A participatory evaluation event with a sample of Program Dharma community-based agents highlighted several additional successes, including that the community appeared to welcome and value their services and were beginning to support the cost of project activities. Conversely, challenges included identifying dogs in the database during revisits, sustaining the costs of community member time spent working on Program Dharma activities and the costs of veterinary care, whilst avoiding dependency of owners on free veterinary services. The benefits revealed by the evaluation were judged to be sufficient to extend Program Dharma to new areas, whilst evolving activities to resolve challenges.The Indonesian island province of Bali experienced its first rabies incursion in 2008. Mass vaccination of the dog population has proven effective and rabies cases in dogs and people have decreased, however the virus is still circulating among the dog population. Vaccination coverage must be maintained until rabies elimination. Increasing efficiency and effectiveness of vaccination campaigns is therefore desired. Community engagement leading to preventative health actions by community members can reduce disease incidence and costs of control. Here we evaluate 2 years of a novel community-based dog welfare and rabies control project (Program Dharma) in the Sanur sub-district. The project engaged the services of people living in the project area with an interest or experience in dogs or community health services. These people spoke with owners within their own community about dog welfare and health, monitored owned and unowned dogs and increased owner and carer efforts to access vaccination and further veterinary services. The evaluation focused on a sample of dogs whose owners had been regularly engaged with project. Vaccination coverage was increased and there were no dog or human rabies cases reported in the project area; the percentage of the dogs that had never been vaccinated was reduced by an average 28.3% . The welfare of dogs improved from an average of 20.7% of dogs with visible welfare problems at baseline to 2.7% after project implementation. Roaming dog density observed on street surveys also decreased in all project areas (24–47% reduction dependent on  Rabies has spread throughout Indonesia and is maintained in the domestic dog population in the majority of the 33 Indonesian provinces . The IndMass vaccination of the dog population can lead to herd immunity and hence prevention of rabies virus spread and eventual elimination of infection in dogs and therefore people , 8. For Although the strategy of mass dog vaccination has proved to be successful in many countries , 11–14, desas (villages) in the Sanur area of Bali were selected for the intervention: Sanur Kaja, Sanur Kauh and Kelurahan Sanur, with a total human population of 24,373  and estimated dog population of 6,009 dogs (desa was comprised of between eight and 11 banjars (sub-villages). These desas had experienced their last human rabies death in 2010 and last reported dog rabies case in April 2012, but remained vulnerable to rabies as the virus continues to be reported in other areas of Bali. Rabies surveillance is supported by the use of integrated bite case management where any suspect bite case entering a health facility is reported for follow-up by a government livestock officer, to assess the biting animal for clinical symptoms. Brain samples of suspect rabid dogs are sent for examination using Direct Fluorescent Antibody Testing at the Disease Investigation Center  (Three neighboring 009 dogs . Each deteriner) .desa leaders because they had an interest or experience in dogs or community health services and lived in the same desa as the dog owners they would be expected to influence. Each T2 was responsible for one or two banjars; banjars vary in size and so smaller banjars were paired up. The T2s volunteered for approximately 10 h/week for Program Dharma for which they received a small financial incentive. Their primary responsibilities were to conduct informative and informal visits with dog owners and other locals during which they (i) assessed the welfare state of dogs , (ii) monitored dog care practices and (iii) maintained a digital record of all dogs in their banjar. They were also responsible for helping to facilitate Program Dharma social and educational activities in their desa, including “Health Days” where the community could access free preventative veterinary care for dogs, provided by the Bali Animal Welfare Association (BAWA) and local government livestock officers, including sterilization , rabies vaccination and de-worming. In addition, T2s were actively involved in “troubleshooting” dog-related concerns from locals, including encouraging dog bite treatment according to health department advice, promoting the use of an emergency hotline set up to handle emergency calls by the Bali Animal Welfare Association, facilitating within-banjar adoptions of unwanted dogs and puppies, and maintaining positive relationships with desa leadership. Dog owners were not expected to pay for Program Dharma services or for rabies vaccination accessed through government run annual vaccination campaigns.Program Dharma was designed around a theory of change  to contrdesa was assigned one T1 as village coordinator. T1s were trained over 6-weeks, receiving in-person sessions on animal behavior; health and welfare; rabies signs, symptoms and prevention; community engagement strategies ; leading, managing and mentoring; and data collection and monitoring strategies. The sessions were designed and delivered through collaboration between BAWA, Udayana University and the International Fund for Animal Welfare (ifaw).The T2s were trained and managed by mentors, mostly recent graduates of Udayana University with degrees in Veterinary or Public Health, termed T1s see . In addidesa leadership to facilitate ongoing project support. The field coordinators spent between 1–10 h/week on Program Dharma activities. Program Dharma received support from ifaw who provided guidance and adaptive management, data analysis and periodic evaluation.Five Udayana University field coordinators and staff from BAWA provided additional oversight to the T1s, and they were also responsible for liaising with local government departments including the Dinas for Animal Health-Denpasar to coordinate government-sponsored rabies vaccination activities and A theory of change for the how the Program Dharma intervention contributed to rabies control is provided in desas. Program Dharma also supported the local veterinary authorities in accessing dogs for their government funded rabies vaccination leading to 3103 vaccinations in 2016, 3,576 in 2017 and 3,381 in 2018.From launch in May 2016 to June 2018, Program Dharma completed 621 dog sterilizations (unowned dogs prioritized for sterilization) during the 74 “Health Days” across all three https://www.icam-coalition.org/project/indicators-project/), presence of a visible skin problem, presence of visible wounds, rabies vaccination status, breeding status and confinement. A dog was categorized as in “poor welfare” if observed to be suffering from any of the following conditions: body condition score of emaciated or thin, visible skin problem or a visible wound. Confinement was based on the owners report of the method of confinement used for the majority of the dog's average day, including house and/or yard , kennel or cage, tether or chain and free to roam. Whether this method of confinement was effective, e.g., whether the yard boundary was truly dog-proof, was not investigated during the visit. Further details of the methods used to score transient details are also described in Hiby et al. , 277 (13.2%) received three visits, 272 (13.0%) received four visits, with decreasing frequency until only one dog received the maximum of eight visits. This sample compares the population of dogs at baseline with the same dogs at their most recent revisit—thus testing the hypothesis that being part of Program Dharma improves dog welfare and vaccination status. This sample represents 35% of the 6,009 dogs found during the census baseline conducted between May 2016 and May 2017  or their most recent revisit had been >12 months previously .A sample of 2,098 dogs were included for analysis, these were all the dogs that had received at least two visits from a Program Dharma team member and where the most recent visit had occurred in the previous 12 months (between June 2017 and June 2018). Most dogs received two visits , including nearly all of the T2s. The T2s mostly worked through the participatory exercises in desas; Sanur Kaja (n = 519), Kelurahan Sanur (n = 761) and Sanur Kauh (n = 818). Almost all dog-owning households gave consent to be interviewed at first request, when concerns were raised, a repeat visit accompanied by representatives from desa leadership was usually sufficient to reassure the dog owner of project legitimacy. Only 3 households were recorded to continue to refuse participation. The 2,098 dogs were comprised of 22.6% “Bali dogs,” a recognized breed native to Bali, 44.8% were identifiable as other breeds and 32.6% were mixed-breed dogs. There was a slight skew toward male dogs  and the vast majority were owned dogs (98.3%) with a few unowned dogs (1.7%). n = 556, 26.5%). This population composition  was not significantly different to the population reported at the baseline census, although the proportion of unowned dogs was higher at baseline (3.3%) . The remaining had been given away to another household , disappeared  or been sold . The time between baseline and revisit varied between dogs hence these fates of dogs that had left the household occurred over a timescale ranging from 13 to 757 days (average 443 days).The 2098 dogs lived in three e (3.3%) . At the desas showed a decrease in the percentage of dogs that had never been vaccinated against rabies, from between 41–49% at baseline to between 11–19% at most recent visit; an average decline of 28.3%  and Sanur Kaja  have shown an increase in the proportion of dogs with a current vaccination as compared to unvaccinated/lapsed. However, in Kelurahan Sanur , although the proportion of dogs that had never been vaccinated decreased, the proportion with a lapsed vaccination increased, leading to a non-significant change in the proportion of dogs with a current vaccination status in that desa.All of 28.3% . Althougdesas . The percentage of dogs with poor physical welfare (defined as poor body condition and/or a visible skin problem and/or visible injury) was significantly reduced at the most recent revisit as compared to baseline in all three desas, see 2 = 0.0488, p = 0.825, Sanur Kaja: McNemar X2 = 0.381, p = 0.537, Sanur Kauh: McNemar X2 = 7.682, p = 0.00558).Sterilization of dogs was performed at Program Dharma “Health Days” and independently by private vets. There was an increase in the percentage of dogs that were sterilized in all three n = 165), potentially contributing to an improvement in their welfare. The cells in red are dogs that were once roaming or confined to a house or yard and are now reported to be kenneled/caged or tethered (n = 64), potentially a welfare concern caused by a move to extreme confinement. Over the period of Program Dharma there was a change in confinement practices for dogs. In desas over time. In Kelurahan Sanur there was an average 47.2% reduction per year, equivalent to a reduction of 2.75 dogs per km of street surveyed in the first year ; in Sanur Kaja there was an average 23.6% reduction per year, equivalent to a reduction of 0.51 dogs per km of street surveyed in the first year ; and in Sanur Kauh an average 27.7% reduction per year, equivalent to a reduction of 1.04 dogs per km of street surveyed in the first year . The density observed in each banjar and individual best fit trendlines assuming an exponential decay over time is shown in There has been a statistically significant decline in the density of roaming dogs in all three The Program Dharma team, including the T2s, used participatory exercises to interpret the results from the data analysis and to develop agreed statements about Program Dharma successes and challenges. These statements were scored in terms of perceived importance using a combination of plenary discussion and participatory voting exercises where each participant had an equal number of “votes” to select the successes that mattered most to them and their community. The following lists the priority successes and challenges according to this scoring.Success statements:More dogs are physically healthy / there are fewer skinny or skin problem dogs.Owner knowledge of good dog care practices has increased.There is an increased knowledge of rabies prevention, both rabies vaccination of dogs and effective treatment of dog bites, this results in fewer instances of rabies related panic in the public.desas inspirational to othersProgram Dharma is an innovative program that makes Sanur We have built an accessible and dynamic estimate of the dog population in terms of numbers and vaccination status.desas.There have been no dog or human rabies cases in any of the Program Dharma Vaccination services are delivered more regularly to the community and the community knows about how to access these services.There are fewer roaming dogs on the streets.Owners treat their dogs better; providing food, water, kindness and rely less on caging and tethering.Challenges:The cost of providing veterinary care through health days is high and currently covered by the Bali Animal Welfare Association, this is unsustainable in the long term.Dog owners may be learning to depend on the free veterinary services provided by Program Dharma.Accessing local sources of funding to support the costs of Program Dharma is time consuming.The veterinary authorities will not allow Program Dharma vets to conduct rabies vaccination themselves, this must be done by government vets; these government vets are busy with many other roles and so vaccination services are delayed, vaccination coverage hence lower than it could be with Program Dharma vets allowed to vaccinate as well.Program Dharma has a social media presence that helps build awareness of the project and can be used to disseminate key messages about good dog care . But it takes time to craft and approve content and the numbers of likes and/or followers are still relatively low.It can be difficult to definitively identify an unowned in the database.It takes a long time to establish trust, active engagement and in-kind support from local authorities.Difficult to face complaints from community members who don't like dogs or have unrealistic expectations of solving issues with dogs.desas, the sample of dogs used in the analysis may have been a biased sample, as these are the dogs owned by people most engaged in Program Dharma as they have been revisited within the past year (between June 2017 and June 2018), other dogs living in the same community but not revisited by a Program Dharma representative may not have shown such improvements. Hence our study tests whether engagement with a community-based program improves welfare and reduces rabies risk, rather than can such a program change welfare and rabies risk across a whole community, regardless of the level of individual owner engagement. Particularly for rabies risk, where vaccination must be comprehensive throughout the population for effective herd immunity  combined with poor quality photo for dog recognition and recording the name of the interviewee as opposed to the head of household. As households are commonly comprised of extended families the interviewee name may be different to the main recognized family name for the household. These errors made identifying either the house or dog difficult. If there was a dog present in the household, but not identified in the database, it would be entered as a new dog. Hence some of the original census dogs were retained in the sample, although with a new later baseline, the number of these reentered dogs was not possible to calculate. These errors were noted early in the project and rectified as data collection protocols were refined. Permeant individual identification would have helped with finding dogs in the database. Alternatively, separate from the regular T2 visits, a specific data collection effort resulting in a repeated census or cross-sectional sample could have been used to monitor changes in the dog population.The evaluation event relied on analysis and interpretation of objective data but also on the subjective assessments of community representatives. During the evaluation event, the T2 groups were facilitated by their T1 village coordinator, this may have biased responses as village coordinators had a supervisory role with T2s. T2s and T1s had a close and positive working relationship, often visiting dogs and owners together, and appeared to use their shared experiences of Program Dharma activities to develop responses in a collaborative and non-hierarchical way. However, it would have been ideal to use facilitators without supervisory responsibility to avoid any potential bias. Further, as these representatives were engaged in Program Dharma activities themselves, they may have been biased toward seeing positive outcomes of Program Dharma. Future evaluations should look to include the perspectives of community members outside the Program Dharma team and should explore the vaccination status and welfare of dogs owned by people not re-visited by the program.desas showed an increase in current vaccination coverage during Program Dharma activity; however this increase was only statistically significant in two desas and not in Kelurahan Sanur. In Kelurahan Sanur there was a decrease in unvaccinated dogs but also a substantial concurrent increase in dogs with lapsed vaccination (vaccinated over 12 months previously), leading to the proportion of dogs with current vaccination status showing a statistically insignificant increase. Prior to Program Dharma, mass vaccination was delivered primarily through a central point strategy. A proportion of owners brought their dogs every year, leading to a low proportion of lapsed vaccinations. However, Program Dharma identified a population of dogs that had never been vaccinated via this central point approach. T2s were able to indicate to local government vaccinators where these unvaccinated dogs could be found allowing subsequent mass vaccination campaigns to use a targeted door-to-door strategy to reach them. Limited vaccine meant this reduced some central point efforts resulting in an increase in lapsed vaccination for those dogs that had relied on central point services. This appears to have been particularly pronounced in Kelurahan Sanur. However, the mass vaccination campaign uses as vaccine providing 3 years of immunity (Rabisin®) so a lapsed vaccination does not necessarily mean susceptibility to rabies. This approach appears to have prevented any rabies virus incursions as there were no reported dog or human cases of rabies during Program Dharma activity.Vaccination services were principally provided by local government (Dinas Pertanian Kota Denpasar). All desas in our study are extremely similar in terms of these predictors. Reasons for the less substantial increase in current vaccination and greater increase in lapsed vaccination in Kelurahan Sanur may be more to do with differences in how vaccine has being delivered during the annual mass vaccination campaigns than dog or owner characteristics.Predictors for rabies vaccination uptake in other studies in Indonesia have included dog owner socio-economic status, knowledge of vaccination campaigns, ability to handle dogs and characteristics of the dogs themselves including age and level of confinement , 21–24. desas, comparing dogs at baseline to their condition at the most recent visit by a Program Dharma, revealed a large and statistically significant reduction in the proportion of dogs in poor welfare . This improvement in welfare is proposed to be due to an improvement in care provided by owners following encouragement by Program Dharma and/or access to veterinary care provided through Program Dharma “Health Days.”In all three Over the period of Program Dharma activity, we observed a change in confinement practices with an increase in confinement of dogs within the household  and a decrease in all other methods of confinement. The reduction in kenneling/caging and tethering was desired as this is extreme behavioral restriction for a dog and hence has welfare implications. The reduction in free-roaming was desired as this would reduce the risk of road traffic accidents, feces in public places and potential nuisance for community members. However, dogs that have transitioned from free-roaming to caging or tethering are indicated with red cells in the transition matrix as there is a potential welfare concern for these dogs as they have moved from having relatively free movement to extreme confinement. Where confinement is to be encouraged, this must be done humanely to avoid both dog welfare concerns and potentially creating dog behavior problems for owners caused by a sudden increase in confinement.desas fell within the range of densities observed in seven locations reported in Hiby and Hiby  designed to track changes in dog care and welfare was also useful for identifying where unvaccinated dogs live for targeting during government mass vaccination; and has on occasion allowed reuniting of lost dogs.Implementation challenges include:- A large portion (45%) of the baseline dataset could not be identified during revisits.- Sustaining the benefits created through Program Dharma is economically most challenging due to the costs of veterinary care provided through “Health Days”; there is a risk of creating owner dependency upon free veterinary care through the program.desas contributing some local funding to cover this cost.- T2s were paid for the time they spent on Program Dharma, this adds another challenge to sustaining the program in the long term, although there has been some progress in addressing this challenge, with two of the three - Provision of vaccination services is currently restricted to local government vets, Program Dharma veterinary staff were not permitted to vaccinate dogs. This reduced vaccination opportunities and hence coverage was lower than it could have been.This first evaluation of a novel community-based approach to dog welfare and rabies control reports several beneficial impacts for vaccination coverage, dog care and welfare; as well as challenges to implementation. The benefits were judged to be sufficient to evolve and extend Program Dharma to new areas. Although this evaluation focused on a sample of dogs that had been recently revisited by T2s, future evaluations will have the opportunity to explore Program Dharma impacts in the wider community.ellyhiby@gmail.com.The datasets for this manuscript are not publicly available because they contain dog owner personal details required by T2s to acomplish revisits. Requests to access the datasets should be directed to Elly Hiby, The research aspects of Program Dharma underwent ethical review and received ethical clearance, No 356KE-PH-Lit-3II2018, in the Faculty of Veterinary Medicine, Udayana University, Bali. All data collection was conducted in accordance with the Declaration of Helsinki, participation was voluntary, following prior informed consent.KNA, EH, JG, NU, IMS, SP, IBNS, KKA, PJ, and DW: conceptualization. KNA, EH, JG, NU, IMS, SP, IBNS, KKA, and DW: methodology. EH: software. EH, LH, and MH: formal analysis. JG, YH, LK, GB, HI, NU, and KKA: investigation. NU and EH: writing—original draft preparation. IMS, SP, IBNS, KKA, PJ, IMIS, and DW: writing—review and editing. All authors contributed to approving the submitted version. KNA: funding acquisition.LH was employed by company Conservation Research Ltd and declares no competing interests. The remaining 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.


Professional burnout among medical trainees has been identified as a national concern in need of attention. A significant challenge for residency programs is designing and implementing effective strategies to promote resident wellness and reduce burnout. Emerging evidence highlights the importance of developing organizational changes targeting physician burnout.To address this critical need, Harvard South Shore (HSS) Psychiatry Residency Training Program aimed to assess burnout among residents, identify areas for wellness-related growth, and implement strategies for organizational change to reduce burnout and increase wellness. We aligned closely to the Standards for Quality Improvement Reporting Excellence (SQUIRE) 2.0 guidelines to systematically approach planning, conducting, and evaluating this quality improvement effort. We developed a wellness action team and assessed burnout using the Copenhagen Burnout Inventory (CBI). We also conducted a survey to investigate high opportunity areas for wellness-related growth and using this data we designed and implemented four organizational initiatives to (i) improve residents’ on-call experience, (ii) increase social activities, (iii) support preventative care, and (iv) promote wellness education. We then re-assessed burnout 1 year after implementation and performed two-sample t-tests to compare CBI scores. We additionally gathered and analyzed feedback from residents on the implemented organizational initiatives’ relevance to wellness and their well-being.There was an overall clinically meaningful reduction in burnout averaged among all residents that participated. Participants indicated that fitness-oriented activities were most likely to lead to change in wellness habits.Our implemented wellness program was resident-led and involved continuous feedback from both residents and leadership. Given that there may be multiple factors that affect resident burnout, future studies involving a control group could help reveal whether our intervention contributed to the change in burnout scores we observed.The online version of this article (10.1186/s12909-019-1756-y) contains supplementary material, which is available to authorized users. Burnout has been defined as a syndrome of emotional exhaustion, depersonalization or cynicism, and feelings of inadequacy regarding one’s work with patients . ProfessIn response to these outcomes, in 2017, the Accreditation Council for Graduate Medical Education (ACGME) revised their Common Program Requirements to address the need to reduce burnout and improve wellness among residents. Residency Programs have taken different approaches to meet this requirement but there is insufficient evidence for their efficacy . StudiesThe Mayo Clinic Program on Physician Well-being  has beenBased on the Mayo Clinic’s strategies, our residency program has built their own wellness program to assess burnout, identify areas for wellness-related growth, and implement strategies for organizational change. In this project we aim to assess burnout among residents at Harvard South Shore (HSS) and to evaluate the effectiveness of our own wellness program by gathering residents’ perspectives.Harvard South Shore is an ACGME-accredited Psychiatry Residency Training Program based within the VA Boston Healthcare System and affiliated with Harvard Medical School. The program lasts four years and has an average of 30 residents with about 8 residents per post-graduate year (PGY). The residents rotate through multiple different sites within the VA Boston Healthcare System, Harvard-affiliated hospitals and community hospitals.Current organizational dynamics at HSS allow for residents to drive program change through the development of resident-led action teams, and the Program Evaluation Committee (PEC). This committee allows for residents to provide feedback and be an integral part of program policy changes made by leadership. In addition, residents are encouraged to participate in quality improvement projects to learn about systems-level issues and to enhance their leadership and communication skills. Prior to this project, rates of burnout among current HSS residents and target areas for wellness-related growth had not been formally assessed. As part of ACGME’s efforts to emphasize wellness in residency programs, HSS leadership recognized the possibility of burnout among residents and encouraged the development of a resident-led wellness action team.www.squire-statement.org). This project has been reviewed according to VA Boston Healthcare System  procedures and has been determined to be a quality improvement activity that is classified as non-research, requiring no further oversight by the health system’s research committees.Four residents of different postgraduate levels formed the Wellness Action Team in March 2017 and initiated a quality improvement project based on Mayo Clinic’s strategies. We closely aligned phases of our project to the Standards for Quality Improvement Reporting Excellence (SQUIRE 2.0) guidelines to systematically approach planning, conducting and evaluating this quality improvement effort .We administered a survey to identify the residency program’s current strengths and weaknesses in promoting wellness  with the added benefit of increasing exercise; another important aspect of wellness. These sports leagues met for weekly games after regular residency working hours. To meet ACGME criteria, leadership emphasized the importance of preventative care as well as promoting wellness through education. This led to the addition of a designated ‘wellness day’ to our didactic curriculum and inclusion of mindfulness activities on regular didactic days (weekly). We also provided residents with a list of primary care providers  to facilitate access to preventative care. A summary of these changes is depicted in Fig. After leadership approved the addition of a wellness day as a way of promoting wellness in the program, members of the wellness action team started planning different activities for the day. The American Medical Association  defines We considered different burnout assessment inventories and opted to use the Copenhagen Burnout Inventory (CBI); a well validated psychometric test available in the public domain . The CBIFeedback from residents was gathered using paper-based surveys handed out during resident meetings  and the incoming class in 2018 (Class 2021 with 9 residents). 14 out of 23 residents  responded to the surveys at the start of the project and 12  after the intervention, one year later. The average CBI scores of the individual classes pre-and post-intervention are shown in Fig. p = 0.02). Overall, there appears to have been a clinically meaningful . Class of 2019 started out with the lowest burnout scores and was the only class that demonstrated an upward trend.The differences in scores between classes pre-intervention were not statistically significant. However, post-intervention there was a significant difference in the client domain score between Class of 2019 and Class of 2018  downwarThe majority of residents 94%) felt that Wellness Day addressed AMA’s fitness aspect the most, followed by the nutrition and emotional health (89%) aspects Fig. . As resi% felt thIn addition to assessing the impact of Wellness Day, we also attempted to identify what aspects of the overall project residents found most helpful in improving wellness. Most residents (85%) felt that the overall changes addressed AMA’s nutrition aspect the most, followed by fitness (62%) and emotional health (54%). Other than the switch in nutrition and fitness, the distribution is similar to Fig. As shown in Fig. Our efforts at HSS to reduce burnout and improve wellness among psychiatry residents involved four organizational initiatives – (i) improve residents’ on-call experience, (ii) increase social activities, (iii) support preventative care, and (iv) promote wellness education. Measured using the CBI, all postgraduate years showed an overall clinically meaningful reduction in burnout following the initiatives’ implementation.The average baseline burnout scores were slightly higher than those observed in other studies of residents, but they showed a similar pattern with higher scores in the personal and work domain and lower client-related burnout scores –31. As wWhile we were able to demonstrate a reduction in burnout, the extent of change differs between classes, with Class of 2019 showing an upward trend in burnout for the personal and client domains. As mentioned earlier, the etiology of burnout is multifactorial and residents’ responsibilities change as they progress in post-graduate years. For instance, generally the intern year tends to be quite demanding across different residency programs and even specialties, due to the steep learning curve one encounters after graduating medical school and realizing one’s responsibility for patients. This has been shown in other studies as an increase in burnout scores at the end of the academic year, particularly in the client domain , 30. It Beyond the measurement of burnout using the CBI, Wellness Day and the various improvements were also well received by residents. We attempted to address the residents’ request to improve the on-call experience by forming a food action team as well as an on-call patient task force. The food action team successfully improved the overall quality and quantity of food available when residents are on call. All residents perceived that this improvement was most relevant to their sense of wellness. On the contrary, only 30% thought that the on-call patient task force was relevant. This task force was implemented with the intention to improve work-flow and reduce workload on the individual resident when they are on call. However, unlike the mostly simple objective of the food action team, the task force needs to enact system-level changes that are likely more intricate and gradual. This underscores the need for projects such as ours to address resident burnout and wellness through organizational changes. On an individual level, residents will likely only feel the impact of this initiative over time.Due to the residents’ enthusiasm for Wellness Day and the reduction seen in overall burnout scores , program leadership agreed to incorporate an annual Wellness Day into the didactic curriculum. All other aspects of the project  are ongoing after completion of this pilot quality improvement project. Overall residents perceived the fitness activities  as well as Art Therapy most relevant to their sense of wellness, most effective in enhancing their understanding of wellness and most likely to encourage change in their own wellness habits. While all these opportunities continue to be available on regular working days, we did not assess whether residents actually incorporated them into their daily work schedule. Future research could address this and use the information for planning further wellness initiatives. This also highlights the importance of gathering resident feedback prior to developing wellness programs. While residents had voted against a session on financial health, many suggested to include this in the post-wellness day survey Additional file 2:System improvements for residents’ wellness; Survey to identify the residency program’s current strengths and weaknesses in promoting wellness. (DOCX 21 kb)Additional file 3:February Wellness Day Survey; Survey to gather feedback from residents regarding possible wellness day improvements. (DOCX 23 kb)Additional file 4:Outcome of Wellness Initiatives; Survey to identify which initiatives (including wellness day) were perceived to be most relevant to residents’ sense of wellness. (DOCX 19 kb)


Artificial neural network analysis (ANN) showed correlation efficiencies of physiological and molecular parameters using a concept-free approach. ANN analysis appointed PA as the mastermind of molecular level changes. Besides sedentary status, insulin and hTREC showed significant segregation. Biostatistics evaluation also supported the schism of participants for their sedentary status, insulin concentration and hTREC copy number. In the future ANN and biostatistics, may predict individual responses to regular exercise. Our program reveals that high responder individuals of certain parameters may be low responders of others. Our data show that moderate regular PA is essential to counteract senescence in young and healthy individuals, despite individual differences in responsiveness. Such PA may not seem important in the everyday life of young and healthy adults, but shall become the base for healthy aging.Studies support that regular physical activity (PA) decelerates senescence-related decline of physiological and molecular parameters in the elderly. We have addressed the other end of this spectrum: healthy and young, inactive individuals participated in a 6-month long personal trainer-guided lifestyle program. We have measured physiological and molecular parameters (differentiating high- and low responders) and their correlation with PA (sedentary status). Cluster analysis helped to distinguish individuals with high- or low PA and differentiate high- and low-responders of each parameter. The assessed cardiovascular parameters (heart rate, blood pressure, 6-min walking distance, relative VO Statistics show that regular physical activity (PA) helps preventing the development of several chronic diseases including cardiovascular events, malignancies , neurodePositive response to exercise is often generalized in literature assuming that the group average represents a typical response for all participants . Howevern = 3) and females (n = 22), the mean age was 24.95 years (±4.04). At the end of the program 14 participants  completed the 6 month-long lifestyle program fulfilling the requirements of attending trainings three times a week.The lifestyle program was a university-based trial designed to promote PA among physically inactive university students. The trainings were conducted in the Institute of Sport Sciences and Physical Education. The program was executed from November to May, it was approved by the ethics committee of the University of Pécs (ref. no.: 6439/2016). All participants gave written informed consent before starting the lifestyle program in accordance with the Declaration of Helsinki. All measurements involving human subjects and their blood samples were performed with the consent of the Regional and Local Ethics Committee of Clinical Center, University or Pécs according to their guidelines. We recruited 25 participants altogether via advertisements in social media. The inclusion criteria were: no regular PA or controlled diet program in the previous 6 months, no history of disease . Participants were both males . Every other week training was performed wearing Polar Team system heart rate (HR) monitors. Participants were asked to keep their usual diet and normal daily activity level during the 6-month long lifestyle program.Measurements were conducted before starting the training program (0 month), after 3- and 6- months. The 3- and 6-month values were normalized to baseline values and converted to Z-scores. Body Fat% and Muscle mass% were measured using Bioimpedance Analyzer . After 5 min at rest both systolic and diastolic blood pressures were measured (Omron M10-IT).2max (L/min) was calculated as described by 2max (ml/kg/min).Physical fitness was assessed by using a 6MWT, slightly different from the original protocol of Actigraph GT3X+  is a tri-axial accelerometer-based method of monitoring activity . ActigraR-R interval was registered every 2nd week during exercise sessions with a Polar Team System  following Baynard’s method . The traHeart Rate monitoring was accomplished according to recommendations . BrieflyFasting blood samples were taken in the morning. Subjects were instructed to restrain from exercise during the day before their examination. Venous blood samples were collected in suitable vacutainers, tubes containing potassium ethylenediaminetetra-acetic acid (K-EDTA) were used for testing cellular blood parameters. Tubes without additives were used to obtain serum for C-reactive protein (CRP) and cortisol tests. After blood collection serum was separated by centrifugation . Blood cell parameters were quantified in a multi-parameter automatic hematology analyzer Cell-Dyn 3700 system . CRP was measured by Cardiac C-Reactive Protein (Latex) High Sensitive turbidimetric immunoassay (Roche Diagnostics) on Cobas 8000 Modular Analyzer  following the manufacturer’s instructions. Cortisol was measured by Cortisol RIA Kit  on RIA-mat 280 automated analyzer  following the manufacturers’ instructions.TM 3D Digital PCR Reagent Kit (Thermo Fisher Scientific) recommendation. The Digital PCR sample mix was added on each chip and loaded on ProFlexTM 2x Flat PCR System following the manufacturer’s instructions. Absolute quantification of hTrec copy number was performed using QuantStudio 3D Digital PCR System (Thermo Fisher Scientific) then analyzed using Analysis SuiteCloud Software.Venous blood samples were collected in sodium citrate-containing tubes (BD Vacutainer Blood Collection Tube). Genomic DNA was isolated from 200 μl blood sample using Blood Mini Kit , allowing for sjTRECs  DNA loops to co-isolate with genomic DNA. Total DNA was quantified using NanoDrop 2000 . DNA was then diluted to a final concentration of 2000–3000 copies/μl. Digital PCR reactions were prepared according to the QuantStudiot-test.Evaluation of the dataset was carried out by Neurosolutions 6 (Neurodimension Inc.) ANN software of Jordan/Elman type. As being a highly adaptive system, this kind of network extends the basic multilayer perceptron model with context units remembering previous. The network can reveal the hidden relationship between input and output factors of no obvious connection. For network training 14 datasets were used (lifestyle program participants) throughout 10 000 training sessions with an average mean squared error of 0.003. Software. Significance was determined using simple Euclidean distance matrix was computed based on the acquired data. To detect any pattern in this dataset hierarchical clustering with complete agglomeration method was used. For key ANN parameters  we created dendrograms based on clustering results. In addition to visualize data pattern, 3D plots were also employed using NCSS version 12 statistical software.p < 0.05. Power analysis was also performed for confirmation . Please, note that both clusters show increasing activity by the end of the program .Physical activity of the recruited participants was recorded and evaluated. By definition inactive individuals spend a significant amount of time in sedentary status, hence increasing PA means that these individuals spend less time in sedentary behavior . Z-scorep < 0.01) and recovery- (p < 0.001) HR Z-score values. Blood pressure Z-score values obtained by cluster analysis (p < 0.001)   , while d < 0.01) .p < 0.01 at half time, and p < 0.001 at program exit)  showing slight decrease by the end of the program (p < 0.05). In support VO2max also shows a moderate decrease with time  . Since pvaluated . As expeith time , similarith time  and the ith time  Z-score p < 0.001). Muscle mass percent shows the opposite tendency, albeit the effect is more profound for HiR individuals at half time (left part of p < 0.01).Body-mass index (BMI) is calculated based on body mass and height. Regular PA is known to restructure body composition decreasing body fat content and increasing muscle mass . HoweverChanges in classical molecular parameters were also anticipated to occur during a lifestyle program. This section focuses on cluster analysis to differentiate high responders (HiR) and low responders (LR) based on molecular parameters, while the exact numerical values are listed in p < 0.001 to p < 0.01 for glucose, and p < 0.01 to p < 0.001 for insulin, comparing half time and final values, respectively). As for lipid metabolism, HDL and LDL cluster analysis results are shown by p < 0.01 for HDL and p < 0.001 for LDL).Regular PA is known to depend on and gradually reshape energy utilization, both fast-acting glucose and slow-acting lipid metabolism . For thiRegular PA is considered to enhance immune responses due to chronic low-level stress also known as hormesis . Since hp < 0.001) both at half time and program exit. CRP level Z-score values show the anticipated decrease in HiR individuals and a marked segregation of HiR and LR individuals at half time (p < 0.001) that unexpectedly diminishes by program exit (at 6 months p < 0.05). Elevated cortisol levels are known to suppress specific leukocyte counts e.g., lymphocyte counts (p < 0.001 at mid-term and p < 0.01 at program exit). Thymus function (fresh naïve T-cell production) has been reported to improve with regular moderate physical exercise (p < 0.01) that lessened by program exit (p < 0.001). Our data support that moderate regular exercise enhances thymus function (fresh naïve T-cell production).Cortisol levels increase following regular exercise in HiR individuals, and cluster analysis shows marked segregation of HiR and LR , Y-axis shows half time (3 months), and Z-axis shows program exit (6 months) values. 2D plots are available for all the assessed physiological and molecular parameters in Artificial neural network analysis above appointed sedentary status, insulin and hTREC as the most influential, and deregulated parameters. We applied further analysis for these parameters in order to examine the segregation of participants. We have created a concept-free hierarchical clustering with complete agglomeration. 2max gain diminishes  and immune  parameters as confirmed by ANN analysis . This isminishes  and muscminishes  at progrCortisol, a family member of corticosteroids, is also acknowledged as a hormone of adaptation that aids acclimatization to chronic low level physical stress triggered by regular exercise also called hormesis . CortisoCorticosteroids are potent anti-inflammatory agents . In our It has been reported that personal responsiveness relies on multiple factors, including genetics and environmental factors  . Fixed tOur observations provide novel information on individual differences in response to combined endurance and resistance training . PreviouA frequent misconception is to generalize data and present mean response alone, however, individual responses typically show remarkable variation, including segregation of high and low responders for each and every parameter. Using concept-free techniques, performing ANN analysis and biostatistics evaluation we have identified numerous molecular changes triggered by regular PA, and show evidence for individual responsiveness at molecular level. Our study proposes that ANN analysis combined with biostatistics evaluation – especially hierarchical cluster analysis – will help in the future to predict individual molecular responsiveness, however, more participants and further studies are required for proof-of-concept.The program was approved by the ethics committee of the University of Pécs (ref. no.: 6439/2016). All participants gave written informed consent before starting the lifestyle program in accordance with the Declaration of Helsinki. Experiments involving human subjects and their blood samples were performed with the consent of the Regional and Local Ethics Committee of Clinical Centre, University or Pécs according to their guidelines.KG performed many anthropometric and most molecular measurements, and involved in the manuscript preparation. ZA performed the statistical evaluation of the assessed parameters. RH executed biostatistics evaluation of the assessed parameters. TN designed and orchestrated, while EK executed most physiological measurements. SP performed the ANN analysis. AG planned and supervised the biostatistics evaluation. JP involved in trial design of molecular procedures and manuscript preparation. MW involved in anthropometric and physiological trial design, and manuscript preparation. KK orchestrated the current research, involved in the design of most molecular procedures, and took significant part in the manuscript preparation.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. The reviewer IB-M declared a shared affiliation with the authors and a past co-authorship with one of the authors RH to the handling Editor.


MW9.0 Tohoku-Oki megathrust earthquake caused medium weakening and stress perturbation in the crust around the Korean Peninsula, increasing the seismicity with successive ML5-level earthquakes at the outskirts of high seismicity regions. The average ML5-level occurrence rate prior to the megathrust earthquake was 0.15 yr−1 (0.05–0.35 yr−1 at a 95% confidence level), and the rate has increased to 0.71 yr−1 (0.23–1.67 yr−1 at a 95% confidence level) since the megathrust earthquake. The 2016 ML5-level midcrustal earthquakes additionally changed the stress field in adjacent regions, inducing the 15 November 2017 ML5.4 earthquake. The successive 2016 and 2017 moderate-size earthquakes built complex stress fields in the southeastern Korean Peninsula, increasing the seismic hazard risks in the regions of long-term stress accumulation. The increased seismic risks may continue until the medium properties and stress field are recovered.The distance-dependent coseismic and postseismic displacements produced by the 2011  The region around the peninsula is under the influence of a compressional stress field with an ENE-directional compression and SSE-directional tension7 on7 Fig. . The inson7 Fig. .Figure 18. The historical seismicity displays high similarity with the instrumentally recorded seismicity over most regions in the Korean Peninsula, except the central peninsula around the Seoul metropolitan area9. The historical earthquake records present high seismicity with large earthquakes in the central peninsula.However, the historical literature indicates large seismic damage on the Korean Peninsula. The largest seismic intensity reached IX on the modified Mercalli intensity (MMI) scaleMW9.0 Tohoku-Oki megathrust earthquake occurred ~1200 km from the Korean Peninsula. The megathrust earthquake incorporated large lithospheric displacements up to regional distances12. The 2011 Tohoku-Oki megathrust earthquake produced coseismic displacements of ~4 cm around the east coast and ~2 cm around the west coast of the Korean Peninsula 6. Small changes in the stress field and medium properties produce earthquakes with new fault planes whose orientations conform to the stress field11. Earthquakes with different faulting types occurred after the megathrust earthquake11, possibly due to abrupt changes in differential stresses that develop new fault planes with different faulting behavior24.The stress field inferred from the focal mechanism solutions of earthquakes after the 2011 Tohoku-Oki megathrust earthquake is close to the ambient stress field inferred from the focal mechanism solutions of earthquakes before the 2011 Tohoku-Oki megathrust earthquake. The compression-axis directions of the 12 September 2016 ML5-level earthquakes have occurred on the Korean Peninsula since 1978, when national seismic monitoring was commenced  occurred since the 2011 Tohoku-Oki megathrust earthquake. We investigate the properties of the successive ML5-level earthquakes and their induction mechanisms on the Korean Peninsula.Ten 12. Seismic velocities are recovered with time12. We examine the seismicity changes by declustering the seismicity, which excludes the aftershocks from the earthquake catalog . The declustered seismicity of earthquakes with ML ≥ 2.5 presents seismicity rates of 21 yr−1 (18.72–23.25 yr−1 at a 95% confidence level) prior to the megathrust earthquake and 31 yr−1 (27.13–35.53−1 at a 95% confidence level) since the megathrust earthquake . The occurrence rate prior to the megathrust earthquake, 0.15 yr−1 (0.05–0.35 yr−1 at a 95% confidence level) changed to 0.71 yr−1 (0.23–1.67 yr−1 at a 95% confidence level) after the megathrust earthquake. The probabilities of having five ML5-level earthquakes in the 7 years since the megathrust earthquake are less than 3% and 1% for occurrence rates of 0.25 yr−1 and 0.15 yr−1 in terms of Poissonian earthquake occurrence26 . This observation suggests that the recent ML5-level earthquakes since the 2011 megathrust earthquake may be time-advanced events that might otherwise have occurred at later times27.The seismicity before the megathrust earthquake may be a consequence of tectonic loading in the crust of the Korean Peninsula. The average occurrence rate of the ten ML5-level earthquake (ML5.1) since the megathrust earthquake occurred on 31 March 2014 in the Yellow Sea. An ML5.0 earthquake occurred in a region off the southeastern coast on 5 June 2016. Midcrustal ML 5.1 and 5.8 earthquakes occurred within a time interval of 48 min on the southeastern Korean Peninsula on 12 September 201622. The ML5.8 earthquake was the largest event in the instrumental seismic monitoring history since 1978. The event occurred in a midcrustal blind fault22, and it released the stress of the fault to adjacent regions, producing aftershocks. The aftershocks occurred dominantly for more than 1 year in regions with positive Coulomb stress changes.The first ML5.4 earthquake occurred in a region of positive Coulomb stress changes by the 2016 ML5-level earthquakes22. The fault planes of the moderate-size events in 2016 and 2017 were not found on the surface. The 2016 and 2017 moderate-size earthquakes both produced strong seismic waves, presenting similar spatial distributions of ground motion over the Korean Peninsula  midcrustal earthquakes on 12 September 2016 perturbed the local stress field significantly22. Earthquakes started to occur in the regions of positive Coulomb stress changes induced by the 2016 moderate-size earthquakes .We investigate the properties of time-advanced earthquakes in a stable intraplate region from the three inland ML5.4 earthquake region was seismically quiescent before the 2011 Tohoku-Oki megathrust earthquake . Note that no events with magnitudes greater than or equal to 2.0 were reported in the epicenter region with a radius of 10 km before the 2016 ML5-level earthquakes. Four earthquakes with magnitudes greater than or equal to 2.0  occurred around the epicentral region with a radius of 3 km since the 2016 ML5-level earthquakes.The 2017 ML5.4 earthquake was 1.85 × 1017 Nm, and the corresponding moment magnitude was Mw5.5 . The strike of the fault was N45°E, and the dip was 61° to the west. The fault for the 2016 ML5.8 earthquake presented a strike of N27°E and dip of 65° to the east22. The refined focal depth of the 2017 ML 5.4 earthquake was 6.2 km. The earthquake showed a combined motion sense of reverse and strike-slip faulting  on the Korean Peninsula28.The aftershock occurrence rate of the 2017 ML5.4 earthquake was rich in low frequencies around ~0.5 Hz compared to that from the 2016 ML5.8 earthquake  of the 2017 ML5.4 earthquake was similar to that of the 2016 ML5.8 earthquake  of the southeastern Korean Peninsula. The epicenter region of the 2017 ML5-level earthquakes in 2016 and 2017 were not recognized before their occurrence. The 2016 ML5.1 and 5.8 earthquakes occurred in a strike-slip fault at depths between 11 and 16 km22. The dip of the fault was ~65° to the east. Additionally, the 2017 ML5.4 earthquake occurred in a blind crustal fault . This observation suggests that the mainshock and aftershocks occurred under a constant stress environment.The mainshock occurred at the boundary between the southwestern and central segments. The early sequence of aftershocks was located mainly in the southwestern segment, accompanying some aftershocks in the northeastern segment. Most of the aftershocks in the northeastern segment started to occur 2 hours after the mainshock . The later sequence of aftershocks was clustered around the central segment, which is located less than 2 km to the north of the mainshock. The earthquake migration suggests time-dependent faulting. Furthermore, the compression-axis directions of the 2017 The lateral distributions of aftershocks in the southwestern and northeastern segments are consistent with the strike of the mainshock. The fault plane in the southwestern segment dips to the NW at an angle of 61° from the surface. The fault plane of the northeastern segment developed at depths between 5.0 and 7.2 km. The dipping angle was 84°. The southwestern segment is connected to the northeastern segment by the central segment. The central segment plays the role of conjunction between the southwestern and northeastern segments. The reverse-faulting in the central segment may have been caused by lateral-stepwise motions of the northeastern and southwestern segments at different depths, inducing a vertical dislocation in the central segment Fig. .12.The crust of the Korean Peninsula was stretched by the differential coseismic and postseismic displacements due to the 2011 Tohoku-Oki megathrust earthquake, reducing the yield strengths in the crustML5.1 and ML5.8 earthquakes produced Coulomb stress changes of −4.9 to 2.5 bar for optimally oriented strike-slip faults at a depth of 10 km  . We found that the induced Coulomb stress change for the 2016 ML5.1 and ML5.8 earthquakes for the illuminated fault geometry of the 2017 ML5.4 earthquake was 0.2 × 10−2 bar at the hypocenter of the 2017 ML5.4 earthquake. The increased stress at the 2017 ML5.4 earthquake region was sufficiently larger than the critical stress change level (~1 × 10−4 bar) required to trigger earthquakes30.The 2016 ML2.0 occurred in the region around the 2017 ML5.4 earthquake before the occurrence of the 2016 ML5.1 and ML5.8 earthquakes . The 2016 ML5.1 and ML5.8 earthquakes appeared to be the primary source of stress changes in the region of the 2017 ML5.4 earthquake. The 2017 ML5.4 earthquake occurred in a region of increased stress caused by the 2016 ML5.1 and ML5.8 earthquakes.No earthquakes with magnitudes greater than ML5.4 earthquake caused additional stress changes, building a complex stress field around the southeastern Korean Peninsula  is the observed seismicity rate density at time t at location x, λ0(x) is the background intensity function, and λi is the contribution of earthquake i that occurred in time ti at location xi. We decluster the earthquake catalog based on a nonparametric method that is useful for regions with low seismicity rates. The functions λi and λ0(x) are determined by an iterative process that assesses the numbers of event pairs in discrete bins of magnitudes, interevent times and distances39 .The observed seismicity can be expressed as a sum of background seismicity and triggered seismicity40 based on a global-averaged one-dimensional (1-D) velocity model41. We determine a set of hypocentral parameters that generate the best-fit synthetic waveforms42. The focal mechanism solutions of the earthquakes are determined based on 5 seismic records of 0.05–0.1 Hz in regional distance 44. This method is effective for the determination of hypocentral parameters of earthquakes in media with poorly known velocity structures . We implement a 1-D velocity model as the initial model45. We analyze 14 to 34 three-component waveforms of each earthquake for the hypocentral-parameter inversion. The average P and S travel time residuals are 6.1 × 10−6 s and 4.9 × 10−3 s, and their standard deviations are 0.0489 s and 0.1948 s, respectively . The horizontal and vertical location errors at the 95% confidence level are 9.7 m and 24.3 m. The origin time and hypocenter errors are sufficiently small.The hypocentral parameters of the earthquakes are refined using VELHYPO based on the 47τ is the shear stress change, μ′ is the effective frictional coefficient, and Δσn is the normal stress change. We set the effective frictional coefficient μ′ to be 0.448. The fault dimension is assumed to follow an empirical relationship with the seismic moment49. The ambient compressional stress field is oriented in the N77°E direction, with a strength of 65 bars22 (Fig. 47. The Coulomb stress changes induced by the earthquakes are calculated for media with strike-slip faults in the optimal orientation or given orientation50.The induced Coulomb stress change, ΔCFS can be represented bymentclass2pt{minimSupplementary materials


The psychological consequences of infertility in couples undergoing oocyte donation differ culturally, racially, religiously, and legally from other infertile couples undergoing assisted reproductive treatments. Therefore, the inclusion of a mental health program in assisted reproductive services is essential for these couples. As such, the aim of this study is to develop a program for improving the mental health of these couples.This study is designed using an exploratory mixed method and the program based on Talbot and Verrinder model. Different steps of this research include determination of a specific topic for planning (needs assessment), initial design of the program, finalization of the program (using the views of experts in this area), implementation of the program, monitoring of the implementation of the program and evaluation of the program. To perform the first step of Talbot’s program, the first phase of the study will be conducted. At first, through a qualitative study, the items of the questionnaire are designed and then its psychometric steps will be performed by a cross-sectional study. In the second and third steps, the classic Delphi technique will be used in four-round for initiation and finalization of the program, and the second phase will be completed. The fourth, fifth and sixth steps of the program including implementation, monitoring of the implementation and evaluation of the program in the future will be performed.Designing an appropriate program based on the documentations of the qualitative study and evidence can improve the mental health and quality of life of the couples undergoing oocyte donation. The program, based on the measurement of needs, will be implemented using a tool designed specifically for the target population and can be useful in the processes of treatment, education, policymaking and legislation as well as research. Studies have shown that among needs, emotional and psychological needs are the most important ones. According to the evidence, infertility-related psychological problems, including stress and anxiety, can be a contributing factor to the exacerbation of infertility and failure in the process of its treatment. The psychological consequences of infertility in couples undergoing oocyte donation differ culturally, racially, religiously, and legally from other infertile couples undergoing assisted reproductive treatments. Therefore, the inclusion of a mental health program in assisted reproductive services is essential for these couples. As such, the aim of this study is to develop a program for improving the mental health of these couple. This study is designed using an exploratory mixed method based on Talbot and Verrinder model. Different steps of this research include determination of a specific topic for planning, initial design of the program, finalization of the program (using the views of experts in this area), implementation of the program, monitoring of the implementation of the program and evaluation of the program. To perform the first step of Talbot’s program, the first phase of the study will be conducted. At first, through a qualitative study, the items of the questionnaire are designed and then its psychometric steps will be performed by a cross-sectional study. In the second and third steps, the classic Delphi technique will be used in four-round for initiation and finalization of the program, and the second phase will be completed. The fourth fifth and sixth steps of the program including implementation, monitoring of the implementation and evaluation of the program in the future will be performed. The integration of a mental health program specific for this group of infertile couples into the care program of this group can bring about significant result.Infertility is one of the public health problems in the world that can threaten individual, marital, and social balance; because infertility is an unexpected tension and severe stigma for infertile couples  that canDespite the therapeutic benefits and successes, the use of donated oocyte can cause challenges and harms for couples. The health of the donor, the quality of the donated oocyte, the potential for transmission of inherited diseases through donation , religioSuch challenges in this treatment method can differentiate the consequences of infertility in these couples from other infertile couples and consequently, create different needs including different psychological needs in these couples. Accordingly, couples using donated oocytes often expect to receive comprehensive and high quality care and treatment, and special attention should be paid to their mental health. The reason is that discovering the needs and priorities of clients in the infertility process , 17 and Mental health, as one of the most important aspects of health, can affect other aspects of one’s life including quality of life . AccordiDespite the need to provide these infertile couples with mental health services, no special mental health program has been developed for these couples. Therefore, this study aims to develop a program based on the specific needs of couples using donated oocyte.This multi-level research, approved by the Ethics Committee of Isfahan University of Medical Sciences in Isfahan, Iran (IR.MUI.RESEARCH.REC.1398.312) will be conducted to develop a program for promotion of the mental health of infertile couples undergoing assisted reproductive treatment using donated oocyte. Informed consent will be obtained from all participants at all phases of the research. The development of this program will be based on the Talbot and Verrinder model, and include the following steps: determination of a specific topic for planning, initial design of the program, finalization of the program (using the views of experts in this area), implementation of the program, monitoring of the implementation of the program and evaluation of the program .This research will be performed in three phases. In the first phase, the psychological needs of the couples will be identified using an exploratory mixed method. In the second phase, the program will be designed and validated based on the results of the first phase. In the third phase, a pilot study is designed to evaluate the impact of the program and its future implementation.This phase consists of a two-stage exploratory mixed study , the first stage of which covers Talbot program to determine the specific topic for planning. In the qualitative part, the psychological needs of the couples undergoing assisted reproductive method of oocyte donation are extracted. In addition, at this stage, the items of the tool for measuring these needs will be formulated based on the findings of the qualitative study. Then, using a cross-sectional study on the target population, the psychometric steps of the tool will be done and the level of psychological needs is also assessed.In the qualitative study, the psychological needs of these couples are identified by conducting unstructured interviews and audio recordings. Purposive sampling method will be used at this stage. Iranian infertile couples undergoing assisted reproductive treatment using oocytes donation referring to infertility centers in Isfahan, Iran as well as health care providers will be used for gaining more comprehensive information. The aim of the study, the reason for the recording of the interview, the voluntary participation, the confidentiality of the information and the identity of the interviewee will be explained.Inclusion criteria for couples using oocyte donation will be the ability to communicate appropriately, the ability to provide rich and complete information, and not suffering from any severe and persistent mental illness according to a psychiatrist and case documentation. Inclusion criteria for the personnel of the infertility centers will be willingness to participate in interviews. The unwillingness to continue their cooperation at any stage of the research and for any reason is considered as the exclusion criterion for each sample. At this stage, data are collected through open and unstructured interviews as well as on-site note taking. Informed consent will be obtained from the participants for recording the interviews, and the time, length and location of the interview will be chosen based on the participant’s preference. Interviews will be analyzed using the content analysis method (Granheim-Lundman method). Furthermore, based on the results of this stage, the items for measuring the psychological needs of the couple (PNS) will be designed.To assure accuracy and reliability of the data, the four criteria of credibility, dependability, confirmability, and transferability will be used.PNS questionnaire will be a self-report questionnaire with a five-point Likert scale (0–4) that is psychometrically assessed according to standard procedures.The face validity of the questionnaire will be measured both qualitatively and quantitatively. To evaluate the face validity of the questionnaire qualitatively, all items will be evaluated for clarity, understanding, and simplicity by a number of members of the target group and providers infertility services to them, as well as a five-member team consisting of a psychiatrist, psychiatric nurse, and reproductive health specialist. The face validity will also be measured quantitatively by using the quantitative method of item impact. To this end, a 5-point Likert tool will be used in which the scores are assigned as “quite important” (5 points), “somewhat important” (score 4), “moderately important” (score 3), “slightly important” (score 2) and “not important” (score 1). Any item scored greater than 1.5 will be a good item and will be retained for later analysis.To determine content validity qualitatively, the opinions of the experts  will be used. Content validity ratio (CVR) and content validity index (CVI) will be used to evaluate content validity quantitatively.To determine the content validity ratio (CVR), each of the items of the questionnaire is judged by the experts in terms of necessity. The researcher will give the questionnaire to the experts and ask them to judge the items using the three-part scale of 1) “the item is necessary,” 2) the item is useful but not necessary,“ and 3) the item is not necessary”. The content validity ratio is then calculated using Lawshe formula. Based on Lawshe table, if the number of specialists is 10, the minimum acceptable value for CVR is 0.62. Accordingly, items whose CVR is above 0.62, will be retained . To measThe quantitative phase of this study is a cross-sectional study conducted on a number of infertile couples undergoing assisted reproductive treatment of oocyte donation. The sample size will be determined using the law of the ratio of the items to the respondents that equals 3 to 4 subjects per item and can be up to 10 subjects per item . InclusiExploratory factor analysis is used to determine the construct validity using SPSS18 software. Moreover, confirmatory factor analysis will be performed using the AMOS18 web software.For the evaluation of criterion validity, the General Health Questionnaire-28 (GHQ-28) introduced by Goldberg and Hillier will be used . This quTo determine internal consistency in this study, Cronbach’s alpha coefficient will be used for the whole tool, and factor analysis with the same samples of factor analysis stage for each factor separately. The stability in this study will be evaluated using a test re-test method on 10% of the participants of the cross-sectional study. Then, the score of the validated questionnaire and the criterion validity score are compared with the general health questionnaire and, finally, the psychological needs of these couples are determined using the developed tool.Development and evaluation of a program to address defined mental health problems and improve mental health in this specific group.Design a program appropriate for the specific needs of these clientsDesign a program with the ability to solve mental health problems in the simplest and most effective way.Accordingly, the action plans of the program will be designed using appropriate models.In order to initialize and finalize the program , an initial draft of the mental health program is prepared using the findings of the previous phase. Overall goals, specific goals, suggested strategies, and activities required for the mental health of couples undergoing oocyte donation will be developed. The focus of the program will be on the factors identified in the first phase of the research as the most important factors related to mental health. The following features will be considered in the design of the program:Validation and finalization of the program is done using classic Delphi technique in four rounds and according to the priorities and goals of the program. The members will be used purposive sampling method. The panel members will consist of 10 experts . Inclusion criteria of the panel participants: their scientific knowledge in the area of research and having at least 2 years of care providing in ART center. Exclusion criteria: their unwillingness to continue their cooperation in the research.In the first round, the initial version of the program is prepared and, along with open-ended questions, will be presented to experts, and they are asked to comment on issues such as ease of implementation, cost effectiveness and the time required for implementation. After collecting the returned copies, they are organized and the structured questionnaire is used as the tool of the second-round. In the second round, the members are asked to rate and quantify the program items using a Likert scale. The analysis is then performed as a content analysis and, applying the comments of the experts, the revised version together with the evaluation checklist is provided to the experts, and then the revised program (the third version) is given to them. The strengths and weaknesses of the program are identified in this round, and the comments will be revised if needed. In the fourth round of the program, rankings, minority opinions and consensus items will be distributed among the panelists and the final program will be approved.The fourth, fifth and sixth steps of the Talbot model are implementation, Monitoring of the implementation and evaluation of the program will be supervised. Owing to budget constraints, the program will not enter the pilot phase, but will be provided to the Isfahan Infertility Center for pilot, implementation and impact assessment.The aim of this study is to develop a mental health promotion program for couples using donated oocytes. According to a logical premise, people are the best source for describing their own situation, needs, feelings, and experiences by their own words  ThereforHowever, differences in the disparate socio-cultural context of other countries may limit the application of this program elsewhere. Furthermore, lack of evaluation of the impact of the program on couples’ mental health, because of the project’s financial constraints, is one of the limitations of this study.


BCR-ABL1 fusion protein, encoded by the Philadelphia chromosome, have drastically improved the outcomes for patients with chronic myeloid leukemia (CML). Although several real-time quantitative polymerase chain reaction (RQ-PCR) kits for the detection of BCR-ABL1 transcripts are commercially available, their accuracy and efficiency in laboratory practice require reevaluation. We have developed a new in-house RQ-PCR method to detect minimal residual disease (MRD) in CML cases. MRD was analyzed in 102 patients with CML from the DOMEST study, a clinical trial to study the rationale for imatinib mesylate discontinuation in Japan. The BCR-ABL1/ABL1 ratio was evaluated using the international standard (IS) ratio, where IS < 0.1% was defined as a major molecular response. At enrollment, BCR-ABL1 transcripts were undetectable in all samples using a widely-applied RQ-PCR method performed in the commercial laboratory, BML ; however, the in-house method detected the BCR-ABL1 transcripts in five samples (5%) (mean IS ratio: 0.0062 ± 0.0010%). After discontinuation of imatinib, BCR-ABL1 transcripts were detected using the in-house RQ-PCR in 21 patients (21%) that were not positive using the BML method. Nineteen samples were also tested using a commercially available RQ-PCR assay kit with a detection limit of IS ratio, 0.0032 . This method detected low levels of BCR-ABL1 transcripts in 14 samples (74%), but scored negative for five samples (26%) that were positive using the in-house method. From the perspective of the in-house RQ-PCR method, number of patients confirmed loss of MMR was 4. These data suggest that our new in-house RQ-PCR method is effective for monitoring MRD in CML.Tyrosine kinase inhibitors (TKIs) targeting the  BCR-ABL1 fusion transcripts. The BCR-ABL1 protein constitutively activates tyrosine kinase (TK)  that is different from the one used in this study. Although the detection limit of ODK-1201 was claimed to be 00007%, the IS% BCR-ABL1/ABL1 obtained from the 154 samples from CML patients fell into between 0.0014% and 144.6867%. The IS% below the detection limit obtained from CML patients (70 samples), 21 non-CML patients and 25 healthy subjects were represented as 0.0001% [BCR-ABL1 transcripts were supposed to be very low, and we could compare only 19 samples due to sample availability. Taking these facts together, the discordance between these two methods may not be surprised when such small amount of RNA molecule(s) are measured.In the DOMEST trial, clinical decisions were made based on the monitoring of ML Inc.) . The BCR15 cases . By cont15 cases . Althoug 0.0001% . This ma 0.0001% , which iBCR-ABL1 fusion transcripts has been claimed as 5 logs [BCR-ABL1 fusion transcripts requires further improvement.In recent clinical trials to evaluate the rationale for TKI cessation, the sensitivity of assays used for detection of s 5 logs , 31; hows 5 logs . TherefoThis study has certain limitations. The clinical relevance of our new in-house RQ-PCR is uncertain since it has not been assessed in large-scale randomized clinical trials. Moreover, very long-term outcomes of imatinib therapy in CML have yet to be elucidated . CurrentIn conclusion, our newly developed in-house RQ-PCR method with IS calibration was accurate and effective for detecting MRD in the context of an imatinib cessation study. The main advantages of this assay lie in the promptness with which results are obtained and its ease of use. Thus, this method could be advantageous for implementation in hospital laboratories, where small numbers of samples are tested.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S1 Fig(TIF)Click here for additional data file.