPAR program in the 2016/2017 school year, and another school was assigned to the control group and did not participate in the program. The instruments were administered in the students’ usual classroom by a professional who was not associated with the school, for a period of 45 min. The students were informed that their participation in the study was voluntary, anonymous, and confidential. None of the students refused to participate.With regard to the program’s structure, it consists of 21 units integrated into fivemodules: personal, emotional, social, cognitive, and moral competencies, in addition to introductory and closing modules see . All theThe intervention is structured in three phases:Phase 1. Preparation. This is a very important phase in the program because the preparation tasks make it possible to raise awareness and prepare the scenario for the practical incorporation of personal, cognitive, social, moral, and emotional competencies in the classroom. Previous tasks of contact, awareness, and program preparation are carried out with members of the educational community and former students in a large classroom in the school. This phase lasts one month and makes it possible to reach a consensus on the bases for the DPAR Program, preferably in the month of July, before the end of the school year. The actions carried out have the following two objectives: (a) to establish the philosophy of positive development in the school and the way it is included in the Curriculum Project of the School and the Parents’ Association; and (b) to create community involvement in the promotion of the adolescents’ positive development through the participation of former students of the school. First, time is allotted to meet the teachers and the Guidance Department team through formal and informal meetings about the DPAR Program, the way it is going to be implemented, and what its functions are. Second, a meeting is arranged with the members of the Parents’ Association and the families through a formal call for the presentation of the DPAR Program. Later, once the school year has begun, a letter is sent presenting the program and attaching a parental authorization to participate in it. Third and finally, the necessary material and/or human resources and the way to obtain them are established. In this first phase, the pre-intervention evaluation with standardized scales is also carried out with the students, both the students who participate in the program and a control group in the students’ regular class. This pre-evaluation is performed in one of the initial sessions of the program.Phase 2. Intervention. In this phase, the intervention tasks are carried out with students, teachers, and former students of the school. It lasts eight months and allows the development of personal, social, cognitive, moral, and emotional skills directly in the students who participate, and indirectly in the teachers, family, and community  Knowing about the negative view and pathologizing of adolescence; (b) Theoretically, knowing about the models of positive development, from the deficit model to the current models of positive development; and (c) Learning the intervention techniques used in the DPAR Program to participate in the sessions. To do this, the following process is followed: (a) The constructs of positive development are reviewed; (b) The intervention techniques to favor their development are presented; and (c) The content and development of the workshops with the students are learned in order to participate in the intervention sessions. On the other hand, the strengths and weaknesses of the school are evaluated in order to propose strategies that promote a warm and safe social climate for the adolescents’ greater well-being and psychological adjustment. In this regard, the aim is for the teachers to have good social-emotional skills and be able to relate to others and solve the problems that arise in the classroom and, in general, focus their work positively.With the family, also a secondary target, an informative and formative session is held before the end of the course that precedes the beginning of the implementation of the DPAR Program. Later, a dossier is sent with the contents, activities, and students on a quarterly basis to encourage them to participate in their children’s teaching and learning process. In addition, in a transversal way, various tasks the students have to perform at home necessarily involve the parents.The community refers to the former students from the different municipalities who have studied at the same school, reside in that context, and/or maintain some type of link with their town .A training workshop is held with all the participants on the philosophy of the DPAR Program and the structure of each session. Afterwards, a training session is held with each former student to develop the competence addressed on the day they are participating and the methodological indications to transmit their life project to the students.At the halfway point of the intervention, the ad hoc satisfaction questionnaire is administered to all the students anonymously to assess their satisfaction with the intervention, the aspects they would like to address in greater depth, and the skills they would like to see promoted.Phase 3. Closure and feedback on the program. In June, the students complete the post-intervention measures (post-test). The collection, analysis, and presentation of the results of the program to the entire educational community is carried out to constructively close the program.Self-esteem. To assess self-esteem, the Spanish adaptation by Echeburúa [cheburúa  of the Rcheburúa ) was useSelf-efficacy. The General Self-Efficacy Scale [strongly disagree and 4 represents strongly agree. Cronbach’s alphas were 0.81 (pre-test) and 0.89 (post-test).cy Scale , validatcy Scale , was useGroup Identification. Tarrant’s Group Identification Scale [on Scale , adaptedon Scale , was useEmpathy. To measure this variable, the Basic Empathy Scale by Jolliffe and Farrington [1 = strongly disagree, 5 = strongly agree). Cronbach’s alphas were 0.75 (pre-test) and 0.79 (post-test).rrington , adaptedrrington , was useAlexithymia. To assess this variable, the Toronto Alexithymia Scale (TAS-20) by Bagby, Taylor, and Parker [d Parker , Spanishd Parker , was useSocial Skills. Scale of Social Skills of Olive et al. was used [was used . It has Planning and Decision Making. The Problem Solving/Decision Making Subscale of the Life Skills Development Scale for Adolescents by Darden et al. [n et al. , adaptedn et al. , was useMoral Values. The Scale of Values for Positive Adolescent Development by Oliva et al. [a et al.  was usedAcademic Performance. To evaluate this variable, the average of the student’s grades in the first evaluation (in December) and at the end of the course (in June) was used. These grades are grouped into fivecategories, rated on a scale from 0 to 10 .The Statistical Package for the Social Sciences (SPSS) version 25.0 for Windows , was used for data analysis. The comparability of the intervention and control groups on the pre-test was assessed using independent t tests or chi-square tests. To evaluate the effects of the program on each of the study variables, several 2 × 2 mixed-design analyses of variance (ANOVA) models were conducted, with a between-subjects factor (intervention or control group) and a within-subjects factor (pre-test and post-test).This is the recommended analysis when working with non-random or pre-existing groups , as in te. Cohen  suggestet = –2.27, p = 0.024), conflict resolution , and planning and decision making .Analyses were performed to test for possible differences in pre-test means  between Mixed-design group (intervention/control) × time (pre-test/post-test) ANOVA models were performed on each of the PYD and academic grade variables, with group as between-subject factor and time as within-subject factor. In each case, we mainly focused on the group-time interaction effect, which would indicate a differential change between pre-test and post-test for the two groups. The descriptive statistics and ANOVA results are presented in F  = 6.79; p = 0.010; F  = 8.71; p = 0.004; F  = 5.48; p = 0.020; F  = 5.30; p = 0.022; F  = 9.09; p = 0.003; F  = 7.43; p = 0.007; F  = 12.14; p = 0.001; F  = 12.78; p ≤ 0.001; F  = 25.64, p ≤ 0.001, ANOVA results showed significant group-time interaction effects for the following variables: self-esteem , and a marginally significant change in the control group . The effect sizes (Cohen’s d) were larger in the intervention group (d = 0.79).Examination of simple effects  revealedp< 0.001), but not in the control group. The effect sizes were medium or large, ranging from 0.52 for academic performance to 0.94 for relational skills.For self-efficacy, relational skills, assertiveness, conflict resolution, and academic performance variables, statistically significant changes were observed in the intervention group .This study presented a pilot test of the DPAR Program , carrying out an annual school intervention and evaluating the effects in a sample of early adolescents. The results show significant improvements in the intervention group, compared to the control group, in the variables of self-esteem, self-efficacy, group identification, empathy, relational skills, assertiveness, conflict resolution, alexithymia, and academic performance. The results highlight the need to take the context into account, in this case the rural context, in any psychosocial intervention, and the use of the systemic approach  to carry out effective PYD-based interventions.The DPAR program focuses on promoting adolescent well-being through the development of competencies ,6 that fThird, following the recommendations of previous studies ,11,16, tFinally, several authors highlight the need to improve the methodology used to evaluate programs that promote competencies in adolescents ,68. TherThis study is consistent with the existing literature on the effectiveness of youth programs. The DPAR program has shown positive results that support and extend those obtained through other programs with different personal competencies such as self-esteem, self-efficacy, and group identification ,70,71,72In the case of the other cognitive skills, such as planning and decision making, our hypothesis was not confirmed. These results are similar to those found for the Adventure of Life program, developed by EDEX in Spain  where thThere were no statistically significant differences in moral values either. Similar results are obtained with the Emotional Instructional Program for Personal Growth and Self-Realization (PIECAP), where only the older students connect more directly with the interests and concerns raised . In addiThis study has some limitations that should be taken into account when interpreting the results. Generalization of the results to the urban adolescent population should be viewed with caution. The program should be adapted to the characteristics of the urban adolescent population, and its effectiveness should be evaluated in subsequent studies. A longitudinal study should also be conducted to test the stability of long-term changes observed in the intervention group and find out whether the benefits are maintained, as previous work has shown . FinallyDespite these limitations, it is important to note that this is the first study to include all the PYD dimensions, based on the model by Oliva et al. , with adThis study presents the DPAR program and evaluates its effects in a sample of early adolescents. The results support the initial hypotheses because significant improvements are observed in the intervention group, compared to the control group, in the variables of self-esteem, self-efficacy, group identification, empathy, relational skills, assertiveness, conflict resolution, alexithymia, and academic performance.In summary, this study shows the effectiveness of the DPAR Program, demonstrating that it is a quality program and generates an adequate fit between the scenario and the environment . In a ru


Education is a pivot included Decade of Action for Road Safety initiative, which has reduced deaths caused by accidents in developed countries. Given the circumstances of each country, a proper education program is necessary. Thus, the aim of this study was to develop the National Road Traffic Safety Education Program (NRTSEP) and reduce Road Traffic Injuries (RTIs).This study used a qualitative approach and was conducted in Iran. Data were obtained through sixteen semi-structured in-depth interviews from indifferent road safety and health promotion field experts as well as eleven focus group discussion (FGD) sessions conducted with participants from general population. Inductive qualitative content analysis was used to converge and compare themes through data. The initial pattern of the program was developed and subsequently, the designed program was validated and finalized by two-step Delphi method for the consensus of expert opinion.The following six main themes emerged from the analysis: target groups, program content, educational methods, instructors, resources and evaluation. The target group consisted of children, youth, parents, teachers, elderly, motorcyclists, cyclists, pedestrians, drivers, driver license applicants, instructors and administrators of driving schools, and specific groups such as the disabled, managers at different levels, and policymakers. The content of the program consisted of 27 items, including traffic laws and regulations, first aid, and medical emergencies. Educational practices and authorities were determined based on the target group and educational content. The most important resources of the program were human force and other cases, which can be managed in case of a lead agency. In the evaluation dimension, the cases such as mortality rate, hospitalization, behavioral changes, and other cases can be considered.The designed program should be implemented for all target groups for road safety promotion. The proper content was provided with proper educational methods and instructors for the target groups. A lead agency is needed to provide the resources and funding to run the program. In Iran, Road Traffic Injuries (RTIs) are the leading cause of injuries and the second leading cause of death , 2. In rBasically, in road accidents, three factors of human, road, and vehicle are identified as major components, and the quality and quantity of displacements will be affected by these three factors. Human is the most unknown and most important factor in the course of events and, with all the efforts of experts in various sciences, the human reactions in dealing with the events cannot be predicted. Many differences between human beings, including physical, mental, etc., lead to the unknown nature of humans, such that above 70% of the accidents are attributed to this factor. Although the human factor has its own characteristics in various communities, the human factor, versus other causes, is the most important and difficult part for controlling transportation systems . The anaThe behavior of pedestrians, motorcyclists, and cyclists is a human factor involved in the occurrence of traffic accidents. Due to the role of human factor in the occurrence of accidents, traffic safety education programs are needed to be implemented. The public needs to become aware that the issues of traffic and traffic accidents are vital to their health and safety. In order to reduce traffic injuries policies such as improving the behavior of road users are implemented in countries such as Australia that are pioneering the reduced RTIs and crash fatalities  . In GerDifferent studies in Iran has shown that, despite the implementation of specific laws such as the use of seat belts, the rate of deaths has had small decline without education, demonstrating the need for education and cultural development in the country , 15.Therefore, the role of education in reducing traffic accidents is inevitable and the educational programs for the population must be provided and implemented based on the resources and facilities as well as the environmental, economic, political, and cultural conditions of each society.Considering the human factors for the occurrence of accidents from 2006 to 2016 in Iran, it is concluded that most of these factors can partially be eliminated through education. The major factors, including violation of traffic laws , 16–19 aAs part of the project for developing the National Iranian Road Safety Program, this qualitative study was conducted to develop a National Traffic Safety Educational Program (NRTSEP) in 2019. Semi-structured in-depth interview and focus group discussions (FGD) were used to collect data. Participants in the needs assessment were recruited from of different setting of Tabriz and the traffic experts from Tehran, Mashhad and Shiraz were interviewed. In order to gain a different viewpoint, a purposive sampling method was applied to insure that participants with varying levels of socioeconomic status, age, educational level, job, personal or family accident records, and driving violations were present in this work. At the beginning of interviews, all of participants were informed about the aim of the study.Overall, eleven FGD were conducted with different groups including mothers with young children; parents with students; the elderly; professional drivers; motorcyclists; cyclists; high school students; university students;, teachers; offending drivers and elementary students. Sessions were performed in convenient places in reach for all the participants. Each session lasted for about 1 hSixteen semi-structured interviews were conducted with stakeholders and experts on road safety and health promotion in Tabriz¸ Tehran, Mashhad and Shiraz as well as various organizations with the same conditions a Ministry of Roads and Urban Development, professors and experts of Ministry of Health and Medical Education, police experts, Ministry of Education, forensic medicine, Central Insurance Organization, Iranian Red Crescent Society, National Medical Emergency, Law Enforcement Force, and IRIB. In the selection of participants, the heterogeneous method  was used. Sampling was continued until data saturation reached, that is, no new codes were identified in the data. The semi-structured interview guide forms were used for the interviews, for which the literature review and opinions of various professors in the fields related to the subject and the research team were used. The interview began with the open-ended questions, such as “Which groups should be taught to reduce traffic accidents?” and continued with these questions “What content should be taught?” and “Who should be taught?”. After each question, participants were invited to explain more about what they had reported. The interviews were performed at the expert office’s or at a convenient public place. Each interview lasted 60–120 min.Based on the results of previous stages (needs assessment of people and experts) and the opinions of the research team, a primary suitable educational program was formulated. Then, selected educational program were entered into the Delphi survey phase.Inductive qualitative content analysis (a bottom-up method to explore the data) was employed based on the Graneheim method to converge and compare themes through participant data. Themes were clustered pursuant to participants’ views. In this method, the researcher recognized the themes based on the primary codes and categories. As such, the units of analysis are the entire interviews . Data anTo analyze Delphi method, each of the individuals scored each dimension and area of the educational program in two perspectives of importance (Does this perspective matter and should it be taken into consideration?) and applicability (Is there applicability for this area of the desired dimension?). In this section, the individuals first chose their general idea from three options of “Disagree”, “No idea” and “Agree” and, then, based on their previous choices, a score from 7 to 4 was given to each role given the previous option. In the information analysis step of this section, the scores were sorted from right to left. For example, the number 4 in “Disagree” was considered as 7 and number 4 in “Agree” was considered as 9. The number assigned to “No idea” was 5 .In order to confirm the validity of the program, the content validity index and modified Kappa were used. For validation in Delphi phase was two rounds of Delphi technique. The first round of the Delphi phase was conducted with 20 experts and scholars of traffic accident. Delphi forms were sent to individuals through emails and 2 weeks were given for completion; after this period, a reminder email was sent again. The second round of Delphi was conducted with 10 people. In this phase, 2 weeks were given to individuals to complete the forms. In this step, due to the high agreement of the first and second phases, the Delphi technique was finished and the program was finalized. Delphi questionnaire consisted of 9 points on the Likert scale and areas with scores above 7 were accepted and areas with mean 4–7 entered the second phase; areas with a score less than 4 were eliminated. The Content Validity Index (CVI) and modified KAPPA were assessed based upon expert perspectives. A minimum cumulative modified KAPPA score of 0.79 is expected to be achieved for the content validation.Overall, Six major themes emerged from the analysis forming the six dimensions of NRTSEP, including target group, program content, educational methods, instructors, resources, and evaluation. More information on themes and categories are presented in Table The first theme of NRTSEP was target groups which consisted of 12 groups needing to receive TSEP that included, preschoolers to university students, youth, teachers, parents, elderly, motorcyclists, cyclists, pedestrians, drivers, driving license applicants, instructors and managers of driving schools, Special groups , managers at different levels, car manufacturers and policymakers. More information on categories this theme, descriptions and sample of quotations can be found in Table In sum, we found that children below 18 years of age and students were very important target groups because they will be parents, managers, … in future.The second theme of NRTSEP was the content of program, which consisted of 27 educational contents that should be taught in different target groups. Table Overall, it was found that Primary, secondary and tertiary levels of education is given to target group.One of the elicited themes in the current study was the educational methods, including 12 categories namely; audio and visual media, practical training, modeling, simulators, Courses, Campaign, workshop, seminar, group discussion, material and spiritual fines, social networks, summary and reports. Table The majority of participants mentioned TV as the national media that can provide traffic education directly and indirectly for all the target groups. Other training methods must be used based on target group and educational content.The fourth elicited themes in the current study was the instructor, including 6 categories, namely TV, university and school teachers, instructors of driver’s license centers, parents, health workers and police.The most important instructor in the present study was TV as national media that can be successful in promoting traffic behaviors by broadcasting different programs to all target groups. TV can show the lost costs via subtitles by providing the costs and statistics related to blood money, death, and costs of traffic accidents and problems caused by high volumes of traffic, such as respiratory diseases, and provide specific training via special networks such as IRIB Salamat for survivors of accidents in the field of consequences, flashbacks, and psychological problems caused by accidents. It can also provide information about books published on traffic accidents and their prevention for different groups from various networks. TV also can show the phone number to report accidents and broadcast the experiences and trainings of successful countries in reducing traffic accidents. It can use the popular characters among the children and adults, such as Sia Saketi and Davood Khatar etc. (Well-known Iranian cartoon characters) In order to teach safe traffic behaviors and produce documentaries on the lives of accident victims and survivors. Also, a channel known as traffic channel can be established or a great deal of time can be dedicated to the traffic programs in the IRIB Salamat. According to an expert:TV has a key role in traffic education”.“Another category of instructor was school and university teachers that teach to target groups after being trained. A participant said:accept more what the teacher says”.“Students . An expert said: “the general academic course on traffic health and safety must be educated through trained teachers in universities for all fields”.Instructors of driver’s license centers were another category of instructor theme. As one participant said:“ driving is not just about introduction to driving skills, the correct behaviors and rules related to traffic both as a driver and as a pedestrian must be taught to the applicants through driving schools”.Other educational trustees were trained parents. They can indirectly teach by their right behavior to children.Mothers and fathers should be trained about safe traffic behaviors and observe these cases in the daily life”.“The other major instructor was Iranian health network rural health workers . Traffic behavior, like other healthy behaviors, should be trained trough health workers but the Ministry of Health has neglected it. According to an expert:Health centers as the accepted health promotion settings of people can have the important role in traffic behavior education”.“Police were another instructor in NRTSEP. An expert said:Police can train practical traffic behaviors in different settings such as schools, traffic parks, streets, etc. to establish behavior”.“Because of the interaction between the target groups, if all 6 instructors mentioned above are able to educate properly, safety traffic behavior can promote.This theme highlighted educational resources containing seven categories as; manpower; sufficient budget allocation and financial administrative support; proper technology; Providing materials and physical space; National Traffic Document; Strong monitoring systems; NGOs and charities.One of the most important resources required for the program is manpower. According to experts,Human resources must be trained with different skills and abilities, because it is at the macro scale across the country.”“ The majority of the experts in the present study believed that a lead agency is essential as a way of budgeting and resource management. All organizations must pay a part of their budget for educational contribution. Therefore, the resources are integrated and collected. An organization responsible for traffic at the macro scale According to experts,It must be determined who is responsible, the lead agency, traffic police, or the ministry of health? Each ministry should pay its own contribution. All the money should be collected and what has to be done with that money (integration and collection of resources), pooling, etc.” Given that the loss of human resources in society causes a severe economic and psychological burden on society, the cost is more effective with larger costs for teaching safe behavior as a prevention level. Another Expert said,“According to Lougou, if you think that investment in field of education is expensive, you must calculate the costs of ignorance.”“Another expert said,President Rouhani (Iran president)declared in 2015 that we have 3.5% negative annual income balance and a mortality figure of 32000 people per year (17000 due to traffic accidents and the rest for air pollution caused by traffic), and GDP of 6.4%. Therefore, if we prevent the losses caused by accidents, not only 3.5% negative annual income balance is compensated for, but also we will have 3% growth.”“Most of experts expressed financial resources are used to provide the budget required for providing educational content with proper methods and multimedia, software programs, applications, electronic content for virtual education, physical space for training, equipment of cycling, motorcycling and driving schools, proper space and simulators, new tools and technologies, and traffic laboratories to create a safe behavior in universities and research centers, software and hardware technology for registry of accidents.National traffic document was the important available resources that can be used for education of policy makers.A well-monitored audit structure is also necessary to spend the budget and expense considered in the program to build or modify the infrastructure. According to experts,A strong monitoring must be taken into consideration as important resources to prevent abuse of costs for infrastructure in the program.”“The advantages of donors, NGOs, insurance, and private companies can be used as program resources. Most of experts mentioned a lead agency can have the key role in resource organization for NRTSEP.The last theme of NRTSEP was evaluation, that consisted of five categories namely, Number of accidents and fatalities, Number of hospitalizations, Air pollution, Observation of traffic behavior before and after educational program and Satisfaction about the program.The purpose of the present study was to develop a national educational program on traffic safety promotion. The importance of education is to the point that one of the pivots of the Decade of Action for Road Safety 2011–2020 is education . One of In order to reduce accidents, hospitalizations, and problems and also to reduce its costs, an educational program is required to promote the user safety behavior given the environmental, economic, political, cultural conditions along with changes in the road network and increased vehicle safety. Based on the results of the study, the national educational program on road traffic safety promotion was designed in 6 dimensions. The main dimensions of this program included, target group, educational program content, teaching method, instructors, resources, and evaluation method.In the present study of the target group, included 12 groups of preschooler to university students, youth, teachers, parents, elderly, motorcyclists, cyclists, pedestrians, drivers, license applicants, instructors and managers of driving schools, special groups , managers at different levels, car manufacturers, and policymakers. In other words, based on the results of the present study, various levels of society should have traffic safety education. Similar to the present study, the PRSE (Permanent Road Safety Education) is continued for learning traffic culture from childhood to the end of life at all levels of society in the successful countries of the world on lowering traffic accidents, such as the Netherlands  ChildhooThe content of the present program consisted of 27 items Table , which iIn the present study, the educational methods included audio-visual media, practical education, role modeling, simulators, taking courses, campaigns, workshops, educational seminars, group discussions, social networks, financial and moral penalties, and brief reports, which is similar to the review study conducted by Jamaludin et al. . The teaThe participants of the present study considered IRIB and its programs as the most important educational authorities, which directly and indirectly affect the education and promotion of safe traffic behavior, and then, there are the teachers trained in schools who are responsible for education of students. In this study, the resources were human resources, appropriate technology, adequate budgeting and financial support, materials and physical space, national traffic document, strong monitoring system, and NGOs. In Turkey, Kenya and Egypt, NGOs have been involved in traffic safety promotion programs . The necExperts participating in the present study stated that the resources will be managed in case of a leader agency in the field of traffic in the country. This agency can monitor and evaluate the organizations’ function, lead the policymaking, and manage the resources, and therefore, the problem of inter sectional cooperation that wastes the resources will be resolved. In countries that have managed to reduce the number of injuries caused by traffic accidents, an agency or organization with sufficient authority is responsible for plans and activities to reduce traffic accidents and other organizations should have an interaction and collaboration with this agency , 42.The results of the present study showed that the educational program should be evaluated. For evaluation of program, the items included the frequency of deaths caused by traffic accidents, number of accidents and hospitalizations before and after training program, frequency of safe and non-safe behaviors before and after training program, satisfaction with program, and air pollution. Some programs have evaluated traffic behaviors after educational programs . Some ofThe present designed program must be implemented, and during implementation at various levels, the level of learning, impact on society, and long-term investment must be evaluated.Currently, the educational programs are implemented in a dispersed and island manner for some groups, but these programs need to be implemented continuously to reduce the number of accidents, deaths and injuries. This is the first program that was conducted as a needs assessment of people in different groups and was validated by Iranian experts.The weakness of the present study was that only residents of Tabriz were used in needs assessment and people from other parts of the country were not surveyed. The research team hopes that this program can be implemented, and changes in traffic behavior followed by a decrease in death rate can be seen.According to the people and professionals, Ministry of Education plays a key role in education and institutionalization of traffic behaviors, and the curriculum on traffic safety should be included in all grades and educational levels of students based on their age and are taught in a practical manner. Due to a high interaction between parents and children, the education of children will affect parents. Moreover, the television and radio should also provide the traffic education so that this interaction can continue to reach a safe traffic behavior. After the Ministry of Education and the media, the driver license centers are particularly important in education and promotion of safe behaviors. According to both groups of people and professionals, the education of managers at different levels and policymakers in establishing and modifying infrastructure and adopting and reforming laws are critical in the national educational program on traffic safety promotion. The experts particularly emphasized the need for a leader agency to manage the traffic accidents.


ARID1A loss-of-function mutation accompanied by a loss of ARID1A protein expression is considered one of the most important driver events in endometriosis-associated ovarian cancer. Although our recent genomic study clarified that ARID1A loss-of-function mutations were detected in 13% of ovarian endometriosis, an association between the ARID1A mutation status and ARID1A protein expression in ovarian endometriosis remains unclear. We performed immunohistochemical staining for ARID1A in 78 ovarian endometriosis samples and 99 clear cell carcinoma samples. We revealed that not only 70 endometriosis samples without ARID1A mutations but also eight endometriosis samples with ARID1A loss-of-function mutations retained ARID1A protein expression. On the other hand, most of clear cell carcinomas with ARID1A loss-of-function mutations showed a loss of ARID1A protein expression. In particular, clear cell carcinoma samples which harbor multiple ARID1A loss-of-function mutations or both a single ARID1A loss-of-function mutation and ARID1A allelic imbalance lost ARID1A protein expression. However, ARID1A protein expression was retained in seven clear cell carcinomas with ARID1A loss-of-function mutations. These results suggest that a single ARID1A loss-of-function mutation is insufficient for ARID1A loss in ovarian endometriosis and some clear cell carcinoma. Further driver events may be needed for the malignant transformation of ovarian endometriosis with ARID1A loss-of-function mutations. ARID1A) gene is located on chromosome 1p36.11 and encodes ARID1A, a key component of the SWI/SNF complex1. The SWI/SNF complex plays an important role in chromatin remodeling and is associated with numerous biological functions, such as differentiation and proliferation2. Therefore, aberrations in the SWI/SNF complex subunits have the potential to cause cancer. In particular, ARID1A, which is well known as a tumor suppressor gene, is frequently mutated in a wide variety of cancers4. COSMIC data demonstrated that more than half of ARID1A mutations are loss-of-function mutations, including frameshift indels mutations, and nonsense mutations, that lead to a loss of ARID1A protein expression in cancer cells5.The AT-rich interaction domain 1A , mutations in tumor suppressor genes such as PTEN, ATM, and TP53 were not detected in any of the 15 ovarian endometriosis samples.We assessed ARID1A immunoreactivity in 15 frozen section samples derived from six ovarian endometriosis patients . There were no differences in other characteristics according to the ARID1A mutation status  showed a loss of ARID1A protein expression  without ARID1A mutations also demonstrated a loss of ARID1A protein expression. The presence of ARID1A loss-of-function mutations was significantly associated with the loss of ARID1A protein expression in clear cell carcinomas (P < 0.001) .ARID1A protein expression was observed in 9 of 56 clear cell carcinoma samples (16.1%) with 1A Table . AlthougTo confirm concordance of the ARID1A staining level between frozen sections and FFPE samples, we prepared frozen sections and FFPE samples from the same patient. ARID1A immunohistochemical staining of frozen sections was similar to that of FFPE samples in two clear cell carcinomas and ovarian endometriosis case , no significant differences in any clinicopathological characteristics, including prognosis, were observed  samples from 47 patients without ARID1A mutations  ovarian clear cell carcinoma samples harbored ARID1A mutations . All frozen tissue samples were cut from surgical specimens, embedded in Tissue-Tek O.C.T. compound  in a Tissue-Tek Cryomold (Sakura Finetek) and quickly frozen in liquid nitrogen as described in our previous study38. Briefly, after deparaffinization, antigen retrieval was carried out with Target Retrieval Solution  in a microwave for 20 min at 98 °C. Subsequently, the sections were incubated with the primary antibody (1:500 dilution) overnight and biotinylated secondary antibodies  for 1 h, followed by incubation with ABC reagent (Dako) and 3,3′-diaminobenzidine (Sigma-Aldrich) for 3 min. Slides were counterstained with hematoxylin.Immunohistochemical analysis of ARID1A protein expression was performed for frozen tissue section and FFPE tissue section samples. A polyclonal rabbit anti-ARID1A antibody  was used for immunostaining as a primary antibody. Frozen tissue sections (6 µm) and FFPE tissue sections (5 µm) were cut with a cryostat and a microtome, respectively. FFPE tissue sections were stained as previously describedWe fixed frozen tissue sections with 4% paraformaldehyde at 4 °C for 20 min followed by methanol at − 20 °C for 10 min. The immunohistochemical staining protocol after fixation was the same as the protocol for FFPE tissue sections.39. We evaluated samples with more than 80% positive cells as ARID1A positive and samples with under 20% positive cells as ARID1A loss  The distribution of the percentage of positive cells showed bimodality as a previous studyTo validate the mutation status of ovarian clear cell carcinoma FFPE samples, we prepared FFPE serial section following the one used for immunohistochemistry assay to perform Sanger sequencing per FFPE sample. We isolated tumor cells by needle macrodissection and extracted DNA using a QIAamp DNA FFPE Tissue Kit  according to the manufacturer’s instructions.https://bioinfo.ut.ee/primer3-0.4.0/). PCR products were purified and sequenced by GENEWIZ .We performed polymerase chain reaction (PCR) using a KAPA Taq EXtra HotStart ReadyMix PCR Kit, and the primers used are listed in Supplementary Table https://www.r-project.org). We compared categorical variables between two groups by Fisher’s exact test and continuous variables between two groups by the Wilcoxon rank-sum test. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Deviation in the mutant allele frequency (MAF) of the somatic mutation from 0.5 was assessed by a one-sided binomial test. A P value < 0.05 was considered allelic imbalance40.We conducted all standard statistical tests with the R program (Supplementary Information.