This article presents the impact on cyberbullying of the Asegúrate program. This educational program is based on the theory of normative social behavior, self-regulation skills, and the beliefs held by adolescents and consists in a whole package of strategies and resources to help teachers to include in the ordinary curricula. The evaluation of Asegúrate was carried out with a sample of 4779 students (48.9% girls) in 5th and 6th grade in primary education and compulsory secondary education  through a quasi-experimental methodology, with two measures over time. The instrument used was the European Cyberbullying Intervention Project Questionnaire. The results show that the involvement in cyberbullying as cyber-victim, cyber-aggressor, and cyber-bully-victim increase without intervention, whereas it diminishes when intervention is carried out by the teachers who have received specific training and have used the didactic Asegúrate package. Additionally, the impact of the intervention on the different types of behaviors was analyzed, and the results show that Asegúrate is more effective with some forms than with others. Consequently, the Asegúrate program is effective for decreasing the prevalence of cyberbullying, but some modifications need to be made to impact on all the different forms it can take.  In recent years, there has been increased awareness among both teachers and school counsellors that interpersonal relationships between pupils, and the classroom atmosphere in general, are complex processes that are heavily influenced by the social microculture of that particular school and the educational and the pedagogical style of the teaching staff . Until tHowever, since the arrival of internet and, above all, mobile digital technology and social networks accessed via smartphones, social interaction among children and adolescents has become far more complex . DespiteCyberbullying has been studied from a number of different angles , but theThe prevalence rates of cyberbullying vary considerably from one study to another . AccordiThis scientific evidence about the existence and consequences of cyberbullying, together with alarming stories of cyber-victims, which appear in the media and its close links with traditional bullying ,28,29 haIt has been shown that the teaching staff play a vital role in the effective implementation of programs against traditional bullying , and theUnlike other research projects in which teaching staff have been trained intensively or extensively to participate in implementing programs against cyberbullying , the AseThe Asegúrate program rests on three theoretical pillars: the theory of normative social behavior, the principles of constructivist methodologies, and the development of self-regulation skills. The first of these highlights how social behavior is significantly influenced by three normative mechanisms: group identity, expectations, and recognized legal norms. It upholds the notion that our behavior is likely driven by what is perceived as socially acceptable, normal, and legal ,44. The The complete program consists of eight sessions on cyberbullying and other related factors, including the ways people communicate on social networks and their implications; anomalies in online behavior; criteria for establishing safe online friendships; cybergossip; sexting; the abuse of the Internet and social networks, and the norms of cyber-etiquette. Detailed instructions are given as to how to conduct the tasks for each of the eight sessions in the program. Each session contains a specific activity that ensures that the requirements of the Asegúrate methodology are fully complied with. Each teacher is therefore given a full description of the steps to follow with their pupils, and extra resources and explanations are included. Finally, there is a self-access reference section including a glossary of terms, a resource bank (such as descriptions of the most popular YouTubers), links to further reading, etc. Another section provides the answer keys and instructions for evaluating each session and the Asegúrate program as a whole. Apart from the manual, the Asegúrate program also features audio-visual material for each of the sessions for teachers to use with the pupils and their families, as well as awareness-raising publicity resources such as posters, stickers, or bookmarks. The idea is for the teachers to use this complete range of resources to help them tackle the problem of cyberbullying with their pupils.The Teacher’s Manual fulfils the basic requirements as a useful teaching guide for professional adults to learn autonomously and provides both general guidelines and detailed procedures, including thorough instructions for the tasks and roles, self-help, and specifically targeted orientation . The oriTaking all of the above into account, the aim of this study was to evaluate the effectiveness of the Asegúrate program in counterbalancing, through education, the involvement of schoolchildren in cyberbullying, whether in the roles of victim, aggressor, or in the dual role of cyberbully/victim, as well as stemming the increase in cyber-victimization and cyber-aggression both in general and specific cases of aggression.This study has a longitudinal, quasi-experimental design. There are two study groups—a quasi-experimental group and a quasi-control group—and two data collection points—a pre-test before the program and a post-test at the end of the program.A total of 4779 pupils (48.9% girls) took part in this study, from the 5th year of Spanish primary education (average age: 10–11) to the 4th year of Spanish secondary education (average age: 15–16 or higher), from 18 different schools. The ages ranged from 10 to 18 years old . The experimental group consisted of 2316 pupils (50.4% girls) from 18 schools, and the control group contained 2463 pupils (47.5% girls) from 10 schools. The sampling was incidental: access was through invitations issued to schools to participate in the program, and the schools could agree whether to accept or not.Someone has posted threatening messages against me on Internet, social networks, or WhatsApp. Examples for cyberbullying included the following: I have insulted someone through social networks or WhatsApp. The reliability of the scale for the present study was α = 0.80 (α = 0.76 for cyber-victimization and α = 0.73 for cyberbullying).The European Cyberbullying Intervention Project Questionnaire (ECIPQ) was used to assess the level of involvement in cyberbullying . This scThe schools were contacted by phone and asked if they would like to take part in the study. An appointment was arranged for those schools which agreed, and the schedules and the classes which would participate in the study were decided. With the agreement of the teaching staff, the questionnaires were administered during class time by staff in training, who were specially instructed for this task. Before answering the questionnaires, the participants were fully briefed about the voluntary nature of participating in the study, the anonymity and confidentiality of the data, and the importance of giving truthful answers.After the data was collected in February 2017, the Asegúrate program was carried out in the quasi-experimental groups, but not in the control groups. After the program was completed, the questionnaires were repeated, at least three months after they were first answered, June 2017 at the latest. Those schools where the program was not carried out were offered the chance to take part in it once the study was completed.The research was carried out following the ethical standards agreed on by each schools’ Parents’ Association, and was approved by the Andalusia Biomedical Research Ethics Coordination Committee (0568-N-14), which adheres to the guidelines of the International Conference of Good Clinical Practice. All the materials and questionnaires that made up the project were presented and explained to the school management, which gave it their approval in all cases. They, in turn, discussed it with the School Council, as part of the schools’ Projects for Peaceful Coexistence and School Improvement Plans; again, full approval was given for the schools to take part in the study.once or twice a month” or more to any of the questions about victimization behavior and simultaneously answered “no” or “once or twice” to questions regarding all behavior related to aggression. To calculate the level of aggression, pupils were considered “bullies” if they stated that they had harassed someone “once or twice a month” or “more frequently” for any type of behavior classed as cyberbullying and simultaneously answered “no” or “once or twice” for types of behavior linked to cyber-victimization. In the same way, pupils were labeled “bully/victims” if they answered “once or twice a month” or more for behavior linked to victimization and aggression.The first step in analyzing the results of this research was to check the response frequencies for the different types of behavior evaluated by the questionnaire. Next, the prevalence of involvement was calculated following the criteria proposed by the authors of the scales used : pupils The percentage variation was then calculated for each of the groups . This variation shows the difference in prevalence between the values shown in the pre-test and those in the post-test. The following formula was used to calculate this variation: [/PrevalenceT1] × 100.Finally, to evaluate the effectiveness of the program for the different types of behavior in the study, the linear mixed model or repeated measures MANOVA was calculated.Firstly, the descriptive results were calculated by examining the frequency of responses in both groups  for the different types of behavior measured by the questionnaire, in order to evaluate involvement in cyberbullying in the pre-test see . The mosNext, we calculated the percentages of involvement in the different roles of cyberbullying , for both the experimental and control groups at both the pre-test and post-test stages see . Here, t = 12.63, p < 0.01, d = 0.29). The same pattern could be observed for the level of aggression, where the control group score remained the same, while there was a significant fall in the score in the experimental group after the program was carried out = 6.66, p < 0.01, d = 0.25).Finally, the repeated measures MANOVA was calculated for each of the 11 items of victimization and aggressive behavior measured in the cyberbullying questionnaire at the two stages when these were carried out see . These r = 4.05, p < 0.05, d = 0.20), posting insults about the victim  = 5.16, p < 0.05, d = 0.21), threats  = 5.25, p < 0.05, d = 0.21), exclusion  = 15.75, p < 0.01, d = 0.30), and spreading rumors  = 9.42, p < 0.01, d = 0.25) decreased clearly in the experimental group compared to the control group, which showed either no changes or a slight fall.As regards the specific behavior of victimization, after the program was carried out, direct insults  = 14.66, p < 0.01, d = 0.30), threats  = 5.87, p < 0.01, d = 0.22), and exclusion  = 7.21, p < 0.01, d = 0.23) decreased significantly in the experimental group compared to the control group, which saw hardly any changes or even a slight increase.As regards aggressive behavior, the scores for insults  to use autonomously. This educational material focuses on cyberbullying and on the social behavior teenage boys and girls display online when using virtual social networks. The Asegúrate program assumes that teachers are sufficiently aware that this behavior can disrupt the social climate and well-being of their pupils and that they will carry out self-training and acquire suitable levels of professional competence to intervene when such behavior occurs. We also assumed that, if teachers increased their competence in this way by using the materials available to them including the Asegúrate manual, then the levels of cyberbullying in the classroom would improve, as measured by self-administered questionnaires given to the schoolchildren themselves, as is the norm in studies of bullying and cyberbullying . This syThis has allowed us to observe that verbal cyberbullying, which is close to traditional forms of bullying, such as insults, threats, social exclusion, and spreading rumors, is the most frequent type in both groups, both in victimization and aggression: in other words, the commonest form of cyberbullying is still very similar to traditional bullying. By this, we can deduce that the new forms of cyberbullying introduced by technology, such as identity theft or manipulating multimedia, images, or videos with the intention of offending or hurting the victim, are less widespread among the adolescent population, at least in the cross section of pupils who participated in this study. These results also seem to show that the main aspect that is transferred to the online context is traditional aggressive behavior, to a far greater degree than the actual use of technology. We feel this is a relevant discovery, since it supports the idea that rather than the digital platforms opening the floodgates to new kinds of bullying , cyberbuIn addition, the secondary objective of this work was to evaluate the effectiveness and suitability of the self-training manuals written by our scientific team and made available to the teachers who took part in the study  to use as they saw fit. The Asegúrate teaching manual, interpreted and used autonomously by teachers in the schools involved in the study, has led to significant changes in the pupils’ involvement in the program. The experimental group obtained extremely positive results in improving the situation regarding victimization, aggression, and the number of bully/victims. Some improvement was also noted in the control schools, but to a lesser extent than in those involved in the experiment. The most notable result was the clear decrease in victimization, aggression, and bully/victims in the experimental group, compared to the very slight fall for the control group in victims and aggressors and the sharp rise in bully/victims . If thesThe role of bully/victim, in which pupils are not only victimized by their peers, but are also aggressors at the same time, has been described as one which involves far greater problems of psychological adjustment . AlthougWhen both experiences decrease (cyber-victimization and cyberbullying), the involvement of teachers can become an extremely relevant factor for change, since the phenomenon of cyberbullying is mutualistic, in that bullying is both given and received. Teachers who make it a priority in the course of their professional activity to focus on specific problems of bullying and deal with them effectively, guided by their own convictions, appear to exercise a strong influence against the spread of cyberbullying . The AseAfter the initial self-training, the teaching staff who put the Asegúrate program into practice made special efforts to combine activities specially designed by experts with their own interpretation and self-planned techniques, which they adapted to the social context of their own pupils. This illustrates the importance of the teaching staff as a key element in the intervention against cyberbullying . Just asThe Asegúrate program has been effective against all the types of behavior, which are associated with involvement in cyberbullying, which represents such a problematic phenomenon for schools. In fact, the indicators which show a reduction of involvement in both roles reveal highly significant changes. Not only does the specific behavior of cyberbullying and cyber-victimization decrease, but also a large number of the boys and girls who were previously noted as “involved in cyberbullying phenomena” in the pre-test were classified in the post-test in the “not-involved” or “bystanders” group. In fact, there was a significant increase in the number of “bystanders” in the post-test in the experimental group compared with the control group, with around a 25% decrease in the number of cyber-victims and a fall of over 30% in the number of cyberbullies.It should also be noted that the evaluation of the Asegúrate program has certain limitations. The use of self-reports has its obvious shortcomings, but perhaps the most relevant is that the Asegúrate program could be improved further with more specific training to deal with the specific behavior of schoolchildren when using digital devices. Although this type of behavior does not appear to be extremely widespread, the harmful, dangerous behavior it involves did not decrease in adolescents even after the program was carried out. It therefore seems essential to include a study of the dynamics of how adolescents use digital devices, as well as materials and training to help make the program more effective in this respect. Likewise, other variables that are impossible to measure in this type of research could be related to the changes found in other activities in the school, additional teacher training, etc.The results we obtained are in line with the different articles in the scientific literature about the prevention of cyberbullying, which show that the teaching staff are one of the key factors in reducing and alleviating the problem ,20,59. HAlthough cyberbullying occurs in a virtual environment, where some teachers feel less comfortable or reluctant to explore because of their lack of prior experience , our resFor this reason, our results emphasize that it is not essential that teachers immerse themselves or have an expert domain of virtual environments, social networks, or cross-platform applications to improve how their students behave online. The useful work that has been carried out over a long period of time against traditional harassment , which p


The VA Geriatric Scholars Program is a workforce development program to integrate geriatrics into primary care in all VA clinics. The program has increased career satisfaction among clinicians, improved quality of care for aging Veterans, changed provider prescribing behaviors and improved patient outcomes. The core curriculum is an intensive course in geriatrics, an intensive workshop in quality improvement (QI) and a micro QI project to demonstrate application of new knowledge to local needs of patients and clinic processes; this is a longitudinal program and alumni continue to develop skills over time through a series of elective activities that tailor learning to self-identified gaps in career development and training. The program is a collaboration among the Geriatric Research Education and Clinical Centers (GRECC), centers of excellence that have been leveraged to create a network of expertise and creativity to develop the core and elective educational activities. This symposium focuses on recent outcomes of three educational components that improve quality of care for older Veterans. The Palo Alto GRECC developed an intensive course in gerontological psychology to enhance the skills and competencies of psychologists leading to greater job effectiveness. The Bronx GRECC developed an interdisciplinary training program for all clinical and non-clinical staff in rural clinics, leading to improved recognition of functional and safety concerns among older veterans. The Tennessee Valley GRECC developed the core QI component and many of these micro-QI projects have been sustained, spread or recognized by VA as Promising Practices.


In a rapidly aging society, like that in Japan, it is imperative to establish strategies to prevent dementia. We investigated the effects of a dementia prevention program, conducted as part of a municipality’s long-term care prevention project, on cognitive/motor functions among the community-dwelling elderly. Participants underwent a physical activity program involving muscle training and aerobic exercise, once a week, for 12 weeks. Cognitive and motor tests were performed twice, before and after the intervention. Thirty participants, aged 75.7 ± 6.7 years, were included in the analysis. Scores from the immediate word memory task were significantly increased (23.0 ± 7.8 vs. 25.7 ± 6.5) after the program. Scores from the Yamaguchi Kanji Symbol Substitution Test were also significantly increased (36.2 ± 13.1 vs. 40.1 ± 14.1). Time spent during the 5 m maximum walking speed test was significantly shorter after the program (3.4 ± 0.8 vs. 3.0 ± 0.7 s), whereas the daily walking distance increased significantly (1.9 ± 1.5 vs. 3.1 ± 2.2 km). Participants showed improvement in some aspects of their cognitive/motor function and walking distance per day. Therefore, this program can be regarded as a practical community-based healthcare activity. In a rapidly aging society, like that in Japan, the number of elderly with dementia is expected to increase annually . TherefoThe “Basic Guidelines for the Promotion of Community Healthcare Measures” issued by the Ministry of Health, Labour and Welfare of Japan (MHLW) recommends volunteer work led by community residents and in-group activities to promote community healthcare . MunicipIn 2006, the LTC insurance system of Japan was revised to place more importance on the prevention of dementia, along with the establishment of LTC prevention projects targeting the community-dwelling elderly ,6. TheseRecent epidemiological research has suggested that regular physical activity, which helps to prevent cognitive decline among the elderly, contributes to a decreased incidence of dementia ,9,10,11.The aims of this study were to investigate the effects of a dementia prevention program on the cognitive and motor functions of the community-dwelling elderly and to determine whether this program helps them develop exercise habits.The Isesaki City Community General Support Center sent the basic checklist by mail to 38,018 individuals aged ≥65 years who had not been certified as requiring support or nursing care as of May 2014. A total of 26,584 completed the checklists, which were then collected . Based upon the responses received, 7198 elderly people were selected as requiring secondary prevention services. Among these individuals, 1680, living in the three districts in which dementia prevention programs were planned, received a brochure announcing the program by mail. Of the 32 individuals who wished to attend the program, 31 consented to participate in our study. All participants, except the one who withdrew from the study because of an injury, attended eight or more of the 12 program sessions. Consequently, a total of 30 elderly people were analyzed. The medical ethics committee of Gunma University approved this study , and written informed consent was obtained from all participants.Before the initiation of the dementia prevention program, the public health nurses gave participants a self-completed questionnaire that inquired about the following items: subjective health status , walking habits , frequency of forgetfulness , degree of forgetfulness , and functional activities, which were assessed using the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC) . The subDuring the baseline evaluation, public health nurses assessed the participants’ general cognitive function using the Mini Mental State Examination (MMSE) . The othA 5 m maximum walking speed test and timed up-and-go test (TUG) were performed to evaluate the physical function of each subject. Improvement is reflected by a decrease in the time required to complete the 5 m maximum walking speed test and TUG.During the second evaluation after finishing the program, a questionnaire survey, cognitive function tests other than MMSE, and physical function tests were performed.The dementia prevention program was implemented at a civic gymnasium once a week for 12 weeks. The mean duration of the program was 90 min. The physical activity program was the primary content of the program. The program included two types of muscle training exercises in a sitting position, two types of muscle training exercises in a standing position, and aerobic exercise. All these activities were performed under the direction of public health nurses. Participants were encouraged to perform the same activities, including walking, at their home daily. Pedometers were provided to the participants to record the number of steps taken each day.The staff of the dementia prevention program comprised six public health nurses from the Isesaki City Community General Support Center, one nurse, and one physical therapist. In August 2014, a volunteer training workshop was held for dementia supporters (trained and certified volunteers who help patients with dementia and their family caregivers) living in the city. Among the 30 workshop attendants, 19  desired to cooperate in the dementia prevention program. Three to seven dementia supporters attended each program session to support the participants and assist the professional staff.The program was conducted on the basis of the following five principles of brain-activating rehabilitation: (1) a comfortable atmosphere; (2) empathetic communication with each other; (3) praising each other; (4) having a social role; and (5) errorless learning . The heat-test was used when the values showed a normal distribution and the Wilcoxon signed-ranks test was used when the distribution was not normal. These analyses were performed using the Japanese version of SPSS version 21 . Differences resulting in p < 0.05 were regarded as significant. The effect size and power for the significant differences were calculated using G*power .We analyzed data from participants who had consented to cooperate in this study and participated in eight or more of the 12 program sessions, as well as both the baseline and second evaluations. To analyze the representative values obtained from the baseline and second evaluations, the paired The participants comprised eight men (26.7%) and 22 women (73.3%), with a mean age of 75.7 ± 6.7 years. The average rate of attending the 12 program sessions was 92.1%. The average MMSE score was 27.7 ± 1.8 .p = 0.004, effect size: 0.373, power: 0.516). The YKSST scores also increased significantly . The word recall test scores changed from 9.7 ± 2.7 to 10.7 ± 3.3, before and after the program, although the difference did not reach statistical significance (p = 0.104). There were no significant differences in the scores of the delayed word memory task before and after the program.p = 0.003, effect size: 0.530, power: 0.801), suggesting an increase in the participants’ walking speed. The number of steps taken during the 5 m maximum walking speed test did not change significantly. The time required to complete the TUG test changed from 7.9 ± 2.1 to 7.4 ± 1.4 s, before and after the program; however, the difference was marginal (p = 0.081).The time required to complete the 5 m maximum walking speed test was significantly shorter after the program . No significant differences were observed in the scores of the subjective health status, frequency of forgetfulness, degree of forgetfulness, TMIG-IC, or self-reported walking time per day.The participants’ daily walking distance became significantly longer after the program   and instCognitive frailty is proposed as a new clinical construct with coexisting physical frailty and cognitive impairment in nondemented older adults . ReversiRegular exercise is, to a certain extent, effective in inhibiting the onset of dementia ,11. The The beneficial effects of non-pharmacological therapy, including exercise programs, are effective based on the manner in which they are provided, rather than their content . Therefon = 30), and the study period was short (12 weeks). A longer-term follow-up of the participants should be conducted to evaluate whether the positive effects are long-lasting. The present intervention study involved only a single group. It is necessary to conduct a controlled trial to investigate the effects of the program. The physical activity programs implemented in this study have improved the immediate word memory task and YKSST scores. However, the scores of the delayed word memory task and word recall test did not improve. It is necessary to clarify how the physical activity programs positively impacts the cognitive function domain. Although the executive function of the participants improved, its influences on ADL and IADL was not evaluated. Instead, we measured TMIG-IC because dementia prevention programs aim to maintain the independence of the community-dwelling elderly. Therefore, it is necessary to include the outcome measures of the abilities of participants to perform ADL and IADL in future studies.However, the present study has several limitations. The study participants desired to attend the program; therefore, these individuals may be more health-conscious than others. Changes in functional activities among the participants could not be accurately evaluated because of the ceiling effect of TMIG-IC. The number of participants involved was small (Participants in a municipality-implemented dementia prevention program based on exercise and supported by local dementia supporters showed improvement in some aspects of their cognitive and physical functions. Thus, the program can be regarded as a practical community-based healthcare activity and a primary dementia prevention program based on a population strategy.


MR level determination is dependent on the sensitivity of the monitoring technique. Here, we compared a newly established TaqMan (TM) and our so far routinely used LightCycler (LC) quantitative reverse transcription (qRT)-PCR systems for their ability to achieve the best possible sensitivity in BCR-ABL1 monitoring. We have comparatively analyzed RNA samples from peripheral blood mononuclear cells of 92 randomly chosen patients with CML resembling major molecular remission (MMR) or better and of 128 CML patients after treatment cessation . While our LC system utilized ABL1, the TM system is based on GUSB as reference gene. We observed 99% concordance with respect to achievement of MMR. However, we found that 34 of the 92 patients monitored by TM/GUSB were re-classified to the next inferior MR log level, especially when LC/ABL1-based results were borderline to thresholds. Thirteen patients BCR-ABL1 negative in LC/ABL1 became positive after TM/GUSB analysis. In the 128 patients included in the EURO-SKI trial identical molecular findings were achieved for 114 patients. However, 14 patients were re-classified to the next inferior log-level by the TM/GUSB combination. Eight of these patients relapsed after treatment cessation; two of them were re-classified from MR4 to MMR and therefore did not meet inclusion criteria anymore. In conclusion, we consider both methods as comparable and interchangeable in terms of achievement of MMR and of longitudinal evaluation of clinical courses. However, in LC/ABL1 negative samples, slightly enhanced TM/GUSB sensitivity may lead to inferior classification of clinical samples in the context of TFR.In chronic myeloid leukemia (CML), the duration of deep molecular response (MR) before treatment cessation (MR BCR and ABL1 is causal for development of chronic myeloid leukemia (CML).The occurrence of the reciprocal translocation between chromosomes 9 and 22 ) resulting in a translocation of the genes BCR-ABL1 mRNA fusion variants  resulting in the expression of abnormal BCR-ABL1 fusion tyrosine kinase. Molecular diagnostics of CML and patient monitoring is based on quantification of BCR-ABL1 transcript levels in peripheral blood (PB) or bone marrow (BM) aspirates of patients by various qRT-PCR technologies as the number of BCR-ABL1 transcripts serves as surrogate indicator for the amount of residual BCR-ABL1 positive tumor cells and/or their proliferative potential during therapy with tyrosine kinase inhibitors (TKI). Therapy regimen employing TKI directed at the abnormal BCR-ABL1 fusion tyrosine kinase can achieve durable cytogenetic and molecular remissions (MRs) and improve survival in the majority of patients which is approaching that of the general population .All clinical course data before January 2018 was LC/ABL1 based. Since then, TM/GUSB was used for GUSB combination on inclusion of patients in stopping trials we performed a “what if” analysis on a panel of 128 patients of the EURO-SKI stopping trial that have been previously monitored by employment of the LC/ABL1 combination. One sample of each patient representative of the screening period before inclusion in the stopping trial (i.e. MR4 mandatory for at least one year) was included in the analysis. Identical results were obtained for 114 patients irrespective whether LC/ABL1 or TM/GUSB was used for monitoring concerning MR4 in four and MR4.5/MR5 in 110 patients. Fourteen patients were re-classified to the next inferior log-level when using the TM/GUSB system. Altogether 12 patients were re-classified from MR4.5 to MR4. Of these 12, six patients showed relapse and the other six are still in TFR but are potential candidates for relapse and are under special attention. Upon hypothetic application of our “what if” scenario, the six relapsing patients were “saved” when inclusion into the stopping trial was restricted to MR5 and MR4.5 patients. Two patients of the relapse group were re-classified from MR4 to MMR and would not have led to cessation of treatment  (range: 0.00097 to 0.0097) whereas the TM/GUSB displayed a mean variation of 0.006 (+/- 0.0035) (range 0 to 0.0144). Wilcoxon signed rank test revealed significance (p = 0.0023) between both groups.We have added the variation ranges of actual TM/GUSB system is a robust and reliable qPCR method for monitoring CML patients. The TM technology for BCR-ABL1 quantitative measurements in our laboratory using the diagnostic combination TM/GUSB improved the sensitivity when compared to LC/ABL1 technology [GUSB and TM/ABL1, respectively, were re-classified to the next inferior log level when compared to LC/ABL1 results. This includes 16 of 19 patients who lost their MR5 status in TM/GUSB analysis, indicating that some (13 of 92) of the “BCR-ABL1-negative” samples tested may not be really negative if higher sensitive methods are applied. Albeit the slightly observed enhanced sensitivity of TM/GUSB that in some cases may lead to inferior classification of single data points, we consider both methods as absolutely comparable and interchangeable in terms of evaluating longitudinal clinical courses  and therefore lose their inclusion criterion.In fact, when comparing both PCR systems and generating a “what if” scenario for retrospectively selected cDNA samples of 128 EURO-SKI patients identical results were obtained only for 114 patients concerning MR4.5 to MR4 had no relapse during TFR in a follow up period of at least 24 month [GUSB qRT-PCR sensitivity. In the TM/GUSB PCR assay, there are differences in primer combinations and generated PCR amplicons. In determining the sensitivity of a PCR assay, primer selection and the length of the resulting PCR amplicons may play a crucial role. Shorter PCR fragments (length: 100–150 bp) are amplified in the TM system with higher efficiency. Furthermore TM and LC are different PCR systems with different PCR performance and kinetics. The TM technology uses only one labelled probe as a 5’ nuclease assay to generate a specific fluorescence signal instead of two probes, resulting in a simplification of the PCR kinetics which contributes to an increase in sensitivity. In addition, another type of Taq Polymerase used in TM technology could also influence PCR sensitivity and efficiency. Also the choice of the housekeeping gene may influence the diagnostic outcome. After careful testing and evaluating so far published data, we prefer GUSB as housekeeping gene for TM-based analysis. While Beillard et al. [ABL1 as control gene for RQ-PCR-based diagnosis and MRD detection in leukemic patients because of more stable, uniform expression and lack of pseudogenes, GUSB transcript levels were later confirmed as a suitable alternative [ABL1, BCR and GUSB for BCR-ABL1 quantification [GUSB) as the most suitable genes tested [GUSB) was found more homogenous than that of ABL1 or β2 microglobulin (B2M) [GUSB over ABL1 as housekeeping genes is the performance of BCR-ABL1 and GUSB quantification in one single well (duplex PCR) avoiding the bias introduced by setting-up two spatially distinct TM qPCR reactions.Six of the 14 patients re-classified from MR24 month . Furtherernative . Other as tested  because in (B2M) . Not to naturally observed for every assay system in particular when testing was performed for very low numbers of target molecules (compare 4.5 and MR5 where very few numbers (<10) of BCR-ABL1 cDNA molecules decide on sample positivity. This becomes evident in clinical courses of some representative patients shown in One could argue that the observed shift in log levels may purely reflect the variability of inter or intra-experimental variation or just pipetting inaccuracy,  compare . This maGUSB versus LC/ABL1 is merely due to an incorrect CF that may lead to erroneously high BCR-ABL1 IS quotients. Our CFs were established using Bland Altman method by the Australian laboratory of Susan Branford and/or the EUTOS consortium. However, the detection of BCR-ABL1 copies in 13 cases where LC/ABL1 did not succeed in detecting residual BCR-ABL1 transcripts (0.000% IS) is independent of the CF and therefore, our data point to higher sensitivity of TM/GUSB when compared to LC/ABL1. Therefore it seems not advantageous to us to change the CF by own calculation. The clinical relevance of the detection of minimal amounts of BCR-ABL1 copies using a more sensitive PCR system remains to be unclear and could be discussed controversially. Our preliminary data are a hint that increased sensitivity of the PCR system could play an important role in the scenario of stopping trials as being the basis for determination of MR4 and MR4.5 and therefore for the decision of treatment discontinuation. The duration and the log range of molecular remission is the factor with the highest predictive value for deciding on discontinuation of therapy. Therefore, the methods used to detect molecular remission play a crucial role. The deepening of the sensitivity of the diagnostic technologies depends on many different methodological factors. The quality of the RNA and the efficiency of the cDNA synthesis have an influence on the detected copy numbers of housekeeping gene and BCR-ABL1. A more efficient cDNA synthesis, together with a more sensitive PCR system, provides higher absolute copy numbers of BCR-ABL1 and housekeeping gene, which have an influence on the generation of the respective log level for the individual patient.One could further argue that the increased sensitivity of TM/GUSB diagnostic system resulted in detection of BCR-ABL1 copies in 13 cases where LC/ABL1 did not succeed in detecting residual BCR-ABL1 transcripts (0.000% IS). On the other hand, more sensitive systems generate the possibility to detect very high amounts of housekeeping gene copy numbers creating log level MR5.5 or even MR6, when a patient is in fact BCR-ABL1 negative by qRT-PCR. It should be emphasized that inclusion criteria should grant the lowest number of relapsing patients at long sight. Aiming at this, it is conceivable that omitting the MR4 log level as inclusion criterion may be advantageous for the outcome of future stopping trials.The increased sensitivity of the TM/GUSB combination may be advantages the BCR-ABL1 monitoring in some cases we consider both methods as comparable and interchangeable in terms of MMR achievement and evaluation of clinical courses. However, in LC/ABL1 negative samples, slightly enhanced TM/GUSB sensitivity may lead to positivity and inferior classification of clinical samples.In conclusion, although enhanced sensitivity of TM/5 and MR4.5BCR-ABL1 log levels may be clinically less important for the outcome of a stopping trial than the discrimination between MR4.5 and MR4, since the latter is nearby MMR. Our study is not meant to give statements about “correct” and “incorrect” methods, but is intended to serve optimization of molecular methods in terms of TFR-related settings.Our data suggests that in clinical terms the diagnostic discrimination of MRThe clinical impact of resulting changes needs to be further supported in large scale studies within stopping trials. We believe that the development of higher sensitive detection methods will positively impact on diagnostics and treatment of CML patients.S1 Fig(TIF)Click here for additional data file.


ObjectiveResidency program coordinators play an important role behind the scenes, in the function of residency and fellowship programs. In addition, coordinators have significantly heterogeneous job roles among institutions. The aim of this study was to evaluate the training, responsibilities, and contribution of residency program coordinators within the field of neurosurgery.MethodsA 24-question survey was submitted to 133 program coordinators, and 78 responses (59% response rate) were received.ResultsThe survey results showed that >80% of coordinators have been in their current position for ≥3 years. Coordinators identified at least 24 unique departmental responsibilities with an average of 85% of the time devoted to residency program management. Among coordinators, 82% reported no formal training, with 60% and 55% reporting inadequate training from their department and institution, respectively. Interestingly, 84% completely or partially agreed that their work is valued by residents, 91% by the program director(s), 78% by the department chair, 62% by other faculty, and 56% by other departmental staff. Lastly, 50% of coordinators reported that their department has not been receptive to receiving feedback on how to improve the roles of the position, with 80% reporting no career advancement track.ConclusionResidency program coordinators reported a wide range of experience and responsibilities within their respective departments. The majority reported limited training for their current position, and a significant number reported not feeling valued by members of their department, suggesting two areas for improvement. As coordinators continue to play a larger role in the management and accreditation of their departments, strategies to optimize their role may be important. Neurosurgery residency program coordinators play an important role in the organization and function of residency and fellowship programs. In addition to managing the daily operation of these programs, coordinators must manage Accreditation Council for Graduate Medical Education (ACGME) requirements for program accreditation in direct coordination with the program director(s), department chair, and other department staff -3. FirstCurrently, the ACGME Next Accreditation System, formed in 2015, governs the process of residency and fellowship program management. The demand placed on residency program coordinators has increased over the last decade as the ACGME requirements and other regulatory governance in neurosurgery programs have become more complex -5. TheseCurrently, there are several established Graduate Medical Education (GME) and ACGME requirements and guidelines for program coordinators, but except for the requirement that there must be a program coordinator with at least 50% of his or her time dedicated to the residency program, these are not consistent across specialties ,3,8. TheDespite the complex responsibilities of program coordinators, surveys among coordinators in other medical fields have shown that training for the position from institutions and departments is often not sufficient -2. The aAn anonymous 24-question survey was prepared for distribution to residency coordinators throughout the U.S. This survey was sent to 133 program coordinators working at ACGME-accredited neurosurgical residency programs.The survey included nine questions assessing the demographics of residency program coordinators, two questions about current roles and responsibilities, 12 questions surrounding the value of work and contribution, and one final question allowing coordinators to provide any information about their job they would add in addition to the survey  and Microsoft Excel . Continuous and discrete variables were analyzed using the T-test and Chi-squared test, respectively. The linear correlation of continuous variables was performed. All statistical analyses were completed using SPSS v22.0  with p<0.05 considered statistically significant.Residency program coordinator demographicsA total of 78 coordinators completed and returned the survey (59% response rate) Table . More thRoles and responsibilitiesMore than 85% of the responding residency program coordinators reported that their job duties included coordinating with the Electronic Residency Application Service (ERAS), Graduate Medical Education (GME), and National Resident Matching Program (NRMP) offices; participating in interview scheduling; completing paperwork for ACGME accreditation; providing residency orientation; completing rotation scheduling; and attending resident-program director meetings Table . Fewer tSelf-reported responsibilities listed under “other duties” included Continuing Medical Education (CME) coordination, scheduling visiting lecturers or professors, organization of medical student away and home rotations and shadowing, and other administrative tasks to include departmental budgeting, grants and awards, and departmental operations management.Value and contributionWe assessed the self-perceived valuation indicated by program coordinators Table . Fewer tThe self-reported valuation of coordinators was correlated among staff categories Table . That isThe aim of this survey was to assess the experience, training, responsibilities, and contribution of neurosurgery residency program coordinators. To our knowledge, no such study has been carried out previously. The importance of such a survey is in the increasing role that coordinators play a role in managing neurosurgical staff, monitoring regulatory affairs for accreditation, maintaining budgets, and performing human resources tasks, all of which allow departments to function and directly impact patient care.The response rate of 59% is consistent with surveys of program coordinators in other fields -3. OveraAlso consistent with other studies, residency program coordinators surveyed in our study reported inadequate training from both the institution and the department ,3. A barWorkplace training and responsiveness to feedback were common threads that impacted the valuation of program coordinators. The lack of formal training, standardized qualifications and expectations, or standardized job descriptions leaves coordinators with responsibilities that take their focus away from residency program management, a demanding task in and of itself. Without formal training, coordinators can quickly become burned out from many tasks that they do not feel qualified to manage. Respondents to our survey with inadequate department or institutional training correlated with a greater likelihood of feeling undervalued by the institution, department, department chair, and program director(s). Coordinators were more likely to feel undervalued by the institution or department if either was less responsive to feedback. A longer career in the position predicted a greater likelihood of feeling valued by the program director(s), very likely correlating with lower coordinator turnover and a better working relationship between coordinators and directors. Interestingly, no specific factors could be identified to suggest coordinators were undervalued by other faculty, fellows, residents, or other staff. These findings suggest that mechanisms to improve the onsite training of coordinators, specific to their job descriptions, and direct interaction with institutional administrators and other program leaders would be important to increase perceived valuation. Likely, as seen with longer lengths of employment and greater valuation from program directors, improved self-valuation results in greater job retention, although this was not specifically queried in this survey.Coordinators are also placed in a difficult and fast-paced educational environment, one that requires them to juggle working with residents and fellows, program directors, department chairs, and other faculty and staff. Our survey demonstrated that coordinators do not always feel valued by those with whom they work. Over 90% of coordinators completely or partially agreed to feeling valued by program directors with 84% reporting feeling valued by residents; however, the subjective perception of value decreased when coordinators were asked whether they agreed with feeling valued by the department chair, other faculty and staff, fellows, or the department and institution as a whole. In addition to this lack of perceived value, many departments in the field of neurosurgery do not offer a career advancement track for coordinators. This provides less incentive to receive certifications and additional training such as TAGME certification. Our data demonstrate that <15% of neurosurgery program coordinators are certified as such. If neurosurgery program coordinators are not properly valued and trained, the quality of residency program management may decrease at a time when residency program administration is becoming more complex.The high turnover rate among program coordinators demonstrated in other studies may be related to the lack of respect that coordinators reported they receive from those within the department ,3. The cThe limitations of this study include a subjective method of assessing roles, responsibilities, and perceived departmental value. Not all coordinators responded to this survey, which may result in a selection bias with viewpoints shared by a vocal number of individuals rather than the total. Further studies should investigate the training of residency program coordinators as well as possible solutions for the increasing managerial tasks among coordinators, which distract from the time involved in managing residency and fellowship programs.Neurosurgical residency program coordinators play an important role with regards to the function of the residency program and department, which impacts patients. Coordinators reported a wide range of experience and responsibilities within their department, with the majority reporting no formal or inadequate training for their current position. A significant number also reported not feeling valued by members of their department and nearly half agreed that departments and institutions are not receptive to their feedback about how to improve the role of coordinators. These findings directly impact the work product of the coordinators and serve as areas for improvement. As coordinators continue to play a large role in the management and accreditation of their departments, further exploration into strategies to optimize their training and role is warranted.


By contrast, body weight and FCR were both affected (p < 0.001) during the starter period. During the finisher phase, feed consumption was affected (p < 0.05) by dietary treatment. Feed intake of broilers fed on C, D3, D6, and D7 were statistically similar (p > 0.05)  and were higher (p < 0.05) than 1564.40 g/pen/day (D5). With the exception of drumsticks, neck, back thoracic vertebrae, and proventriculus weights, economical carcass segments were not affected (p > 0.05) by the dietary supplementation of amino acids. Duodenum and ileum weights and lengths decreased with amino acid supplementation (p < 0.05). IgT and IgG titers against Sheep Red Blood Cells (SRBC) for both primary and secondary responses were not affected by dietary treatments (p > 0.05). Dietary amino acids supplementation did not affect IgM titer after the secondary challenge (p > 0.05) and had a significant effect (p < 0.05) on serum antibody titers in broilers vaccinated against Newcastle disease (NCD) and Gumboro ‘s disease at the 27th and 30th days, respectively.L-carnitine as well as lysine and methionine are amino acids of important nutritional and nutraceutical interest and are used in nutritional strategies as diet supplements to improve feed quality characteristics in animals and broiler chicken in particular. This study investigated the effect of different levels of L-carnitine and extra levels of lysine-methionine on growth performance, carcass characteristics, and some immune system markers. Two hundred seventy male Ross 308 broilers were a fed control diet (C) and eight different diets supplemented with an excess of amino acids. In the experimental diets, identified as D1, D2, D3, D4, D5, D6, D7, and D8, extra L-carnitine, lysine, and methionine were added in excess with respect to the American National Research Council (NRC) recommendations: L-carnitine equal to NRC (D1); control diet supplemented with lysine at 30% in excess of NRC, methionine at 30% in excess of NRC, and L-carnitine equal to NRC (D2); control diet supplemented with lysine equal to NRC, methionine equal to NRC, and L-carnitine at 15% in excess of NRC (D3); control diet supplemented control diet supplemented with lysine at 15% in excess of NRC, methionine at 15% in excess of NRC, and L-carnitine at 15% in excess of NRC (D4); control diet supplemented lysine at 30% in excess of NRC, methionine at 30% in excess of NRC, and L-carnitine at 15% in excess of NRC (D5); control diet supplemented with lysine equal to NRC recommendations, methionine equal to NRC recommendations, and L-carnitine at 75% in excess of NRC (D6); control diet supplemented with lysine at 15% in excess of NRC, methionine at 15% in excess of NRC, and L-carnitine at 75% in excess of NRC (D7); and control diet supplemented with lysine at 30% in excess of NRC, methionine at 30% in excess of NRC, and L-carnitine at 75% in excess of NRC (D8). During the starter and growth phases, feed intake was not affected by dietary treatment ( Nowadays, the growing demand for poultry meat has resulted in pressure on breeders to increase the growth rate of birds, the feed efficiency, the size of breast muscles, and the reduction in abdominal fatness . TherefoIt has been also reported that the dietary supplementation of lysine and methionine can improve the immunity of broiler chickens against different diseases ,24,25,262+ and a number of vitamins , which are required as cofactors for the enzymes involved in the metabolic pathway of L-carnitine [−1 to the diet) led to significantly lower cholesterol levels vs. a low L-carnitine intake. To the knowledge of the authors, the effect of simultaneous feed supplementation with L-carnitine and excess lysine-methionine on growth performance, carcass characteristics. and immunity markers of broiler chicken has not been studied before.L-carnitine supplementation is used to improve broiler productivity , and itsarnitine ,34,35,36arnitine , while oarnitine . Nonethearnitine  and Celiarnitine  showed tarnitine  evaluatearnitine  reportedThere is a need to standardize the dose of lysine-methionine and L-carnitine supplementation in the diet of broiler chickens not only to enhance their growth performance and carcass characteristics but also to improve their immune response. Hence, the main objective of this study has been to evaluate the effect of dietary supplementation of different levels of L-carnitine with or without an excess of lysine-methionine compared to dietary nutrient requirements on broiler chickens’ growth performance, humoral immunity markers, and carcass characteristics during a 6-week rearing trial.All procedures related to animals’ care and sampling were conducted under the approval of the Institution’s Ethic Committee at the Department of Animal Science, Rasht Branch, Islamic Azad University, Rasht (Iran) (protocol N° 105/19) before the beginning of the experimental trial.A control diet (C) for broiler chicken based on corn and soybean-meal was prepared according to the dietary nutrient requirements of broilers . The ingAs stated above, the L-carnitine, lysine, and methionine levels in starter, grower, and finisher feeds for the control diet were determined according to the NRC  recommenTwo hundred seventy 1-day-old, male Ross 308 broiler chicks obtained from a local commercial hatchery were used in this experiment. Chicks were randomly distributed into 27 pens . Each group was allocated to one of the 9 dietary treatments indicated above. Birds were given starter feed from 1 to 21 days, a grower feed from 22 to 35 days, and a finisher feed from 36 to 42 days of age. Feed and water were provided ad libitum throughout the experimental assay. For the growth performance traits, the experimental unit was the pen. For the carcass and immunity traits, the experimental unit was the chicken.st, 21st, and the 35th days of age to determine the live body weight and the weight gain. The feed consumption and feed conversion ratio (FCR) were also calculated for each growing phase as follows: from the 1st to the 21st day, from the 22nd day to the 35th day, and from the 36th to the 42nd day of the 42 days experimental study as described by Bouyeh and Gevorgyan [Tens birds per pen were weighed together on the 1evorgyan .n = 3) were randomly selected, weighed without prior fasting, and scarified between 9:00 am and 10:00 am by cervical dislocation to evaluate the characteristics of the carcass. After skin removal and total evisceration, the feet were separated from the carcass in the tibio–tarsal joint. Economic carcass and gastrointestinal segments were removed, weighed, and the ratios of each segment to body weight were calculated.As shown by Panda et al. ,44,45, an = 6) were subcutaneously injected in the breast with 0.5 mL of SRBC suspension on the 22nd and the 36th days of the experimental trial.Non-pathogenic antigens of Sheep Red Blood Cells (SRBC) were used to monitor the humoral immune response of broilers. The SRBC were purchased from a local Iranian supplier. A suspension was prepared by mixing 1 mL of phosphate-buffered saline (PBS) with 10 mL of SRBC. Six birds per same treatment  , antibody titers against SRBC were measured by a hemagglutination inhibition (HI) test according to Cunningham . All antst and 16th days of age, against Newcastle disease (NCD) on the 8th and 20th days of age, and against Gumboro’s disease on the 14th and 23rd days of age. The humoral immune responses of chickens to the IB virus at the 23rd day of age, to the NCD virus at 27th day of age, and to the Gumboro virus at the 30th day of age were measured using the HI and ELISA methods as described by references [g rpm for 15 min), and antibody titers against IB, NCD, and Gumboro virus were measured using commercially available ELISA kits  according to the manufacturer’s instructions. The absorbance of controls and samples were read at a wavelength of 405 nm using an ELISA reader .Birds were also vaccinated against infectious bronchitis (IB) on the 1ferences ,48. Blooijk = the jth observation on the ith treatment, µ = overall mean, αj = the main effect of the L-carnitine level, βK = the main effect of the methionine-lysine level, αβjk = The effect of the interaction of L-carnitine and of methionine-lysine treatments, and ɛijk = The random errorAll data were subjected to an ANOVA statistical analysis with the General Linear Model (GLM) procedure of SAS . The GLMp > 0.05). By contrast, body weight and FCR were both affected (p < 0.001) during the starter period. In fact, D1, D2, D3, D6, D7, and D8 were associated with the highest live body weight (p < 0.001) with mean values of 706.31, 745.50, 671.10, 733.67, 741.00, and 723.27 g/pen/21day, and consequently, the feed conversion ratio was the lowest (p < 0.001) during this period compared to the Control Diet (C).p < 0.001). D1 and D2 were associated with the lowest feed conversion ratio (p < 0.001) with mean values of 2.33 and 2.48, respectively. During the finisher phase, feed consumption was affected (p < 0.05) by dietary treatment. Feed intake of broilers fed on C, D3, D6, and D7 were statistically similar (p > 0.05)  and were higher (p < 0.05) than 1564.40 g/pen/day (D5).However, during the grower period, the live body weight of the broiler fed on D1 and D2 was not different from that of C (1241.29 g/pen/period and 1165.50 g/pen/period vs. 1207.10 g/pen/period) and was higher than those of D3, D4, D5, D6, D7, and D8 (p > 0.05) with mean values of 1976.53 g/pen/period and 1949.27 g/pen/period, respectively. The FCR of this period was not affected (p > 0.05) by dietary treatment.However, live body weights were similar between dietary treatments  are shown in p > 0.05). The neck weights of the bird given D1 and D8 were the highest (p > 0.05) with mean values of 64.50 g and 64.63 g, respectively, compared to 79.57 for the control diet. D2 was associated with the highest back thoracic vertebrae weight (p > 0.05) at 103.99 g versus 45.11 g for birds given the diet D8. However, all other body segments  weights were not affected by dietary treatment (p > 0.05). With the exception of proventriculus weight, gut organ weights were not affected (p < 0.05) by dietary treatment. Our data showed that the dietary supplementation of lysine and methionine at 30% with a level of L-carnitine equal to NRC and of 15% of lysine, methionine, and carnitine increased (p < 0.05) proventriculus weight from 10.77 g to 11.26 and 11.43 g, respectively.Our results indicate that, with the exception of thigh weights, economical carcass segments were not affected by dietary treatment  in broilers are shown in p < 0.05) duodenum weight and length. Birds given a supplemented diet with 30% of lysine and methionine in excess of NRC and 75% of L-carnitine in excess of NRC had the lowest weight, with a mean value of 12.99 g. The lowest duodenum length was recorded when birds were given 15% of lysine and methionine in excess of NRC plus 75% of L-carnitine in excess of NRC. A combination of L-carnitine (75%) and lysine-methionine (30%) increased the duodenum width significantly (p < 0.05) from 7.50 mm to 9.38 mm. Concerning the duodenum diameter, the dietary addition of lysine-methionine at a level equal to NRC plus 15% of L-carnitine in excess of NRC (D3), of lysine-methionine and L-carnitine at a rate of 15% in excess of NRC (D4), and of lysine-methionine and L-carnitine at a rate of 30% in excess of NRC plus 15% of L-carnitine in excess of NRC (D5) increased the diameter from 0.94 mm (C) to, respectively, 1.61mm, 1.67 mm, and 1.68 mm.The dietary supplementation of amino acid decreased (p > 0.05) the jejunum weight and length. The dietary addition of lysine-methionine at a level equal to NRC plus 15% of L-carnitine in excess of NRC (D3) and of lysine-methionine and L-carnitine at a rate of 15% in excess of NRC (D4) increased the jejunum width (p < 0.05) from 9.26mm (C) to 9.50 mm (D3) and 9.80 mm (D4). The dietary supplementation of amino acids significantly decreased (p < 0.05) the ileum weight from 9.10 g (C) to 2.67 g (D4) and 2.97 g (D7) and the length from 18.16mm to 9.26 mm (D8) and 8.00 mm (D7). The ileum width of the broiler group fed with lysine-methionine at a level of 15% plus L-carnitine at 75% in excess of NRC was the highest (p < 0.05) compared to the control diet 7.33 mm versus 7.97 mm (D7). Dietary treatment did not affect (p > 0.05) ileum diameter.Dietary treatments did not affect (p > 0.05). The colon weight of broiler bird fed with lysine-methionine at a level equal to NRC plus 15% of L-carnitine in excess of NRC (D4) was the highest (p < 0.05), with a mean value of 2.36 g. Rectum weights were similar between all the treatments groups and ranged from 1.78 g (D6) to 2.32 g (D7) (p > 0.05).Caecum weights were not different between treatments and ranged from 12.62 g (D5) to 17.13 g (C) (p > 0.05). Birds receiving diets supplemented with excesses of amino acids  had significantly lower titers of IgM than that of those receiving C for primary response (p < 0.05), with mean values of 2.33 log10 versus 2.00 log10 (D1); 1.66 log10 (D2); 1.33 log10 (D3); 1.33 log10 (D4); 1.00 log10 (D5); 1.33 log10 (D6); 1.33 log10 (D7); and 2.00 log10 (D8). Dietary treatment did not affect (p > 0.05) IgM titer after a secondary challenge.The dietary effect of amino acids supplementation on primary and secondary antibody responses are shown in the p > 0.05) by dietary treatment on day 23. However, a significant increase (p < 0.05) in serum antibody titers in broilers vaccinated against NCD and Gumboro on the 27th and the 30th days was observed from, respectively, 3.66 log10 (C) to 6.00 log10 (D3) and from 3.38 log10 (C) to 3.59 log10 (D6). Chickens fed with 30% of lysine-methionine in excess of the NRC and of L-carnitine equal to the NRC supplemented diet had the heaviest thymus (p < 0.001) with a mean value of 24.60 g versus 15.59 for the control diet. However, chickens fed on L-carnitine (15%) and lysine-methionine (15%) in excess of the NRC had the lightest thymus with a mean value of 7.17 g. Bursa of fabricius and spleen weights were not affected (p > 0.05) by dietary L-carnitine and lysine-methionine supplementation.The influence of different amino acids dietary supplementations on serum antibody titer in chickens vaccinated against IB, NCD, and Gumboro virus are shown in It has been observed that L-carnitine supplementation can enhance broiler productivity . HoweverThe results relative to the growth performance show that a combination of lysine and methionine at 15% and 30% in excess of the NRC recommendations was without impact on the feed intake, live body weight gain, and FCR of broiler chicken during the whole experiment period.Live body weights at the end of the experimental trail varied from 2828.60 g (D2) to 3602.70 g (D4). These values are consistent with those reported by Bouyeh and Gevorgyan , who shoOn the other hand, Hickling et al.  showed tWith regard to the L-carnitine dietary supplementation, our results show that a dietary inclusion of L-carnitine at 75% or 15% in excess of NRC recommendations increased the live body weight, feed intake, and FCR of 308 Ross broilers. In this respect, our data are in line with those obtained by Celik et al. . These aAs far as L-carnitine was concerned, the results reported here are consistent with those reported by Rodehutscord et al.  and by FOur data show that the dietary combination of L-carnitine, lysine, and methionine had a significant effect on growth performance. In fact, L-carnitine is an amine compound biosynthesized primarily in the liver from the amino acids lysine and methionine. It is involved in energy metabolism, where it is required for the transport of long-chain fatty acids into the mitochondrial matrix for β-oxidation by the fatty acid oxidation complex . One theAdding 75% of L-carnitine plus 15% or 30% of lysine-methionine or 15% of L-carnitine plus 15% of lysine-methionine had a significant effect on feed intake and live body weight at the end of the experimental trial. Furthermore, adding 15% of L-carnitine plus 30% of lysine-methionine had no benefit and actually reduced feed intake and body weight and increased FCR significantly compared to the control.To our knowledge, no information related to the effect of supplementing L-carnitine in combination with lysine-methionine on broiler growth performance is reported in the literature until now.With the exception of drumsticks, neck, back thoracic vertebrae, and proventriculus weights, all other economical carcass segments weights were not affected by the dietary supplementation of L-carnitine and lysine-methionine. With respect to lysine-methionine supplementation, Mukhtar et al.  studied th and 42nd days of age.In the present study, the dietary supplementation of lysine-methionine and L-carnitine had a significant effect on all intestine segments with the exception of jejunum weight and length, ileum diameter, and caecum and rectum weight. As far as we know, the effect of simultaneous dietary supplementation with lysine-methionine and L-carnitine on intestine segments is not documented. Some studies underline the relationship to villi surface area to better feed utilization, higher nutrient absorption, body weight gain, and growth performance ,60. HoweIgM primary response against the SRBC of birds fed with supplemented diets with L-carnitine and lysine-methionine was significantly lower than that of birds receiving the unsupplemented diet. No significant differences have been observed among dietary treatments for IgT and IgG titers against SRBC during both primary and secondary antibody responses. Latshaw  reportedth week but that birds fed on a diet with 1000 mg of L-carnitine had a higher primary antibody response against SRBC than broilers in other groups at the 12th week. Moghaddam and Emadi [Reports on the effect of methionine supplementation on broiler chickens’ humoral immune response are lacking. However, as far as L-carnitine was concerned, Deng et al.  found thnd Emadi  reportedThe findings of this study suggest that the dietary supplementation of L-carnitine solely or in combination with excesses of lysine or methionine (with respect to NRC recommendations) did not affect body weight gain, feed conversion, and economical carcass segments of broiler chickens. By contrast, the diet with around 30% of lysine-methionine content increased the back thoracic vertebrae and the proventriculus weights. A combination of lysine-methionine  with L-carnitine (15% and 75%) improved the immune response of broiler chickens against Newcastle and Gumboro diseases by stimulating the antibody production.


Boys and young men have unique health-related needs that may be poorly met by existing programs and initiatives. The mismatch between the needs of boys and young men and current service offerings–driven largely by social determinants of health such as masculinity–may stymie health status. This is evidenced through high rates of self-stigma, accidental death or suicide, and low rates of help seeking and health literacy among populations of boys and young men. With growing interest in improving wellbeing and educational outcomes for all young people (including boys and young men), this systematic review aimed to evaluate community and school-based programs with specific focus on program features and outcomes directly relevant to young males aged 12–25 years. Five data-bases were searched; Medline, EMBASE, PsycInfo, ERIC, and ERAD. Articles were included if they evaluated an intervention or program with a general or at-risk sample of young men, and measured a psychological, psychosocial, masculinity, or educational outcome. The majority of the 40 included studies had high quality reporting (62.5%). Synthesised data included theoretical frameworks, intervention characteristics, outcomes, and key results. Of the included studies, 14 were male-focussed programs, with masculinity approaches directed towards program aims and content information. The emergent trend indicated that male-targeted interventions may be more beneficial for young men than gender-neutral programs, however, none of these studies incorporated masculine-specific theory as an overarching framework. Furthermore, only three studies measured masculine-specific variables. Studies were limited by a lack of replication and program refinement approaches. It is concluded that there is significant scope for further development of community and school-based health promotion programs that target young men through incorporation of frameworks that consider the impact of gendered social and environmental determinants of health. Evaluation of these programs will provide researchers and practitioners with the capacity for translating beneficial outcomes into best-practice policy. Young men exhibit distinct health and service engagement profiles from that of their female and adult male counterparts . It is wSocial determinants of health, in particular masculinity , are impIn the health promotion field, previous systematic reviews have investigated mental health and intimate partner violence prevention programs in mixed-gender adolescent and young-adult samples, reporting improved outcomes from group-based and experiential programs that focus on health promotion across both community and school settings , 27. RevThere are currently no published systematic reviews that have specifically investigated engagement with health and positive identity promotion programs for young males that are community and/or school-based. Given schools are increasingly viewed as venues for such initiatives , especiaA systematic search of five psychological, medical, and education databases  was conducted for all articles up to September 2018, with the advice of a research librarian. The keywords used for searching can be found in Two authors (KG and SMR) independently reviewed eligibility of the sourced records based on the title and abstract. Studies included were based on the following inclusion criteria: (a) male sample or gender data analysed and reported separately for male and female samples; (b) mean age between 12–25 years at the beginning of intervention; (c) implementation of an intervention or health promotion program ; (d) psychological, psychosocial, masculinity, help-seeking or educational outcomes measured; (e) general or at-risk samples . Studies excluded were based on the following exclusion criteria: (a) all female samples; (b) studies focussing on youth offenders, clinical or out-patient samples; (c) case studies; (d) biological, medical or supplementary  interventions; (e) outcome variables relating to reproductive health behaviours , partner violence, substance use, physical health , smoking and program feedback only. Authors collaboratively discussed and agreed upon inclusion of any studies where application of the inclusion and exclusion criteria was unclear. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines  designed a standardised data extraction template. KG sourced relevant information including study design, intervention type, intervention setting, theoretical framework, masculinity focus, outcome measures, sample characteristics, assessment schedule, and key results; SMR reviewed data for consistency. Masculinity focus was evaluated using the World Health Organisation’s classifications of programs . An inteTwo established quality appraisal tools were used, the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Quasi-Experimental Studies, and the JBI Critical Appraisal Checklist for Randomized Controlled Trials (RCTs). The appThe literature search returned 5197 articles. After removal of duplicates and screening of titles and abstracts, 139 full texts were assessed for eligibility. A total of 40 studies met the inclusion criteria and were assessed in the final review . Data were collected pre and post intervention in 35 of 40 articles (87.5%). Follow-up data were collected in 16 of 40 articles (40%), with the length of follow-up spanning from two months to two years after the intervention or program. The mean length of follow-up was 8.6 months.Intervention types and settings are listed in The focus for all four gender-transformative programs was the development of healthy masculine identity , 44, 47.Studies reporting results for The Council, YMI, and TRJ reported relevant theoretical frameworks for their respective programs. The Council was based upon resiliency principles and relational-cultural theory, focussing on growth and development that occurs through connection, mutual empathy, and empowerment . Peer-grn = 3) was equal to the number that reported no changes.Each of the four gender-transformative interventions reported some positive changes in participants post-program. The Council was the only gender-transformative program to report quantitative outcomes, with significant positive intervention effects observed for school self-efficacy and future self-efficacy. Notably, no changes were found for masculine ideology, relational aggression or identity distress . The YMIThere were 10 articles evaluating gender-sensitive programs, of which seven were unique interventions. Four articles assessed physical activity interventions, with three evaluating the ‘Active Teen Leaders Avoiding Screen Time’ (ATLAS) program , 64, 75,n = 6) of the gender-sensitive interventions were implemented in high-schools, or with groups of students [Two papers evaluated one eHealth intervention, ‘Reach Out Central’ (ROC) , 71, an students , 73, 75.Self-determination theory (SDT) was the foundation of both physical activity interventions , which posits that satisfaction with three basic psychological needs of autonomy, relatedness, and competence is associated with self-driven motivation . AchieveAll seven male-specific interventions reported at least one beneficial outcome in young men. Post-program, participants of the physical activity interventions, HEYMAN and ATLAS, reported increased quality of life enjoyment and satisfaction, and psychological wellbeing, respectively , 64. Forn = 4; [n = 4; [n = 4; [n = 5, 4 unique programs; [n = 18, 69%), seven programs were delivered in all boys schools (39%), and 11 in coeducational schools (61%). Programs were generally delivered by outsourced trainers or using external platforms . The shortest program was 90 minutes long and the longest program ran for one year, with an average duration of 14 weeks. Typically, programs were implemented for 1–2 hours per week . Shorter intensities included a 2-hour psychoeducation program [For the 26 articles assessing programs without a specific male or masculinity focus, the most common type of intervention was mentoring or community service n = 4; , 53, 63), 63n = 4 [n = 4; , 60, 70) [n = 4; , 66, 68)rograms; , 59, 76)rograms; , 46, 72,rograms; , 49, 57,rograms; , 65, andrograms; . For sam program , 42, and n = 14; %. Shorte schools %, and 11 schools %, and 11 n = 14; %. Shorte program , 76), wiFrameworks typically reflected the intervention type, for instance, the emotional ability model was the basis for both emotional intelligence programs. The experiential learning framework was used for the outdoor adventure programs, positive psychology models provided the framework for two psychoeducation programs and one mindfulness program. CBT principles were integrated into one psychoeducational and one eHealth intervention. Singularly implemented frameworks included social-learning theory, hopelessness theory, attachment theory, cooperative learning theory and emotional regulation principles.There were nine gender-neutral programs that investigated outcomes in male-only samples, of which eight (89%) reported positive effects in young men for at least one outcome. Of these, two outdoor adventure programs reported significant increases in self-efficacy and cognitive autonomy , and emoThe remaining 17 articles evaluated gender-neutral programs in mixed-gender samples. Of these articles, seven 41%) reported positive changes in mostly males, six (35%) reported intervention effects in mostly females, three (18%) found positive changes in both genders, and one (6%) reported no intervention effects in either gender. The seven programs with benefits in boys included two psychoeducational programs that improved mental health , and sel% reporteThe appraisal score (in proportions) for the 40 studies ranged from moderate (0.5) to excellent (1.0). The average appraisal score was 0.85, with the majority of studies reporting high quality , where high quality is regarded as ≥ 0.8. Of these studies, nine met all appraisal criteria. There were 15 studies (32.5%) with moderate quality , and none reporting poor quality (<0.5). For the eight RCTs, all articles used true randomisation techniques, compared similar participant groups, measured variables consistently across groups, accounted for incomplete follow-up, and used appropriate statistical analysis. None of the eight RCTs blinded participants, or research staff delivering the interventions. For the remaining 32 studies, control group use , and complete follow-up  were the lowest scoring criteria. Complete quality appraisal information can be found in The aim of this review was to identify and appraise the potential effectiveness of school and community-based health and wellbeing programs in young men. The articles identified in this review evaluated a range of intervention types, durations, and intensities. On average, interventions were implemented for 18 weeks, typically through 1–2 hour weekly sessions. Overall, findings support the effectiveness of health promotion programming for boys and young men, especially in gender-focussed interventions and school-based environments, which comprised the most frequently used intervention setting. The percentage of programs reporting positive effects in young men is encouraging , suggesting that participation in these programs, despite the varying aims and activities, is likely to be valuable. Nonetheless, a need remains to determine which approaches work best. While heterogeneity in intervention types, foci, and outcomes of studies included in the present review prohibited meta-analysis, this should be considered as a priority as the field develops, and randomised trials and replication studies are undertaken. It was also clear from results that there is growing interest in the health promotion field for boys and young men, as 55% of included studies were published from 2014 onwards. Despite this growing interest, further investigation is needed for the development of a robust evidence base, critical for well-informed recommendations regarding program development and implementation. This review synthesised findings from a high quality pool of literature , with a majority of articles reporting controlled methods with multiple assessment points.An important aspect of this review involved identifying those approaches that incorporated a specific focus on masculinity, a key social determinant of the health of boys and men . PreviouIn this review, 10 of the 14 articles that incorporated a masculinity focus evaluated gender-sensitive programs, and four evaluated gender-transformative programs. Encouragingly, all four of the gender-transformative programs reported beneficial outcomes in young men across a range of outcomes, including self-efficacy, anger, and perceptions of manhood. The overarching aim of these four programs however was to help young males develop their own healthy masculine identity, and the relative success of these programs in achieving this aim is less clear. Indeed, there is a need to identify and define the determinants of what actually constitutes (and does not constitute) a healthy masculine identity. While this work is beyond the scope of the present study, it is likely essential to furthering research rigour and scholarship in the domains of young men’s health . ParticiSimilarly, all ten articles evaluating gender-sensitive interventions also reported positive outcomes in young males. The aims of these interventions were focussed on improving self-esteem, school engagement, physical activity and mental health awareness in young men. The effectiveness of these programs are evidenced by improvements in the outcomes related to intervention aims. For instance, the OBBC had a focus on school engagement and reported increased academic self-esteem in participants. Moreover, the body-image and physical activity interventions found improvements in self-esteem, negative affect, quality of life enjoyment, and psychological wellbeing, all of which are constructs that have been repeatedly linked with positive body-image and physical activity , 84. LasA number of gender-neutral programs were also effective for health promotion in boys and young men. Notable improvements were found for measures of self-efficacy, competence, negative affect, and depressive symptoms. These benefits were commonly identified following programs with a focus on experiential learning and shared-activity, for instance outdoor adventure, sporting, and exercise interventions. This aligns with men’s preferences for group interaction and informal spaces as facilitators to engaging with mental health services . DespiteThe reported lack of improvement in young men’s mental health stigma may be associated with low program engagement. Stigma has been repeatedly recognised as a key barrier to access and engagement with mental health services for boys and young men , 88–91. Theoretical frameworks supporting the interventions were diverse, with 22 different theories implemented across areas of learning, cognition, motivation, socialisation, and culture. However, common themes of socialisation and connectedness emerged when assessing program frameworks associated with positive outcomes in young men, especially in gender-transformative and gender-sensitive interventions. The health benefit of social support in young men is associated with enhanced wellbeing . Socialin = 7; 17.5%), is problematic for program evaluation and understanding theorised mechanisms of change, and hinders the development and refinement of future health promotion programs for boys and young men. Moreover, none of the male-focussed interventions incorporated masculine-based frameworks, instead citing general psychological frameworks including cognitive behaviour therapy or self-determination theory [Unfortunately, the frequency of articles that did not mention any theoretical frameworks  framework , and theThis review found a high percentage of studies evaluating programs in secondary-school settings . Schools are unique environments for program implementation given students experience connection in an established community with corresponding social values. Moreover, secondary students are at a developmental stage where social and self-identity is in a state of rapid development . Howevern = 12), with only a handful of trained school staff delivering the program (n = 4). Building the capacity and experience of internal school staff to facilitate school-based programs is likely to be an important aspect of program sustainability. Future research should look to identify any barriers and facilitators of program delivery by internal staff.Schools are also ideal settings for programming around health-related attitudes, as they embrace an interconnected community system including parents, staff, and alumni . ProgramFrom this review, it is apparent that there are health promotion programs being delivered to a large number of secondary students without extensive research evaluation. For example, the RWP intervention cited delivery to over 2 million students worldwide , though Due to the broad approach taken in this review, the resulting heterogeneity of study characteristics prevented a meta-analysis or assessing publication bias. The possibility of publication bias is considered as most of the 40 included studies reported at least one significant effect, suggesting that studies failing to report an effect may be less likely to be published. Heterogeneity additionally hindered the ability to draw statistical comparisons for specific outcomes, settings, and designs. This review was also limited by the inclusion of studies reported in English only. Review of non-English articles is critical to obtain a comprehensive understanding of the literature, unfortunately we were unable to do so in the scope of this review.Despite the potential effectiveness of masculine-focussed programming, evaluation of young men’s conformity to traditional masculine norms was limited in this review by the small number of studies incorporating a direct measure of masculinity. It is noteworthy that so few studies seeking to engage boys and young men in attitudes related to masculinity actually sought to measure the construct . There aLimitations of the included articles and therefore of this review include a lack of long-term intervention, follow-up, and program refinement. The majority of evaluations were conducted for relatively short-term programs that would run once a week for 4–12 weeks. Moreover, it is noteworthy that none of the gender-transformative interventions reported follow-up data. Future studies should collect this data to evaluate sustained or long-term intervention effects. There were also no instances of study replication, though one program was suspected to have been developed from an earlier iteration of the same program , 73. TheFrom this review, we can determine that there is still a large amount of research and program development that needs to occur before researchers have the capacity for translating beneficial outcomes into best-practice policy. Specifically, there is scope for the development of programs directed to young men founded in masculinity frameworks and further quantitative assessment of masculinity variables, such as male-norm adherence and masculine identity-distress, in male-targeted interventions. Alongside this need, documentation of program development should also increase in order to assist future development of similar health promotion programs in young men.This review supports the use of community and school-based programs in fostering health, wellbeing, and identity development in boys and young men. Such initiatives are needed in order to provide boys and young men with ‘teaching moments’ to develop necessary skills and attributes they may otherwise not develop. Incorporation of male-targeted approaches through gender-sensitive and gender-transformative programs may also benefit young men’s mental health and wellbeing. There remains a need for research and development of health promotion programs that specifically target young men through incorporation of frameworks that consider, but not necessarily reinforce, gendered social and environmental determinants of health . It is imperative that researchers, program developers, and educators jointly collaborate to strengthen gender-responsive programs that foster healthy lifestyles and wellbeing in young men. Such approaches are likely to positively impact the ways in which boys and young men relate both to others and themselves, and reduce the unnecessary mortality and morbidity associated with boys and young men’s maladaptive behaviours and attitudes.S1 Material(DOC)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 Tablea. Quasi-experimental quality appraisal–Joanna Briggs Assessment; b. RCT quality appraisal–Joanna Briggs Assessment.(DOCX)Click here for additional data file.