Purpose: The objective of this study is to investigate the perceptions of healthcare providers about the use of social media for healthy diet management in Saudi Arabia.Participants and Methods: A cross-sectional study was designed to investigate the use of social media healthy diet management. The sample constituted 308 healthcare professionals from Saudi Arabia. The social media application, WhatsApp is employed to distribute the questionnaire, which has achieved a response rate of 50.61%. Out of the total participants, 55% of the participants were under 30 years of age, 71% were females, and 55% of the participants had a bachelor's degree.Results: Among the total respondents, 66% used social networking applications more than four hours a day, and 78% utilized social media to get information about a healthy diet. The respondents employed the following platforms for this purpose: Instagram (27%), YouTube (19%), Snapchat (19%), WhatsApp (18%), Twitter (8%), and Facebook (5%). The respondents considered that social media is very helpful to educate (44%), communicate with specialists (33%), and get applications for a healthy diet (38%). They held an opinion that social media is very helpful in improving knowledge about a healthy diet (47%), creating diet awareness (42%), and achieving healthy diet outcomes (37%) and lifestyle (37%).Conclusion: According to the perception of health providers, social media can be used to promote healthy diet management in Saudi Arabia. Also, the growing use of social media in Saudi Arabia represents the potential to create programs that encourage and promote healthy eating habits in the Kingdom of Saudi Arabia. Instagram, YouTube, Snapchat, and WhatsApp platforms can be used for this purpose. In general, social media platforms display articles, advertisements, videos, blogs, and various types of information related to nutrition, food, beverages, recipes, diets, physical exercise, and other issues related to the search for a healthy lifestyle , 2.In addition, these tools are increasingly used to provide information on nutrition, food, and health promotion interventions –5. TheseObviously, a diet with healthy habits combined with physical exercise, that is, a behavioral diet, leads to the prevention of diseases and promotes a good state of physical and mental health and well-being. On the contrary, an unbalanced diet without healthy dietary habits and without fiscal exercise can lead to various health issues, such as obesity, being overweight, cardiovascular diseases, diabetes, cancer, metabolic disorders, and other health problems .It is convenient to indicate that the use of social media to disseminate knowledge and exchange information on nutritional topics increases every day, but its use is still incipient , 6. As iOn the other hand, it is convenient to point out that according to several studies, part of the information published on social media is not accurate and does not allow achieving a healthy diet. , 11–13. In relation to Saudi Arabia, a national survey with 10,735 participants revealed that a high percentage of the population did not have a healthy diet, indicating that it is necessary to develop programs to promote healthy eating habits and avoid diseases caused by poor diet . AdditioParallel with this situation, the use of social networks in Saudi Arabia has increased progressively in recent years, impacting the different activities carried out in this country . As of JAccordingly, the research studies in Saudi Arabia focused on the social media applications in health management from different perspectives. For instance, Aldossari and Al-Mahish study  focused Therefore, the objective of this study is formulated to investigate the perceptions of healthcare providers about the use of social media to manage a healthy diet in Saudi Arabia.In this research, a cross-sectional survey is designed to investigate the use of social media to manage a healthy diet. The sample population constituted 308 healthcare professionals from the Kingdom of Saudi Arabia. A response rate of 50.61% was achieved. The informed consent from the participants was gathered before the survey. Ethical approval was provided by the Abdulrahman Bin Faisal University, Saudi Arabia.All healthcare providers living in Saudi Arabia were included in this study.The questionnaire survey was distributed to the participants using WhatsApp and other social media platforms, and the data was collected in January 2019.The questionnaire used in the survey was designed by the research team and contained nine items that pointed to the collection of data relating to the main objective of the study . The queThe first four items were aimed at obtaining demographic information of the participants: age, gender, level of education, and professional specialty. Item 5 asked about the number of hours that participants used social media. Item 6 inquired whether participants obtained information about a healthy diet through social media (Yes-No). Item 7 examined the type of social media used by the participants to obtain information about a healthy diet . Item 8 contained several questions with the intention of evaluating the utility of social media as a tool to achieve a healthy diet ; these questions were evaluated using the scale: very helpful, some helpful, not helpful, not applicable. Finally, item 9 asked the question, Do you think that social media helps you to reach a healthy behavioral diet and encourage people for a healthy diet? (Yes- No).Standard computation methods were used in calculating basic descriptive statistics. The data were expressed in percentages, and the mean (M), the standard deviation (SD), and the confidence interval (CI) 95% were estimated and are presented in the tables and figures of the Results section.The demographical information of the healthcare providers surveyed in this study is shown in In relation to the daily use of social media, Also, in In addition, according to On the other hand, in Lastly, The results of this study related to the perception of health providers to manage a healthy diet in Saudi Arabia indicated that most participants considered that social media was useful for this purpose.In this sense, in The findings in this study suggested that young people aged <30 years prefer social media and use it extensively for healthy diet management in similar to the study conducted by Klassen et al. . In addiFrom On the other hand, the most used social media platform to obtain information about a healthy diet are in descending order: Instagram, YouTube, Snapchat, WhatsApp, Twitter, and Facebook. In this regard, in previous studies, it has been found that Instagram was one of the most-used platforms for disseminating information related to food and diets , 33.Low sample size was identified as the main limitations of this study and the fact that some of the participants did not answer all the questionnaire questions, which resulted in a low response rate. Therefore, future studies should aim to overcome these limitations and develop programs to encourage the population to improve their eating habits using social media for this purpose.It is pertinent to comment that our study is the first research conducted in Saudi Arabia with the intention of knowing the opinion of health providers about the use of social media to achieve healthy diet management.The perceptions of the majority of the surveyed healthcare providers indicated that social media can be useful for healthy diet management among the population of Saudi Arabia, enabling them to maintain a good state of health and well-being. In addition, the increasing use of social networks in this region suggested that there is a huge potential for integrating educational and social programs with social media applications for creating awareness to encourage and promote healthy eating habits in the Kingdom of Saudi Arabia. Considering the most frequently used platforms, Instagram, YouTube, Snapchat, and WhatsApp platforms may be the best options for creating awareness about healthy diet management. The findings in this study can have both practical and theoretical implications. First, the findings contributed to the lack of research in the application of social media for healthy diet management in Saudi Arabia through the lens of healthcare practitioners. Second, the findings can be used by the healthcare authorities in selecting the social media types and formulating the promotional and awareness plans for maintaining healthy lifestyles and adopting healthy diets among the Saudi Arabian population. However, there are few limitations that need to be considered while interpreting the results of the present study. First, a low sample population makes it hard to generalize the results. Therefore, results should be generalized with care. Second, dependency on single method (survey) for data collection may lead to a collection of limited data. As the study focuses on the use of social media, it may be necessary to analyze influence of behaviors and attitudes, for which qualitative methods such as interviews may be effective. The future research in this context can focus on collecting the perspectives of the general population on the use of social media for healthy diet management, increase sample size in the survey, and adopt mixed methods such as survey and interviews for collecting data from different samples for analysis from various perspectives.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by The Institutional Review Board of the Imam Abdulrahman Bin Faisal University. The patients/participants provided their written informed consent to participate in this study.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.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.


By providing the teachers' perspectives, a better understanding of the complexity of RSM in PE may be possible. The results from both the survey and interviews suggest that teachers employ multiple strategies: from safety procedures, complying to compulsory risk measures, to the use of common sense in their RSM practices. The interviewees, on the other hand, initially claim that their RSM practice is quite scarce and, in some respects, not appropriate for PE. They emphasize measures that cater to the students' needs and modification to physical activities in their teaching. However, the interview data suggest that teachers do not primarily conceptualize this part of their practice as RSM but as measures of other pedagogical concerns. Combined, the results from both the survey and the interviews may characterize a RSM practice that relies on teaching experience and the use of discretion. The results in this article both converge and diverge and emphasize the importance of multiple data sources in investigating teachers' RSM practices.The aim of this article is to explore and understand teachers' risk and safety management (RSM) practices in physical education (PE) programs in Norway. A survey questionnaire and semistructured interviews were therefore used to generate quantitative data on trends from a larger sample of teachers ( The inherent element of bodily movement in school physical education (PE) programs generates a risk for accidents and physical injury to students. The ways teachers practice risk and safety management (RSM) in PE clearly inflict on students' educative opportunities. In the UK, for example, former school safety policies and teachers' fear of liability restricted children's development; educators were therefore given an updated mandate to balance educational risk through risk–benefit assessments and the use of common sense  respondents to the survey, 251 (n = 251) were excluded because they had not filled any demographic data or finalized the questionnaire by clicking “finish.” The number of respondents included in the analysis was 698 (n = 698). As there are no current records of the number of PE teachers in Norwegian schools, additional drop-out statistics are not available. Albeit the sample size is considered to be fairly large (n = 698) in a Norwegian PE context, it is not a randomized sample and the results are not generalizable to the population. The respondents still represent all Norwegian counties in 2019 (n = 18); they teach in primary (49%), lower secondary (34.1%), and mixed schools including both primary and lower secondary level (16.6%). There is almost an equal gender representation  among the respondents. Almost half of the respondents (49.9%) have worked 9 years or less as PE teachers. Beginner teachers comprise 117 respondents (16.8%) who had 2 years or less of PE teaching experience, while 31 respondents (4.4%) had more than 30 years of experience.A list of Norwegian primary and lower secondary schools was provided to the researchers by the Norwegian Directorate of Education and Training. In seeking PE teachers who work in public schools who apply the national curricula and regulations for PE, 2,572 schools were contacted to recruit respondents. From the initial number of 949 (Select Survey and multiple steps were taken to develop the instrument according to the study's aim and research questions.The survey instrument was designed by the researchers as an online questionnaire using n = 12). Conversations with representatives from both educator groups as well as opinions on topics and missing and redundant items and values provided information on the face and content validity of the instrument. Their feedback was used to develop and refine the questions and sub-items, and if the clarifying sub-texts were appropriately understood. In addition, based on their feedback about time spent on completing the survey, the survey scope was further adjusted. These steps were then followed by in-depth semistructured interviews with PE teachers (n = 17). Data from this study, including the teachers' wording and the topics that were brought up in the conversations, also helped validate the content and in developing and refining the instrument's questions, sub-items, and values to fit with the Norwegian context. The final survey comprised four main topics: background, experience and opinion, change and development, and practice relevant to this study.First, former research and academic literature on RSM in PE were conferred to gain insight into current knowledge of RSM practices in the field and RSM advice for PE teachers  how often is your risk and safety work part of the following?: teaching preparations, integrated in the teaching, and in the follow-up after teaching (timing of practice) on a seven-point Likert-type scale with increasing values from 1 (never) to 7 ; (2) to what degree are the following elements (shown in content of practice), with eight sub-elements reported on a seven-point Likert-type scale from 1  to 7  including the mid-point 4 (neither/nor); (3) describe your risk and safety work by taking a stand to the statements under (shown in description of practice), with six statements on a five-point Likert-type scale including the mid-point 3 (neither/nor); and (4) are there any physical activities or teaching methods you exclude from your teaching due to risk for injury and accidents? (exclusion of activities), reported on three open response options, whereas the first of the three open response options is presented in this article.In this article, the following four questions from the survey topic shown in  part of shown in  (descripn = 17) primary and lower secondary teachers from eight public schools of different sizes, situated in both rural and city areas in three counties in Norway. A purposeful sampling strategy  content of practice, and (3) description of practice. The data reported on (4) exclusion of activities were categorized with the use of Microsoft Excel by the first author before the categories were cross-checked with the second author and then summarized. The survey results presented in this article are the respondents' assessment and reports on these questions.This article reports on the survey respondents' demographic data and descriptive statistics of four questions related to RSM practice. IMB SPSS software version 26.0 was used to calculate frequency, percentages, means, and standard deviation on (1) in vivo line by line  facilitating and modifying physical education, and (3) conflicting considerations—and are presented in the Results section.Concerning the interviews, the analysis was conducted by the first author. The analytical process began in the interviewing phase and notes were written down during the interviews and while transcribing the material. The coding of the interview material was inspired by a grounded theory approach to emphasize the participants' voices and the empirical data Charmaz, . The matCharmaz,  in the sCharmaz,  were seln = 2,572) that were contacted by e-mail with information of the study and a link to the survey.For both the survey and the interviews, school management functioned as door openers Lindsay,  by forwatiming of practice, (2) content of practice, (3) description of practice, and (4) exclusion of activities and three categories from analysis of interviews: (1) managing risk in physical education, (2) facilitating and modifying physical education, and (3) conflicting considerations.The survey and interview results are presented separately in succeeding sections. These include reports on the four survey questions: (1) To explore when, during their work days in relation to teaching PE classes, teachers practice RSM, the respondents were asked how often their risk and safety work is part of the teaching preparations, integrated in the teaching, and in the follow-up of PE classes.M = 4.6, SD = 1.521). However, only 13.6% report that RSM is always part of the preparations. Then, again, there are also teachers (3.7%) who never include RSM as part of their preparations. A picture of RSM as an integrated practice is drawn as it is reported to be even more frequently integrated in the teaching of PE classes . There are more respondents who report that RSM is always (18.5%) or very often (15.0%) integrated in the teaching than in the preparations. The results here, on the other hand, differ for RSM as part of follow-up in teaching PE classes, as fewer respondents report that RSM is often, very often, or always part of the follow-up . To provide an illustration of teachers' reports on the timing of practice, The results shown in To gain insight into what teachers do in terms of the content of teachers' RSM practices, the respondents were asked to what degree eight content sub-elements shown in  are partM = 5.99, SD = 0.981), supervising students , facilitating activities for the students , and follow-up on rules . The elements that are more remote from the active teaching, especially developing plans and systems , are to a lesser degree reported to be in the content of teachers' RSM practice. To gain a more comprehensive picture of teachers' RSM practices, the respondents were asked to describe their RSM.The results shown in M = 4.51, SD = 0.708) than teachers' use of selected method sets . In more detail, most respondents (93.1%) slightly or completely agree with the use of discretion and common sense in their RSM. This is interesting compared with the use of selected method sets, where quite a few seem to neither agree nor disagree (36.5%), but there are still quite a few who slightly agree (29.8%). This general picture seems to match teachers' agreement of RSM based on experience  rather than RSM as learned from education and courses . Most respondents (88.9%) slightly or completely agree that RSM is based on experience from teaching, and there are more teachers (14.7%) that completely or slightly disagree that their RSM is mainly based on education and courses. In addition, more teachers seem to agree about the activities taught to determine the (RSM) work  rather than being a more general approach reported as work independent of activities taught . Regarding the activities taught to determine teachers' RSM, most respondents (91.8%) slightly or completely agree to this statement. However, these reports fairly coincide with (RSM) work as independent of activities taught, as approximately half of the respondents (48%) slightly or completely disagree.When the teachers were asked to describe their risk and safety work by taking a stand on the six statements shown in As the PE literature points to risk aversion and considering that teachers' RSM practices might relate to the physical activities taught in PE classes, the respondents were asked if there were any activities or teaching methods they excluded from their PE teaching due to the risk of injury and accidents. In reporting on the potential activities or teaching methods that teachers excluded from PE, managing risk in physical education, (2) facilitating and modifying physical education, and (3) conflicting considerations. The excerpts selected serve as examples of category meaning. The codes used in the excerpts  are based on Interview Person and a number given to each participant.The following three categories from the interviews with teachers are presented in the next sections: (1) Teachers in this study initially express a general lack of RSM practice, and they are divided in their explicit use of any risk measures and in the attention they give to RSM in PE. However, when they are asked to describe their RSM practices, the participants consistently begin with and bring up water activities and gymnastics where they apply RSM plans or procedures to their teaching practices. This includes, for example, safety principles for spotting jumps on trampolines or organizing lessons in water in a specific manner.We took a course [in outdoor swimming], and we think about safety a lot, how we are to conduct it for those who are on land and those who are in the water. We never have groups larger than eight at the same time, we always have two [teachers], one teaches and one watches, there are two more [teachers] on land who guard those [students] on land, and we make boundaries for the area in the water with ropes and on land with cones (IP3).Hence, the part of the teachers' RSM practice that are drawn on procedures are commonly applied to physical activities that are perceived to be riskier or more dangerous for the participants in this study. However, the teachers still describe limited system approaches for RSM in PE in their teaching and in their schools. Exceptions are made for a few externally mandated requirements in certain areas of PE as they are compelled to file reports following student injuries and partake in an annual safety inspection of equipment, materials, and facilities. The system of controlling and documenting potential deficits might be ceremonial to teachers becauseif [the equipment] is not replaced, it has at least been recorded in a document (IP14).Against the backdrop of these formalized RSM requirements, field trips, and sporting and recreational events signify a shared customary routine established among the teachers in their schools. Theytalk about it every year, who should walk in front, who should walk behind [the group] and who should carry the emergency kit (IP14).However, the material suggests that PE teachers worry about the pulverization/shredding of responsibility for these events because of the number of teachers involved and they personally are not necessarily in the lead or in control of what happens. The way teachers perceive or frame RSM in PE is central to the results because an impression is made of RSM as comprising of procedural and formalized measures for risk control. Considering that RSM might be a formal practice to these participants, their practice that are pertinent to other pedagogical concerns might still make an essential contribution to their RSM practice.As their framing of RSM might be oriented toward plans and procedures, RSM is portrayed as difficult or even meaningless to implement in PE in some respects. Regarding RSM training, a participant does not seem to find it applicable for PE, and as a result,it would be hard to be trained. I do not see what it should have been—gymnastics yes, because then your back and neck are central, but in most other activities the whole body is used, in a different way.… It would have been terribly interesting. I wonder what that course would have been like if let us say you have ball activities, dance or outdoor education (IP17).As indicated in the above excerpt, the participant includes gymnastics as appropriate for a defined risk strategy while excluding other physical activities to fit the same approach. When the participants are asked to go into more detail about their teaching, they talk about teaching principles and pedagogical and didactical deliberations. Mastery, students succeeding, learning, and having fun in PE classes are given as reasons for adjusting and modifying the program, and not risk.During the conversations, however, the teachers in this study became more verbal and explicit in connecting this part of their teaching practice to risk concerns. These incorporate adaptations of the curriculum, selecting, and adjusting physical activities and sports to the teachers' preferences and the local context, including modifying the activities taught in the PE program to fit with the students' characteristics. The teachers talk of both the need to reduce risk in some respects and the need to facilitate students' learning. Combining strategies is performed by conducting both risk analysis and modifications to physical activities as indicated by a participant in the next excerpts.One must always perform a risk analysis. In natural science, for example, following the principle that if you do an experiment you must do it at the lowest level possible, you do not start with hydrochloric acid if citric acid does the same trick. I think in the same way about PE; you must consider what you want to achieve, and then you must take risk into the whole picture if something can happen (IP1).It is not a homogenic group. They are not athletes. There are people of 40 and 100 kilos. It is rare that you see those gatherings [except in PE]. You must always choose physical activities that you can adapt to all (IP1).The modifications to the program are thus made in accordance with the students' characteristics at an appropriate level of difficulty or variant of physical activities taught. Knowing the students well, therefore, seems to be key for teachers' opportunities to make these adjustments in the programs.I see and observe and feel and talk with the students and determine their limits, each single student in a way (IP10).For teachers to facilitate and adapt their PE classes to the students' characteristics and needs, knowing the students is of utmost importance. Part of the teachers' RSM practice involves the students in risk judgments and makes students responsible for their behavior. A participant also had a strategy of making students feel responsible for what might happen in class by telling them of unsuccessful stories and about the responsibilities of teaching. This includes talking about possible scenarios, what is important for safety in PE and teaching students how to behave toward others. Verbal reminders and addressing students' consciousness and conscience seem to be part of teachers' RSM practices. Establishing rules of conduct is also an appreciated strategy among teachers because students seem to respect the rules when they know of the potential risks involved. Thus, two branches of strategies seem to develop and incorporate teaching students how to be responsible and then make them aware of teachers' responsibilities and the risks involved. Teachers portray this to be part of students' character building and learning in PE and argue that it is part of teachers' mandate and the curriculum. A reference to outdoor education is made to explain the logic.As a teacher, I must have enough knowledge about it to teach students to understand that they are also resources, that we have to take active responsibility during outdoor field excursions, be a resource. Students need to be aware that when they go on their own excursions, they have to be the person who would have to save their friend (IP1).There is also a strategy of protection of girls from a grouping of rough boys which is the reason for separating genders in the data. It is not used as a general or permanent solution among the teachers, but rather,in some of the activities, it is a part of the preparations to ask whether they would rather play girls against girls and boys against boys (IP6).Risk is in one sense dealt with by separation of students, but how cautious boys are considered is not clarified. Rough student groupings might induce teachers to protect other students in PE programs; indeed, there is no addressing of managing the boys' roughness in the data. Regarding dangerous physical activities, however, exclusion seems relevant as a measure.You might cut it out [of the PE program] completely, instead of doing it with a safeguard, you exclude things (IP15).Teachers may therefore eliminate risks by exclusion rather than adapting or modifying the activities taught. This strategy is contended among the teachers due to educative concerns. Although they experience gymnastics to induce risk, some still choose to include it because exclusion might deprive students' development, especially skilled gymnasts. Risk seems therefore to generate conflicting considerations for teachers in PE.Teachers may exclude some physical activities, and there is also resistance toward risk-averse strategies among the participants in this study. In choosing among different strategies, it may, in some respects, for these teachers, manifest itself as a choice between restricting students or accepting risk of injury. Although the participant might be aware of the risk involved, other pedagogical concerns seem to triumph.Often there is a need for splitting the class into groups and to do activities in two halls, and I cannot be in two places at the same time, but [I] still choose to organize the activity in a way that makes it possible to do different things (IP16).Teachers seem torn between educational considerations and the potential adverse consequences of risk. The tension is clear for the participant:If we want to implement some things, it requires a [particular] organization; the risk lives its own life, and then you are in danger of regretting it bitterly if anything happens (IP16).The results are further discussed in the next section, and Zinn's  risk strwhat characterizes teachers' risk and safety management practice in physical education and how do teachers relate their practice to risk and safety management?By combining the quantitative and qualitative data and applying the lens of Zinn's  risk strM = 4.96), make a generous part of their practices. Therefore, the survey results seem to diverge from the interview results in some respects and for which might nuance the first impression. On the other hand, developing plans and systems for preventing injuries and accidents (M = 3.68) is reported to be the least part of the respondents' RSM practices among the categories presented to them  and supervision, observation, and overview of students (M = 5.96), which may signal strategies that are integrated into teaching. Moreover, when the survey respondents are asked to describe their risk and safety work, they greatly agree that they use discretion and common sense (M = 4.51) and that their practices are based on teaching experience (M = 4.34) seen in M = 3.67) and the use of selected method sets (M = 3.46). These survey results seem to converge with the interviews: teachers mainly talk about experience and practical know-how in their practice (Polanyi, timing of practice (What comprise the most central contributions to teachers' RSM practices, reported in Polanyi, . Hence, practice , an abunThen, again, exclusion might be a common risk strategy in PE as teachers in this study do exclude physical activities due to risk. The activities that were mentioned in the survey  and in tHow teachers relate their practice to RSM is therefore central to the investigations and the results in this article. One potential explanation to the interviewees' initial descriptions of RSM as scarce might be found in their framing of RSM and the rationales behind different strategies Zinn, . The matIn teaching physical activities that entail a potential for severe injury such as swimming and gymnastics, teachers make use of preplanned procedures that seem to correspond to rational strategies Zinn, . AlthougThe participants in the interview study also talk about exclusion in relation to something they dread that resonates with emotions as an in-between strategy to deal with risk Lupton, . It mighTeachers' RSM practices might include a willful lack of risk control anchored in their pedagogy. However, educative uncertainty practices in PE (Quennerstedt, In teachers' institutionally framed mandate of school safety, however, it might not be appropriate for teachers to rely on hope, as societal norms and rationales for risk strategies are culturally, institutionally and situationally dependent Douglas, . ConflicBased on the reports from the survey and interviews with teachers, the results suggest that teachers apply and combine multiple strategies with differing risk rationales. Albeit the interviewees may employ preplanned procedures, the results therefrom still indicate that the use of these strategies is limited. However, the survey results suggest otherwise and therefore diverge in some respects. The survey respondents report that plans and procedures and mapping of risk and danger, for example, to be generous contributions in their RSM practices. Central in the results from both the survey and interviews are the predominance of discretion and activity-based measures in teachers' RSM practice. Albeit teachers make modifications and facilitate the program for students, the interview participants do not necessarily conceptualize this part of their practice as RSM. Overall, measures that initially meant to cater to other pedagogical concerns seem to be vital contributions in teachers' RSM practices. However, conflicting considerations might create tension. While teachers' pedagogies may influence teachers to accept risk for educative reasons, safety concerns might influence teachers to exclude certain physical activities from PE.what characterizes teachers' risk and safety management practice in physical education and how do teachers relate their practice to risk and safety management? The multiplicity of concerns and use or combination of risk strategies in teachers' RSM practices presented in this article seem to constitute a complex endeavor. The ways teachers seem to combine different strands of strategy in dealing with risk in addition to other pedagogical considerations in PE might both deviate from and nuance the promotion of what seems to be rational risk strategies in the PE literature on RSM. It more so seems to be a flexible balancing act that resonates with RSM of other professions (Horlick-Jones, The aim of this article was to explore and understand teachers' RSM practices through investigating two research questions: The research that is undertaken is still with limitations and there are multiple avenues for further research to generate knowledge of teachers' RSM practices in PE. As this study is conducted in a Norwegian PE framework, there might be both similarities and potential differences between teachers' RSM concerns of practices in an international context. It is necessary to consider the Norwegian context of PE including the national curriculum and teachers' performance of the curricula. Although the study provides data from both interviews with teachers and survey results on teachers' RSM practices, observation studies may complement, and add to teachers' practice perspectives. To what extent it is possible to prevent incidents, accidents, and injuries while securing students' educative opportunities if teachers made changes to their RSM practices remains uncertain. In addition, giving voice to the students' perspectives on RSM in PE and teachers' practices are relevant for developing RSM but also theory grounded in the students' perspectives. Thus, how teachers may develop their RSM practices to deal with risk and uncertainty in PE seems relevant for intervention studies. Shedding light on teachers' institutional environments and how they influence their RSM practices in PE seems equally relevant, as risk practices are not constructed or performed in vacuum.lise.porsanger@ntnu.no.The datasets presented in this article are not readily available because the data cannot be shared for privacy restrictions. Requests to access the datasets should be directed to The studies involving human participants were reviewed and approved by Norwegian Centre for Research Data. The patients/participants provided their written informed consent to participate in this study.LP designed the study, performed the data collection, analyzed the data, and wrote the manuscript. LM contributed to the design, to the analysis of the survey results, and to the writing of the manuscript. All authors contributed to the article and approved the submitted version.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.


Worldwide, the ocurrence of acute subdural hematomas (ASDHs) in road traffic crashes is a major public health problem. ASDHs are usually produced by loss of structural integrity of one of the cerebral bridging veins (CBVs) linking the parasagittal sinus to the brain. Therefore, to assess the risk of ASDH it is important to know the mechanical conditions to which the CBVs are subjected during a potentially traumatic event . Recently, new studies on CBVs have been published allowing much more accurate prediction of the likelihood of mechanical failure of CBVs. These new data can be used to propose new damage metrics, which make more accurate predictions about the probability of occurrence of ASDH in road crashes. This would allow a better assessement of the effects of passive safety countermeasures and, consequently, to improve vehicle restraint systems. Currently, some widely used damage metrics are based on partially obsolete data and measurements of the mechanical behavior of CBVs that have not been confirmed by subsequent studies. This paper proposes a revision of some existing metrics and constructs a new metric based on more accurate recent data on the mechanical failure of human CBVs. Road traffic crashes and their sequelae are a major problem of Public Health . Every yrisk indexes, also called injury metrics, from which the probabilities of injury or mechanical failure in different structures of the brain can be calibrated. This is the approach followed in this article. Injury metrics can improve the design of restraint systems and can provide reference values for limits in vehicle regulations [Within the automotive industry, a common approach to mitigate TBI occurrence has been the inclusion of passive and active safety systems, as well as the improvement of restraint systems, to minimize the accelerations and stress to the body in a traffic collision. Different crash tests, as well as finite element models, were used to assess the effectiveness of these countermeasures. Specifically, in the research of the effects of road collisions, the so-called finite element head models (FEHMs) have been used ,9. FEHMsulations .For these injury metrics to make accurate predictions, more and better constitutive models are needed for the mechanical behavior of tissues. Moreover, accurate empirical data are needed to establish the physiological ranges of strength of anatomical structures located inside the head. Such data can only be obtained by direct mechanical testing on biological tissue specimens.In this article, we will focus on some of the most widely used injury metrics to assess the probability of ASDH occurrence. Statistical analysis will lead to propose an improvement of existing metrics and even a new injury metric based on more recent data and with higher accuracy than the data available when some of the initial injury metrics were proposed. In addition, it will be shown along the paper, that there are new usable data to improve predictions about the occurrence of ASDH for traumatic events. This improvement in prediction could be used to improve vehicle regulations and restraint systems in order to have an impact on public health: regulatory changes in vehicle safety systems and improved design of restraint systems, would reduce ASDH figures associated to road traffic crashes.For this study, previously published data of human cerebral bridging veins (CBVs) obtained by the authors themselves  and by oFor moderate strain rate, the data were previously obtained by the authors themselves from tensile tests of CBVs. These specimens were dissected from different sections of the meningeal-cortex space, obtained from nine autopsies of post-mortem human subjects (PMHS) conducted in the Forensic Pathology Service of the Legal Medicine and Forensic Science Institute of Catalonia For high or very high strain rate, the data published by Monea et al.  were useAn injury metric to assess TBI is a real-valued functional which depends on the linear acceleration of the skull empirical metrics and analytical metrics. Empirical metrics are simpler and can be computed from purely kinematic data, while analytical metrics compute an injury measure based on simulated strain or stress in tissue structures, by means of an adequate FEHM. In this article, we compare three analytical injury metrics and their predictions for a computational dataset calculated using the SIMon model, a FEHM developed by Takhounts and coworkers [In practice, two types of injury metrics are commonly used for injury prediction: oworkers ,14.In addition, there are some mathematical properties that make a metric suitable, which we will examine for the three metrics. As a mathematical functional, the suitable properties of an injury metric are scalability, continuity and convexity  see App. ScalabiThe occurrence of ASDHs associated with traumatic events is clearly correlated to the mechanical failure of cerebral parasagittal bridging veins (CBVs). The mechanical failure of a blood vessel of this type generally causes a major hemorrhage in the meningeal-cortex space, resulting in an ASDH, a potentially life-threatening situation for the subject who has suffered the traumatic event.relative motion damage measure (RMDM), first introduced in 2003 [kth vein, kth strain rate.The most widely used metric for estimating the probability of mechanical failure of CBVs has been the  in 2003 ,16. Thisfunction ,17, and This metric has been extensively used in many subsequent empirical and theoretical studies which showed the usefulness of RMDM for assessing traumatic events ,19,20,21ain rate ,12, contIn fact, it is important to note that, after Löwenhielm’s work, a good number of published studies of the mechanical properties of CBVs have been done ,23,24,25As mentioned before, RMDM used the idea that excessive stretching along the longitudinal direction of a CBV was the cause of its mechanical failure. Furthermore, a conjecture on how ultimate strain decreases with increasing strain rate in Löwenhielm’s empirical data ,17 led tain rate ,25, and alue see .i-th CBV :The above reasoning allows us to construct a risk index for a single CBV. However, in the brain there are more than a dozen of CBVs, and to assess the possibility of a ASDH would require an analysis of the probability that at least one vessel connecting the parasagittal sinus to the brain presents a mechanical failure. In a traumatic event in which the skull and brain undergo large accelerations, the probabilities of failure of the different CBVs are not independent, because the axial forces experienced by the veins depend on the global forces produced in the interaction of the whole brain and skull. Although if we know the forces to which each individual CBV is subjected, a common situation in FEHM simulations, then it turns out that the conditional expected values data see , the val an ASDH:P of this magnitude with strain rate  For this reason, a The first factor extreme value theory (EVT), the Fisher–Tippett–Gnedenko theorem [It is a well-known fact that when examining a population of the same type of force-resistant elements possessing a certain micro-structure, the ultimate stress is often distributed according to a generalized extreme value distribution (GEV distribution). Interestingly, the fundamental theorem of  theorem , has its theorem ,28. Simi theorem ,30,31, w theorem .A the cross-section area of the CBV and the intrinsic ultimate axial force A total sample of Equation . Figure p-values obtained in the goodness-of-fit tests to a Weibull distribution were high, corroborating that the Weibull distribution can adequately represent the data: for the Kolmogorov–Smirnov test the p-value was 0.962 and for the chi-squared test =Pn independent CBVs is easy. The problem was discussed in p-norm of the intrinsic axial forces:Once the probability of mechanical failure for an individual CBV is known, the problem of finding an injury metric that considers the possible damage in This formula is proved in It is clear that BVDM is a scalable and continuous function. Moreover, in the sense of . As for In order to compare the above metrics . For the case of the ultimate intrinsic axial force, this probabilistic analysis leads to an injury metrics that is a scalable, continuous and convex function of the forces, that is particularly simple , as the experimental failure data seem to be given by a Weibull distribution.Another interesting point of our analysis is the distinction between local risk (failure in a specific CBV) and global risk (failure in any of the existing CBVs). Since any of the This combination of individual risks in the overall aggregated risk is important, since, in addition to SIMon FEHM which includes 7 element pairs for the CBVs, most recognized FEHMs use multiple elements to model the CBVs. In this sense, the KTH FEHM (S. Kleiven)  uses 11 In addition, a comparison of the overall risk calculated using RMDMA limitation of the empirical data used is that viscoelastic effects in CBVs have been insufficiently studied . MoreoveFor these reasons, further work is needed to corroborate whether in mechanical tests with PMHS the BVDM that frequently predicts a higher risk than the RMDM for low strain rate could outperform the metrics currently in use. At the present stage and based on experiments on isolated CBVs, it is not completely sure to say that BVDM will perform better than RMDM, even if it is based on recent measurements and with lower measurement errors.The number of ASDH occurrences due to road traffic crashes constitute an important Public Health issue. Although the usual approach of automotive industry based on injury metrics seems well founded from a theoretical point of view, it should make use of most recent data on the mechanical properties of CBVs, because the measurements in more modern tests are more accurate. Specifically, the injury metric most commonly used to predict ASDH is based on old data that subsequent research does not seem to have validate. Therefore, FEHMs are very helpful to figure out whether a metric based on more modern and accurate constitutive model data is better than the old ones. Here, the BVDM has been proposed to make more accurate predictions, and providing an additional guide for the design of restraint systems.This paper explains how to use modern data to find intrinsic forces and stress, independent of strain rate, which can be used to construct a new injury metric that satisfies the reasonable mathematical requirements for any injury metric. All these improvements could play a role in vehicle regulations that would eventually reduce the percentage of more serious TBI cases in which ASDH appears as a consequence of road traffic crashes.


In the last couple of decades, there has been a lot of interest on the impact of macroeconomic fluctuations on health and mortality rates. Many studies, for different countries, find that mortality is procyclical. However, studies examining the effects of more recent recessions are less conclusive, finding mortality to be less procyclical, or even countercyclical. In this paper, using data of Spanish provinces from 1999 to 2016, we investigate how this relationship works in the context of a country that is subject to extreme business cycle fluctuations. Furthermore, we analyze the impact of unemployment for different mortality causes and we explore differences by sex, age group and level of education. In general terms, we find mortality to be procyclical so that when the economy is in a recession, mortality falls. When exploring mortality causes, we show that deaths from cardiovascular disease, cancer, senility, transport accidents and homicides are procyclical. By sex, we find procyclicality for both men and women. By age, mortality is procyclical for all age groups; however, the causes of death that result in this procyclical behavior are specific to each age group. By educational level, suicide appears as a countercyclical cause for individuals with intermediate levels of education. There is a widely interest among social science researches and policymakers in understanding the relationship between macroeconomic fluctuations and health, with a particular focus on mortality.Aggregated time-series data by Brenner , 2 disclIn the last couple of decades, many studies have attempted to replicate these findings with the aim of understanding the specific causes that could explain this relationship using multiple techniques and datasets. However, the results of this large literature show ambiguous conclusions: on the one hand, there are many papers supporting the idea that mortality rates decrease during temporary economic recessions , 23, 24 In 2008 Edwards  pointed Another more recent paper that explore the opposite-direction effects of contextual and individual unemployment on mortality is Tapia Granados et al. . They shThe recent recession that affected the global economy in 2008 marked a new opportunity to study this relationship. The new wave of papers looking at the relationship between mortality and business cycle conditions find even more diverging conclusions: some authors point towards a reduction in the previously documented procyclicality when using post-2008 data as compared to papers using pre-2008 data , 14, 17 Ruhm  suggestsNonetheless, the factors explaining the divergence of findings in the literature are not entirely clear yet. Some authors have provided some examples: Ruhm  suggestsOur paper contributes to this literature by examining the relationship between macroeconomic conditions and mortality in Spain, a country that has been severely hit by the recent economic crisis. Using very rich administrative data  covering the period 1999–2016, we link local  level unemployment rates to local level mortality rates while controlling for the age structure of the population, regional and time fixed effects, as well as regional trends. The strong variability in business cycle conditions over time in Spain , To analyse the relationship between macroeconomic conditions and mortality rates, we follow very close Ruhm . Our depk resulting from a one percentage point increase in the unemployment rate. These relative effects are translated into absolute numbers through estimates of:k and D is the average annual number of deaths .To estimate the relative effects we can estimate, following the same idea than Ruhm :\documenIn particular, we estimate Eq  for the We consider 52 geographic units that, for simplicity, we call provinces. However, strictly speaking what we include corresponds to 50 provinces plus Ceuta and Melilla, that are autonomous cities. All regressions are weighted by the squared root of the population in each geographic unit and time, and standard errors are clustered by geographic unit.As an indicator of macroeconomic conditions, we use the unemployment rate. We obtain annual and quarterly unemployment rate information for each province from the National Institute of Statistics in Spain (INE).We use mortality registers for the period 1999–2016 also from the INE. The restricted access version of the files allow us to include information on the type of diseases that caused the death. The registers are collected at the individual level and include all deaths in Spain from 1990 to 2016, the diseases that caused the death and some individual characteristics such as sex, age, education and province of the person that died. We collapse the individual information by province for each year to get the number of individuals dying in each province and time period. We aggregate the information for total mortality but also for different causes of death. To do the analysis of cause-specific mortality we classify the different mortality causes in 12 categories: cardiovascular, cancer, respiratory, senility, Alzheimer, diabetes, digestive, other diseases, transport accidents, other accidents, suicides and homicides. To calculate mortality rates, we divide the number of deaths by the population (and multiply it by 1000), using information on population numbers in the same province and year.In addition to total annual mortality rates for each province, we construct sex-specific death rates, mortality rates for five age groups , as well as by level of education for those aged over 25 years old (we only have information about education from 2012 onwards).Table Table Figure In the first row of Table In the following rows of Table In the last two rows of Table Table A second exploration exercise that we are interested in this article is to analyse the differences in the cyclicality of mortality by age group. As we explained in the descriptive section, we have five age groups . In Table In Table A third heterogeneity exercise that we implement distinguishes across different levels of education. We classify individuals according to the highest level of education that they have obtained. As we only want to include those individuals that have already completed their desired level of education, we restrict the sample to those aged over 25 years old. Unfortunately we only have this information from 2012 onwards. In our dataset, we can distinguish between five education levels: less than primary school, primary school, secondary, high school and university. As we can see in Table Finally, an important exercise is to calculate how much these coefficients represent in terms of the number of deaths. Table This paper shows that, during the period 1999–2016, mortality exhibits a procyclical pattern in Spain; that is, when the local unemployment rate increases mortality falls. Exploring the impact of unemployment for different mortality causes we show that deaths from cardiovascular disease, cancer, senility and transport accidents are strongly procyclical. However, countercyclical patterns have emerged for diabetes and suicide.When we study the effects by sex, we see that, for both men and women the coefficient is negative  although the effects for men are somewhat higher. Again, cardiavascular, senility and transport accident causes seem to lead that procyclicality. Mortality is procyclical for all the age groups analysed; however, the causes that foster this procyclicality are slightly different in each age group. For example, for those between 45 and 65 respiratory problems and transport accidents explain the procyclicality pattern. On the other hand, procyclicity of deaths due to cardiovascular problems appear in a significant manner in all age groups (except those of 25–45). By educational level, suicide appears as a countercyclical cause (increasing in recessions and decreasing in the growing seasons) for individuals with intermediate education levels.We believe that our paper provides new evidence on the relationship between business cycle conditions and mortality with respect to the previous literature. More specifically, our data allows us to study this relationship for a more recent period and for a country that has been exposed to an extremely strong recession in the mid-2008. With respect to the article of Tapia Granados , we are Compared with Regidor et al. , 14 our


Depression is one of the most frequent and severe psychiatric conditions. Many chemical drugs to treat depression are associated with adverse reactions and have shortcomings. Traditional Chinese medicine is of great significance in the prevention and treatment of depression. Xiaoyao pills has achieved good results in clinical application, which has the advantages of quick effect and no obvious adverse reactions. The aim of our study is to evaluate the efficacy and safety of Xiaoyao pills on mild to moderate depression patients.This study is a multi-centre, double-blinded, randomized and placebo-controlled clinical trial. A total of 108 participants are assigned to three groups: Xiaoyao pill group taking Xiaoyao pills twice daily for 4 weeks, placebo group taking placebos twice daily for 4 weeks and normal group without taking any drug. The primary and secondary outcome measures are the Hamilton Depression Scale (HAMD) and Traditional Chinese Medicine (TCM) Syndrome Scale. The assessment is at baseline (before treatment initiation), 1 week, 2 weeks 4 weeks after the first treatment. Exploratory outcome is also assessed to explore the mechanism of Xiaoyao pills at baseline and 4 weeks.The results from this study will provide clinical evidence on the efficacy and safety of Xiaoyao pills in patients with mild to moderate depression with syndrome of liver stagnation and spleen deficiency.ClinicalTrials.gov ISRCTN12746343. Registered on September 25, 2020. Depression is one of the most frequent and severe psychiatric conditions, with an estimated prevalence reaching 15% in the general population . DepressTraditional Chinese medicine (TCM) is of great significance in the prevention and treatment of depression. Xiaoyao pills, which is one of traditional Chinese medicine prescription, have been used for both the prevention and treatment of chronic dizziness for thousands of years. It has achieved good results in clinical application, which has the advantages of quick effect and no obvious adverse reactions . XiaoyaoThis study intends to carry out a multi-center randomized controlled and double-blind trial to observe the efficacy of Xiaoyao pills in the treatment of mild to moderate depression.This study is a multi-center, double-blinded, randomized, placebo-controlled, parallel group and exploratory clinical trial with allocation radio 1:1. The trial protocol has been approved by the ethical committee of the Beijing University of Traditional Chinese Medicine (ref: 2020BZYLL0304) and is registered with ISRCTN at Current Controlled Trials (ISRCTN 12746343). The patients are provided with written informed consent. The trial is based on the principles of ICH-GCP  and apprA total number of 72 participants with mild-to-moderate depression (referred to symptoms of liver stagnation and spleen deficiency) and 36 healthy participants are recruited at the five trial sites in china, including Peking University Sixth Hospital, the First Affiliated Hospital of Jinan University , the Affiliated Brain Hospital of Guangzhou Medical University, Dongfang Hospital , and Beijing Anding Hospital Capital Medical University. Participants are informed of details about the study which are purpose, duration, procedures, and key contacts, as well as risks and potential benefits. Participants may withdraw their consent for any reason without any consequences at any time. Eligible 72 participants with mild-to-moderate depression are randomly allocated to Xiaoyao pill group Group 1) and placebo group (Group 2), who are required to take Xiaoyao pills and placebos, respectively, twice daily for four consecutive weeks. 36 healthy participants are allocated to the normal group (Group 3) without taking any drug. The flow chart is listed in Fig.  and placParticipants meeting the following criteria are included:1. Meet the Diagnostic Statistics Manual of Mental Disorders (DSM-5) regarding the diagnosis of mild to moderate depression;2. A score between 20 and 35 on Hamilton Depression Scale (HAMD);3. Meet the TCM criteria of liver stagnation and spleen deficiency syndrome;4. Aged between 16 and 18 years old;5. Patients agree to participate in this trial and assign the informed consent;6. Capable of reading and follow-up treatment, and permanently live locally.Participants meeting one or more of the following criteria are excluded:1. Bipolar depression, treatment-resistant depression, and severe suicidal risk;2. History of bipolar disorder, schizophrenia, obvious psychotic symptoms, and depression disorder caused by non-addictive substances;3. Combine with severe cardiovascular diseases, cerebrovascular diseases, hepatic diseases, renal diseases, hematological disease, cancer, or other severe primary diseases;4. Pregnant or lactating women;5. Inability to finish the compliance test, judge the efficacy, and have complete data;6. Involved with any other clinical trial at the time of consent.All participants with depression enrolled in the study as well as 36 healthy people sign a paper version of informed consent prior to study initiation. The recruitment of participants in each study centre is made by the researchers (doctors) in each study center. Researchers make face-to-face evaluation of patients or healthy people who are willing to participate in the project. If the participants meet inclusion criteria, the researchers inform them to sign the informed consent. Only after signing the informed consent can the trial process be officially started. Two copies of the informed consent were kept by the researchers and the participants, respectively.Standard clinical laboratory findings  as indicators of safety evaluation are routinely collected before and after the enrollment of patients to ensure the safety of subjects. Participants’ urine samples and blood samples are monitored by liquid chromatography-mass spectrometry (LC-MS) technology to explore the mechanism of action of the metyrapone at baseline and at 4 weeks. At the same time, participants’ blood samples are used to separate the total RNA. The study participants have given consent for their blood samples and data to be used. The ethics committee has given consent to the trialists to conduct the study. All the samples required for the study do not need to sign additional informed consent, because the committee has already been approved by the ethics committee and can use the data after signing the informed consent.The placebos were manufactured by the Jiuzhitang Co., Ltd. Placebos are similar to the physical traits of Xiaoyao pills in size, flavor, scent, and color without the key ingredients. The placebos are composed of corn starch, pregelatinized starch, maltose, caramel color, and water.Participants randomized to treatment Group 1 take Xiaoyao pills, which are composed of ChaiHu (Radix Bupleuri)-100g, DangGui (Radix Angelicae Sinensis)-100g, BaiShao (Radix Paeoniae Alba)-100g, BoHe (Mentha)-20g, ShengJiang (Ginger)-100g, BaiZhu  - 100 g, FuLing (Poria cocos Wolf) -100g, and ZhiGanCao -80g. The action and batch number of each herb are summarized in Table Cases that have been enrolled but do not complete the clinical protocol should be considered drop outs in the following circumstances:1. Patients withdrew from the trial on their own;2. Lost to follow-up;3. Poor compliance;4. Because some diseases are considered by the study physician to be amenable to withdrawal from the trial.The case should be explained. If the baseline pharmacodynamic data are available, the results of the last major outcome can be transferred to the final result for statistical analysis, and the research records should be kept for reference.The entire trial is completely stopped in multi-centers for the following reasons:1. Serious safety concerns identified by the investigator;2. There are major lapses in the trial;3. Reasons for funding or management by the sponsor;4. The administrative department cancels the trial.Total discontinuation of the trial can be temporary or permanent. When discontinuing a trial, full trial records should be retained.Cases that have been enrolled but meet one of the following should be removed:1. Cases were incorrectly diagnosed and incorrectly included;2. Met the exclusion criteria;3. One medication was not used;4. Without any test record;5. Due to the use of some prohibited medication, it was not possible to evaluate drug efficacy.Rejected cases should state the reason, and their original medical records should be retained for statistical analysis of efficacy.Clinical research coordinator is set up to guarantee subject compliance. Drug record cards are also distributed to allow patients to record their medication status and follow-up time.1. Avoid cold and greasy foods that are difficult to digest.2. During the period of taking the medicine, keep optimistic, and avoid getting angry.3. People with severe chronic diseases such as high blood pressure, heart disease, liver disease, diabetes, and kidney disease should take it under the guidance of a physician.4. Normal menstruation, sudden excessive menstrual flow, prolonged menstrual period, or oligomenorrhea, wrong menstrual period, or irregular vaginal bleeding should go to the hospital for treatment.5. People who are allergic to this product should not use it with caution.6. It is forbidden to use this product when its properties change, such as from solid to liquid or packing damage.7. If you are using other drugs, please consult your physician or pharmacist before using this product.There are no expected harms resulting from the trial. After the trial, patients will be provided with guidance on specialized treatment protocols in psychiatry.The HAMD is a tool developed for clinical evaluation of depression and is widely used in studies . It is cTCM Syndrome Scale is used as a measure of depression . It consThe urine and blood of participants are monitored to explore the mechanism of Xiaoyao pills at baseline and 4 weeks by liquid chromatograph-mass spectrometer (LC-MS) technology. Meanwhile, the total RNA is isolated from the blood sample using TRIzol (Life Technologies). Differential expression is analyzed by using the TopHat method. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of differentially expressed genes are implemented by the Methylmion Specific PCR. And the exploratory outcomes are expected by the network pharmacology to conduct the correlation analysis with the differential genes.Participant timeline is shown in Fig. α = 0.05) and type II error (β = 0.1). Meanwhile, taking into account a dropout of 15%, 72 patients are recruited with another 36 healthy persons. Therefore, we calculated the sample size as 108 participants.Based on previous findings of Xiaoyao pills in the treatment of depression , 21, theA total number of 72 participants with mild-to-moderate depression (referred to symptoms of liver stagnation and spleen deficiency) and 36 healthy participants are recruited at the five trial sites in china. The number of registrations at each facility is monitored by the monitoring committee via electronic data capture (EDC). We publish clinical trial information through posters and WeChat public account articles. Posters are posted in various sub-centers and communities. WeChat public account articles are open to the general public. The contact information of the research center and the researchers is found in the posters and articles. At the same time, the researcher also recruits the participants in the outpatient clinic. They evaluate and recruit prospective candidates by introducing the trial to the them. The researcher conducts a face-to-face assessment of the potential participants. And the participants who meet the inclusion criteria are formally included in the clinical trial after signing the informed consent.The study adopts the method of central stratified block randomization. According to the given seed number and segment length, the random number table of 72 subjects is generated by an independent statistician using SAS 9.4 statistical software according to the ratio of 1:1 of the Xiaoyao pills group and the placebo group.In order to make the researchers and participants unable to predict the group of the next participant, we implement the allocation sequence with sequentially numbered, opaque, and sealed boxes. Drugs are put into medicine boxes of the same size and coded in sequence. The coding of all drugs is prepared and taped by a third-party person unrelated to the trial. After the participants are officially enrolled into the group, the researchers distributed the medicine boxes to the participants. Each study center cannot know participants’ information in other centers.The allocation sequence is generated and saved by statisticians who do not participate in the clinical study. The recruitment of participants is conducted by the researchers. Researchers assess whether the participants meet the inclusion criteria. After the participants who meet the inclusion criteria sign the informed consent form, the researchers send the sealed boxes containing drugs and coded in sequence to the participants and unable to know the specific intervention of the participants.The study uses a double-blind design and drugs are coded and packaged blind according to a generated random number table by personnel unrelated to this trial. The drugs in each group are uniformly packaged, while guaranteeing that the Xiaoyao pills and placebos are not different in appearance. The centers dispense the drugs sequentially with the assigned drug number and in the order of subject enrollment. The participants, researchers are blinded to treatment allocation. All participants are informed that they have an equal opportunity for allocation to the Xiaoyao-pills group or placebos group before enrollment. Data analysts and outcome assessors do not participate in the blinding. Clinical trial related data, such as drug types and affiliated centers, is passed to data analysts and outcome assessors after uncovering blinding. The blind bottom is kept in duplicate by the principal investigator and the sponsor after sealing, and the blind bottom could not be removed during the trial.At the end of the trial, the first-level uncovering blinding is performed after checking CRF, EDC, and signature. The groups of subjects are determined by the first-level uncovering blinding to conduct statistical analysis. After the statistics analysis, the second-level uncovering blinding is performed. Through the second-level blinding, the Xiaoyao pill group and the placebo group are determined to evaluate the drug efficacy. Unblinding is generally done at the end of the trial for statistical analysis and outcome assessment. However, in order to ensure the safety of the subjects, the blindness is uncovered in some emergency situations, such as the occurrence of a serious adverse event, unable to judge its relationship with the trial drug, whether it is overdosed, whether it has serious drug interactions with the concomitant medication, etc. When it is urgent, researchers need to know what drug to take to decide the rescue regimen. After uncovering blindness, it is necessary to record the time, reason for breaking the blindness in advance and the person performing the blind breaking, and to notify the inspector and the sponsor as soon as possible. Once the blindness is uncovered in advance, the participants should not continue to participate in the study. The data of these participants cannot be used for the efficacy evaluation analysis, but the data should still be included in the safety analysis data set. And the participants should be treated and protected in time. An emergency letter is prepared for every participant with an envelope made of thick, light tight paper. Unblinding of a single participant should not disrupt the blinding of the entire clinical trial. Emergency letters are made by a third-party person unrelated to this trial.The results and baseline of all participants are collected and evaluated on Electronic Data Capture System (EDC). Assessment and collection of outcome, baseline, and other trial data are performed and recorded on EDC. All data is collected and entered into the EDC system by researchers. The system has data entry range value and character. And the system preliminarily tests the rationality of the data. After the entry, data monitoring committee checks the data quality again. During the course of this study, the sponsor performs regular on-site monitoring visits to the study centers and trains researchers in every study centers to ensure that all the elements of the study protocol are strictly followed and that the data are completed properly. At the same time, a unified case report form, HDS and TCM Syndrome Scale, should be used in every study center. Those researcher in clinical research should be relatively fixed. They should study and discuss the clinical research protocol and the manual of clinical research carefully. The way of recording and the standards of judgment should be unified.A participant follow-up record form is set up for this study, and the follow-up of participants is managed by the clinical research coordinator (CRC). Clinical research coordinators record patients’ enrollment time, follow-up time, dose of drug, and remaining dose of drug at every follow-up time. Clinical research coordinators contact the participants to go to hospital on the follow-up day, and the research doctors evaluate the patient on the follow-up day and distribute drugs of the next phase. Every time the participants go to the hospital, they receive appropriate transportation subsidy. Before joining the project, the patient is promised to receive further treatment guidance from a specialist after the trial. If the subjects drop out of the trial or interrupt the trial, the data of the subjects is blinded with other subjects until the trial is completed. And the data of these subjects is statistically analyzed separately before uncovering blindness and finally are explained separately in the outcome part of this trial.The sponsor collects the paper version of case report forms (CRFs) of patient data for the proper storage as the study raw materials. All data are entered into the EDC, and any traces of entries, modifications, deletions etc. in the EDC are retained in the log showing who and when they were changed. Paper version data are input into the EDC system by two researchers in the sub-center, and double entry is adopted. The electronic data are backed up, and the backed-up electronic data are saved by another person. The sponsor checks the data again according to CRF to ensure the accuracy of the data. The sponsor arranges statisticians to complete the screening and randomization of research data. The paper-based CRF is sent to the sponsor in a safe and sealed way to ensure that they are not lost or leaked in the middle way. And all the paper-based CRF forms and the subjects’ information in EDC system are properly kept by the sponsor.All patients’ data are kept confidential and not disclosed. Only study physicians granted authority by the sponsor have access to the EDC by account number and password and can only enter and review patient data at their site. The statistician and sponsor have access to the data for all participants. The sponsor checks the entered data regularly to ensure confidentiality. Patients’ data are stored in raw medical records at each hospital and anonymized stored in EDC for at least 5 years. Participants are allocated an individual trial identification number and participant’s details are stored on a secure database. Anonymized trial data cannot be shared with other researchers to enable international prospective meta-analyses.After signing an informed consent form, patients are given a baseline blood sample and retention urine sample, in which the blood routine, liver, and kidney function and urine routine are safety evaluation indicators. Meanwhile, a portion of blood samples are used for DNA methylation detection and a portion of urine samples are used for metabolomics detection. These blood and urine tests are performed again when the patient is out of the group.Blood and urine samples are stored properly in −80°C and not be used by any other route than the study. Meanwhile, the existing as well as further sample specific studies will be conducted with ethics committee approval. If there are any remaining research specimens, biological specimens will be allowed to be used for future research in the case of reapplying for ethical approval.P<0.05. Comparisons between groups are conducted by using an analysis of covariance (ANCOVA). The significance of the cure rate, improvement rate, and unhealed rate differences between the groups are compared using ridit analysis and chi-square test.Investigators establish the electronic case into the EXCEL form when making follow-up observations by interviewing the participants. Paper is entered into a database by those investigators in order to ensure data validity. All analyses are performed using SPSS software version 21.0. Differences are considered to be statistically significant for two-sided Security monitoring follows through the study at all times. Adverse events are reported immediately to the principal investigator, who is required to report them to the clinical trial monitoring committee within the prescribed period of time, depending on the severity. The clinical trial monitoring committee decide on a case by case basis whether to terminate the study.No efficacy interim analysis is set up in this study.There will be no subgroup analysis based on gender for example or mile or moderate depression.Participants with missing primary or secondary outcome data are excluded.http://www.isrctn.com/ISRCTN12746343). The datasets analyzed during the current study are available from the corresponding author on reasonable request.This study protocol is registered with the registration number ISRCTN12746343 on the International Standard Randomized Controlled Trial  has an independent chair. In addition, the TSC has two public/patient group representatives, two clinical trials unit directors, statistician, and the principal investigator. If a member of the TSC withdraws during the course of the trial, we identify a replacement with a similar background. The members of TSC meet at the start of the trial and then weekly to review recruitment rates, protocol amendments, and any protocol deviations identified and may make recommendations to the sponsor regarding running the trial.The data monitoring committee is set up by the Beijing University of Chinese Medicine, and its members have no interest relationship with the sponsor. The members should have professional knowledge of medicine, pharmacy, health statistics, and be familiar with relevant laws and regulations of clinical trials. The committee monitors the eligibility, integrity, safety, and effectiveness of data in each research center through EDC system and question the problem data, which can be directly marked in EDC and generate a verification log. The modification traces of data by researchers in each center are also one of the monitoring contents. The data verification function of the EDC system is exclusive to the data monitoring committee, and the sponsor and researcher have no authority to carry out it. The committee also supervises protocol compliance, participant recruitment, and paper version clinical efficacy report every 2 weeks.Once an adverse event occurs, the investigator shall state to the subject that the subject is required to report truthfully the changes in his condition following the medication. Physicians are to avoid inducing questions.While observing efficacy, pay close attention to observing adverse events or unanticipated toxic side effects , analyze the causes, make judgment, and follow-up observations and records.For adverse events occurring during the study period, their symptoms, extent, time of appearance, duration, handling measures, experience, etc. should be recorded on a case report form, evaluated their relevance to the study drug, and recorded in detail by the investigator, signed, and dated.When an adverse event is identified, the observing physician may decide whether to discontinue observation based on the condition, and cases who discontinue because of adverse effects should be followed up with a detailed record of the handling and outcome.In the event of a serious adverse event in a study, the unit that assumes the responsibility for the clinical study must take immediate measures to protect the safety of subjects, must report to the project leader and the Research Center for clinical trials of drugs, should report within 24 h to the drug administration, the subject responsible unit, and the ethics committee. The investigator should also report to the data monitoring committee and relevant regulatory bodies as required indicating expectedness, seriousness, severity, and causality.Investigator should sign and date on report. The subject responsible unit will guarantee reporting procedures that meet all legal and regulatory requirements.When urgent breaking of blinding is required for a serious adverse event to occur in a clinical study, the blinding should be broken jointly by the project leader, investigator, clinical monitor.The sponsor and the study center meet weekly to ensure that the study is being conducted in accordance with the study protocol.If the study protocol is amended, it must be approved by the ethics committee of the Beijing University of Chinese Medicine, and patients are also provided written informed consent to inform the modification. Sponsor and funder are notified first. Then, the principle investigator notifies the centers and a copy of the revised protocol is sent to the principle investigator to add to the Investigator Site File. Any deviations from the protocol are fully documented using a breach report form. The protocol also is updated in the clinical trial registry.The results of this study will be published in a scientific journal.Depression is a common affective mental disorder, which is associated with a high burden of disease. Research suggests that chronic diseases, genetic factors, social, and environmental factors can induce depression . The comAccording to traditional Chinese medicine theory, liver stagnation and spleen deficiency syndrome is one of the main syndromes of depression. Especially due to people’s unhealthy eating habits and long-term emotional stress from life and work in modern society, the symptoms of the liver stagnation and spleen deficiency are very common. In clinical practice, the syndrome of liver stagnation and spleen deficiency has become a high incidence and common syndrome. Xiaoyao pills has good effect of soothing the stagnated liver and strengthening the spleen. In our study, TCM syndrome efficacy evaluation is added in order to determine more suitable patient populations to take Xiaoyao pills and optimize indications.The potential mechanism of Xiaoyao pills to treat depression mainly focused on animal experiments –28. TherHowever, our study has limitation. The limitation concerns the fact that we will only recruit mild to moderate depression patients with syndrome of liver stagnation and spleen deficiency in order to ensure the curative effect. Effectiveness of TCM for different types of depression is not evaluated.Therefore, a clinical trial about traditional Chinese medicine to treat different types of depression are still needed.This study protocol is version 3 made on June 1, 2020. Recruitment commenced in March 2020 at Peking University Sixth Hospital and is expected to be completed in December 2021.The trial is currently in the recruitment phase.