In recent years, a number of government-sponsored initiatives have been implemented in Germany that are focused on early preventive intervention in child protection. In response to the need for interdisciplinary training in this area, the internet-based e-learning program “Early Preventive Intervention and Child Protection” was developed for professionals in the child welfare and health care systems working with families with infants and toddlers. The program is currently undergoing evaluation for effectiveness and user satisfaction.In a pre-post design, users are requested to complete questionnaires that assess three measures of expertise: theoretical knowledge of relevant fields, the ability to correctly identify subtle signals of infant communication, and the ability to assess maternal sensitivity. This article presents the contents of the program and the pre-training results (N = 1.294 participants). Descriptive analyses as well as Pearson correlations and Bonferroni corrections of error were conducted using the statistical program SPSS v. 21.0.The findings show that a wide range of professionals are making use of the program, and that their existing theoretical knowledge about early preventive intervention, as well as their ability to identify subtle signals of infant communication, is relatively good. However, their ability to assess maternal sensitivity, which is considered a crucial indicator for the risk of child abuse, was low.The outcome of the pre-training results indicates that professionals working in the area of child protection need to develop more capability in recognizing maternal sensitivity, in order to ensure early detection of families who are at risk and thus in need of support. Finally, the number of years of professional experience did not correlate with the scores on any of the three measures, which emphasizes the importance of providing interdisciplinary training in this area for all those working in child and family services, regardless of background. Following some tragic cases of child abuse and neglect over the last decade in Germany that received intense media attention, policy-makers, researchers, and professionals who work with children and families became increasingly focused on the causes of child maltreatment and on possible strategies for its prevention. Early intervention is recognized as being especially desirable, as the problem of child abuse is most frequent and has the most detrimental consequences in infancy . ChildreTo foster a preventive support system within the existing structures of health care and child welfare agencies, a number of political initiatives have been implemented in Germany at both the national and local levels. These initiatives were framed by a recently improved understanding of the significance of early preventive intervention and thus commonly called “Early Preventive Intervention”. In 2006, the Ministry for Family Affairs, Senior Citizens, Women and Youth initiated a program titled “Early Preventive Intervention for Parents and Children and Social Early Alert Systems” .Experience with all these initiatives and projects has made it clear that early preventive intervention focused on child protection is a complex and demanding task, and one that cannot be fulfilled successfully through isolated initiatives or single disciplines . AccordiTo achieve this challenging goal, it is clear that comprehensive interagency expertise is required, and that all professionals concerned with child and family care need to acquire a deeper understanding of preventive child protection including early signs of child abuse and neglect, and evidence-based support strategies. Successful prevention efforts rely on interdisciplinary knowledge and on competence at identifying known risk factors and existing warning signs at an early stage, in order to be able to protect children from further experience of violence. Interagency collaboration and networking are prerequisites, and educational programs are required that can provide systematic and interdisciplinary training for all impacted professionals.The early parent–child relationship is a crucial focus in the area of child protection, because the fit between a child’s signals and the parent’s response crucially affects the development of social and cognitive functions . The earOnline training (e-learning) programs are ideal for providing training that is broad, systematic, and easily accessible. Users have complete flexibility with respect to when and where they access a course ; can ind“Early Prevention and Intervention in Child Protection”  is an inBasic information: Interdisciplinary knowledge in the area of early intervention in child protection; e.g., the prevalence of child abuse and neglect, key stakeholders, basics of developmental psychology, risk factors and protective factors, applicable laws, and regulatory frameworks.Manuals: Detailed explorations of specific topics from the basic information section, such as a parent with psychiatric problems, preterm birth, a child with physical or mental disabilities, attachment disorders, and regulation disorders.Methods: Strategies for recognizing the signals that infants use to express their needs and emotions and for assessing a parent’s level of sensitivity to these signals, so that the quality of the parent–child interaction can be determined. This section includes a training tool for the evaluation of a child’s developmental status, and presents video examples to help train the user in communication skills with the parent.Instruments for practical use: Strategies that can be employed in screening for risk factors, in evaluating a family’s need for professional support, and in locating services that are tailored to the family’s specific needs.Glossary: Definitions of terms and concepts, in order to promote a common language and understanding across different disciplines.Case vignettes: Presentation of 20 interactive vignettes that present relevant problems and questions from the perspective of diverse professions . In addition to enabling an understanding of different perspectives and describing potential opportunities and pitfalls, these vignettes are designed to enhance the management and support of children facing a range of types and severities of maltreatment.The goal of the Early Prevention and Intervention in Child Protection e-learning program is to convey theoretical knowledge along with practical strategies on communication and interventions. The topics included in the e-learning program were selected on the basis of several action-research projects in the field of preventive child protection we conducted before e.g. , 25–30) –30 25–30Furthermore, all users registered can communicate directly with each other on the platform.As users work their way through the program, their progress is recorded graphically in a personal profile that displays their current status. Each of the 90 training units takes about 45 min to complete, and is followed by a multiple-choice test. Participants who achieve a minimum average of 70 % on all the tests receive a certificate indicating that they have successfully completed the course. Users can go through the program at the path they want, however, in order to get the certificate users have to finish all 90 units. In addition, those who are eligible for CME credits can claim 86 credit-hours, as approved by the regional medical association. The e-learning program contents a big variety of topics and methods which can be dealt with in every order the user choses. Thus, it is possible to use only parts of the e-learning program and pick the content which the user wants to work through.In a pilot study of the e-learning program that evaluated 45 users , particiThe most valid outcome measure for evaluating the effect of the e-learning training program would be a change in the number of maltreated children in the impacted regions. However, this would require large-scale controlled studies, and would rely on unsupported assumptions about the accuracy of the data on the prevalence of child abuse and neglect in Germany. Accordingly, the program is instead being evaluated by conducting pre-post assessments of participants’ knowledge and understanding of intervention strategies in child protection. The findings will help to answer the following questions: Does participation in the e-learning program enhance professionals’ knowledge in the field? Do participants perceive the program as being helpful and effective? And is the program changing anything about how professionals decide on what interventions to implement, and in their confidence in these decisions?The complete evaluation will be based on data provided by all participants who register for the e-learning program between November 2014 and December 2015. This report presents data from the pre-training questionnaire in order to learn something about the group of users interested in the training, to gather information on specific needs and potential gaps of knowledge and to figure out the need of specific training of observational skills in the field of preventive child protection for all professionals working with infants and toddlers. The final results of the pre-post comparison are expected to be available in March 2017, and will be published in a second paper.Users of the e-learning program were recruited through flyers that were mailed out to a range of professionals and institutions, such as midwife associations, youth centers, child protection agencies, pregnancy and early childhood counseling centers, church- and state-sponsored family counseling centers, nanny services, nursery schools, law firms, and many others. The geographical regions targeted were locations in Germany, Switzerland, and Austria. Respondents are assigned individual subject codes that are associated with their data, so that the information they provide is anonymized and is stored separately from their personal identifying information. The design of the evaluation was reviewed by the ethics committee of the Ulm University Hospital. The evaluation consists of pre- and post-training questionnaires and will answer the following questions:Who is taking part at the training?What are the needs and potential gaps of knowledge of the users?Do they need special training of observational skills?Pre-Questionnaire:Does participation in the e-learning program enhance professionals’ knowledge in the field?Is the program evaluated as being helpful and effective for professionals?Does the program change anything about how professionals decide on what interventions to implement, and in their confidence in these decisions?Pre-post-comparison:Furthermore it will be asked what reasons are keeping some from completing the training. As part of the evaluation, data are collected on participants’ profession and place of residence, in order to determine if all targeted groups and regions are being reached.Theoretical knowledge, assessed through 24 questions to determine the user’s current state of understanding of the course material. Examples include: “What are intuitive parental competencies?”, “What is one of the problems in defining the term “child neglect?”, “How do unrealistic parental expectations affect a child’s development?”, and “What are the consequences to an infant when the parent’s style of interacting is potentially dangerous, e.g., due to borderline personality disorder?”Ability to recognize an infant’s subtle signs of communication, presented in a picture of an infant, lying on his back, with an averted gaze to the right, his hand rolled up to a fist and put to his mouth, while his left hand is holding a stuffed animal. Participants are asked to fulfill observational tasks by assigning the infant’s possible subtle signs of communication to different categories: (a) sign of approach, (b) sign of avoidance, (c) sign of self-regulation, (d) does not apply. The participants are shown a list of subtle signs, which should subsequently be identified in pictures of infants in different situations. Some examples of the portrayed infant’s possible subtle signs of communication include: “Putting hand in mouth/to head/to ear”, “making a fist”, and “averting gaze”.Ability to assess maternal sensitivity, using a case vignette that presents a short description of a family’s situation, including a video clip that shows a mother–child interaction. Based on the information provided, participants must rate the mother’s maternal sensitivity on 4 scales , assess the family’s need for support, and indicate their confidence in this assessment.An overview of the evaluation design is shown in Table The post-questionnaire is presented twice, differing only in the accompanying cover note. Version A automatically appears immediately after fulfillment of the course requirements, and must be completed in order for the participant to apply for the certificate, while Version B is accessed through a link that is emailed 12 months later. In both versions, participants are presented with the same knowledge questions, video clips of infant communication, and case vignette that were provided in the pre-questionnaire, in order to assess the extent of knowledge and skills gained. They are also asked whether they have made any practical use of the course information in their professional duties, and what their overall satisfaction with the course has been. After filling out the questionnaire Version B, participants gain resumed access to course material. Users who within 3 months of registration have not completed any of the multiple-choice tests or who have logged into the program less than twice are sent an email containing a link to a different questionnaire. They are asked to indicate, anonymously, if they have any further interest in the program; if no, what the reasons are for this, and if yes, what has kept them from making more use of it and what circumstances might induce them to do so. The goal is to better understand users’ motivations for completing the program: e.g., acquiring the certificate vs. acquiring knowledge for use in their daily work. Additionally, the responses of different professional groups are compared: for example, physicians and psychotherapists are able to apply their hours of training toward the CME requirements of their professional associations, whereas those in other fields cannot. The ability to acquire CME credits might be a motivation for completing the training. Strategies that might serve as an incentive to other professional groups are being considered and are planned to be implemented.The analysis of the data is being conducted using the statistical program SPSS v. 21.0. Descriptive analyses, Pearson correlations, Bonferroni corrections of error as well as ANOVAs and Scheffé-Tests are being carried out.1294 participants completed the pre-training questionnaire, 92.3 % were female and 7.7 % were male. Mean age was 37.7 years . The majority had a baccalaureate degree, either general (60.4 %) or vocational (26.2 %). About half of the participants had children.The e-learning program was directed at professionals in the fields of child, family, and healthcare services. Respondents were from diverse professional backgrounds, with the highest representations in the areas of social pedagogics (20.3 %), social work (12.3 %), pedagogics (11.6 %), kindergarten teachers (10.4 %) and psychology (10.3 %). Also represented were pediatricians, occupational therapists, pediatric nurses, midwives, child and youth psychotherapists, and family lawyers, at less than 10 % each. The majority of users (87.6 %) were actively working in their profession, with about half of them working full time. The mean number of years of experience in the field was 11.0 years .While 75.3 % of the participants indicated that work with families played an important role, only 26.0 % regarded early preventive intervention as relevant to their profession, only 21.6 % regarded child protection as relevant, and only 14.5 % regarded the field of family counsel as relevant.Of the 24 knowledge questions, the mean number answered correctly was 14.1 . Eleven of the questions were answered correctly by at least 70 % of users; another nine by 40–69 %; and four by fewer than 40 %. On average, the sum of all questions answered correctly was 58.6 %. The frequencies of correctly answered questions of knowledge are presented in Table The number of correctly answered questions varied significantly between the different professionsConcerning the picture that portrayed an infant displaying subtle communication, a mean of 4.92  subtle signs of communication were identified correctly. Seven of the eight signals were correctly identified by at least 56 % of participants  = 3.84, p < .001]: Psychologists answered significantly more questions correctly than kindergarten teachers and  pedagogics and social workers  were answered correctly. Between 10.9 and 37.0 % of participants answered the individual assessments of sensitivity correctly  = 0.98, p = .440).Pearson correlations were used to look for relationships between the number of correct answers given for each of the three measures. A slight correlation was found between scores on the theoretical knowledge questions and the observation of infants’ communication signals, in that the more questions were answered correctly, the more signals were identified correctly. No correlation was found between the ability to correctly assess maternal sensitivity with either of the other two measures. See Table Bonferroni corrections were used to determine the relationship between years of professional experience and the number of correct answers in each knowledge category. According to the three statistical tests conducted, there was a significant correlation between years of experience and the scores on the theoretical knowledge questions: the more experience the people have, the more they know. See Table The internet-based training program “Early Preventive Intervention and Child Protection” was implemented in Germany in response to the need for interdisciplinary training in this field. This paper presents pre-training data from the ongoing evaluation of the program, giving important information on how specialized professionals already are prior to the e-learning training and thus, pointing to the need of specialized training including skills training instead of providing only theoretical knowledge.The e-learning program delivers relevant theoretical information; provides illustrations on topics such as parental mental illness, premature births, and children’s disabilities; employs a range of media methods; provides practical tools, such as ways to assess parent–child interactions and to communicate with parents; and includes systematic screening tools, a glossary of important terms relevant to the area of child protection, and a range of interactive case studies.The pre-training results of 1.294 participants demonstrate a relatively solid state of existing knowledge, with an average of 14.1 correct answers out of 24 (about 60 %) on the theoretical knowledge questions, and an average of 5 correct answers out of 8 on the ability to correctly interpret the subtle language of infant communication. Some differences between the professions were found with physicians showing the highest number of correctly answered knowledge questions and psychologists with the best observational skills regarding the subtle communications signs of infants. Depending on the professions’ knowledge and observational skills, we expect differential benefits from our program. One contributing factor for the relatively good pre-training scores may be that the self-selected participants who chose to enroll in the program are those who have a high interest in further educating themselves in the field of child and family care. However, there are still gaps in knowledge and skills that could be filled by the e-learning program. The ability to assess maternal sensitivity, a crucial indicator for child development [The results found a correlation between scores on the questions of theoretical knowledge and on the ability to assess infants’ communication signals and between years of professional experience and the number of correctly answered knowledge questions. No correlation was seen between either of these scores and the ability to assess maternal sensitivity. This might be explained with the fact, that observational skills cannot be acquired theoretically but need practical training. Thus, our e-learning program includes many video clips, pictures and cases to train these important skills.Any conclusions at this stage are limited, as the evaluation is still in progress and no post-training data are yet available. Apart from this, a methodological limitation of the program evaluation is that a control group is not included. However, a strength is the large sample size, with the N of 1.294. The pre-data of the ongoing evaluation showed, that there is a need to improve providers’ understanding or assessment of maternal sensitivity. By making use of this e-learning training program to better educate themselves in the field of early preventive intervention, professionals working with children and their families should gain confidence in assessing the needs for support. The program described here is aimed at developing these assessment skills as well as improving the confidence needed to apply them. Since 2011, a total of 7.355 users have registered for the e-learning program; 873 have successfully completed it and earned the certificate, and 2.929 are currently enrolled. Once the currently ongoing evaluation is completed, the results should show if this program is indeed enabling professionals to significantly improve their everyday routines in ways that will allow them to help families at risk in a more accurate and suitable manner.


A recent meta-analysis provides evidence supporting the universal application of school-based prevention programs for adolescent depression. The mechanisms underlying such successful interventions, however, are largely unknown. We report on a qualitative analysis of 109 Grade 9 students’ beliefs about what they gained from an evidence-based depression prevention intervention, the Resourceful Adolescent Program (RAP-A). Fifty-four percent of interviewees articulated at least one specific example of program benefit. A thematic analysis of responses revealed two major themes, improved interpersonal relationships and improved self-regulation, both stronger than originally assumed. A more minor theme also emerged—more helpful cognitions. It is postulated that both improved interpersonal relationships and improved self-regulation are likely to enhance one another, and more helpful cognitions may express its contribution through enhanced self-regulation. These findings broaden our understanding of the impact of depression prevention programs, beginning to illuminate how such programs benefit participants.  Depression prevention interventions are particularly appropriate for use with adolescents, with depression considered one of the most common mental health problems of this developmental phase ,2,3. ManThere are both benefits and difficulties associated with applying interventions in a universal or targeted manner. One key advantage of universal approaches is the population health benefits; many people exposed to a low risk  can ultimately generate more clinical cases than a group of fewer individuals exposed to a higher risk . FurtherDespite these positives, universal programs do have their disadvantages. It has been suggested that some universal programs may be unappealing to the public and politicians, and may be unnecessarily expensive . Other pCompared to universal interventions, targeted programs have the advantage of potentially addressing problems earlier, and it has also been argued that it may be most efficient to direct available resources towards high risk groups . HoweverThe most recent meta-analysis exploring the effectiveness of depression prevention interventions in children and adolescents reported positive findings regarding universal programs . SpecifiDespite the evidence supporting prevention interventions, it remains unclear whether program outcomes are attributable to assumed mechanisms of change. Collins and Dozois  reviewedA few studies have attempted to investigate mechanisms of change in depression prevention program for adolescents, although with mixed results. Horowitz and colleagues  comparedPössel and colleagues  evaluateThe program investigated in this study is RAP-A, a resilience program that has been researched systematically since its development in 1997 e.g., ,18,19 anWe report on a qualitative analysis of what participants believe they gained from a universal depression prevention program, RAP-A. We examined the lived experience of program participants by conducting brief individual interviews. We propose that there is value in extending our understanding of universal interventions and that exploring an integrative program such as RAP-A will broaden our knowledge of the underpinnings of efficacious and effective universal programs. We also propose that there is more to be gained from universal interventions than the quantitative data has shown us thus far. SD = 0.40 years). More males were included in the study as a result of different distributions of participant numbers at the single sex schools. Participants in the current study were a sample of Grade 9 students who received the intervention condition in a larger study. The larger study included three intervention schools where students participated in RAP-A as part of the school curriculum, and three comparison schools where students engaged in lessons as usual . Of the 522 students who received the intervention in this larger study, 109 students were selected to participate in the current qualitative study. These participants were selected by a year level coordinator at each school, who was asked to randomly select approximately one-fifth of the students who participated in the RAP intervention. It is noted that this method of participant selection was unlikely to be truly random; but was selected to ensure ease of recruitment for the involved schools. Participants attended one of three Catholic secondary schools  in Western Sydney, Australia. Sixty males and 49 females were included, with an average age 13.98 years  as they were unable to guarantee ten separate meeting times at weekly intervals within one school term. Leaders of each RAP-A group were either health professionals  from local mental health facilities or teachers who had volunteered to participate (44%). An accredited trainer conducted six-hour training of all leaders and supervision and debriefing sessions were routinely held. The schools participating in the larger study requested that the program be delivered over five double periods (Short structured interviews (5 to 10 min duration) were conducted with each participant three months after completion of RAP-A. The interviewer was not previously known to the students, thus reducing the likelihood of students' need to please the interviewer. The taped interviews were transcribed. Responses to the following questions were analysed in this study: “Can you give me specific examples of when you have used skills from the RAP program?” and “Have other people noticed any changes in you?” These questions were selected as they elicited the perceived changes resulting from program participation. The interviewer also asked briefly about what the participants liked most about the program, what they didn’t like and would change, and what they remember RAP-A being about.The transcribed interviews were analysed using thematic analysis, see . This meStudents were able to identify a range of changes they have experienced following participation in RAP-A, with 54% of participants able to nominate at least one specific change they have encountered as a result of their participation. Slightly more girls (61%) than boys (47%) were able to nominate a change. A further 8% stated that the program was beneficial but were unable to nominate specific examples. More boys (13%) than girls (2%) fell into this category. Approximately 25% of participants were either unsure whether they had experienced any changes following their participation in RAP-A or stated that they had not used the skills much or at all. The remainder comprised 7% who stated they had not encountered a situation requiring the use of RAP-A skills and 3% who claimed to possess relevant skills prior to RAP-A participation. Identified changes that were attributed to program participation were analysed further and themes extracted from the data are summarized in A very commonly identified theme was improved relationships with peers and/or family members. This theme captures changes such as an increase in empathy, the acquisition of skills promoting calm and effective discussions, and greater utilisation of social support. Given the wide variety of responses comprising this broad theme, sub-themes were developed.I think about how others feel more—how they’re feeling” and “If someone says something, you just think of what place they’re in and you’re thinking”, “That’s their opinion, so you take that into consideration and respect that”. These responses suggest an improved ability to empathize with others and in the case of the latter response, to use this to modify their own response to another person or situation. Responses highlighting the use of empathy in relation to potential disagreements were also given by a number of respondents, for example, “I just don’t think, “Oh yeah, I feel bad”, but how (is) that other person feeling?” and “(I think)”, “Okay, what are they going through?”...before it used to always be my way”.Many participants reported that they now have greater consideration for others’ feelings, experiences, and perspectives. For example, “A better developed ability to “talk it through” was reported by many students following RAP-A participation. Talking it through refers to the respondent’s ability to effectively and constructively work through a conflict with another individual. Participants gave many examples of being able to talk an issue through with their parents. For example: (I had) a bit of a disagreement (with Mum) and then I remember her (the RAP-A facilitator) telling me that I shouldn’t jump to conclusions and things like that and actually talk it through and that’s what I did. It turned out better than I expected”.“Now we (respondent and parents) just talk. I tell my sister just to talk about it and she’s like “okay”. So now she talks about it”, and “Everyone talks about how they deal with their parents. Like instead of fighting, just talk about it. If the music is too loud or whatever it is. Yeah we actually talked instead of yelling...yeah it was good.” These responses also capture that being able to talk issues through with parents is a very positive experience for adolescents. Other examples include “We had an assignment to do and one of the girls in my group hadn’t done her share and I asked her nicely instead of demanding and now she’s almost finished it”, and “I can remember in an argument with my friends... when we go to the RAP thing, you shouldn’t scream or anything, just calm yourself down a bit and talk through it...It’s not hard or anything and you can use it”. Comments reflecting talking it through with peers were also common and the following examples illustrate the benefits of using assertive rather than passive or aggressive communication to talk an issue through: “This latter response demonstrates an overlap with the following sub-theme, staying calm in a conflict. It also highlights that belief that skills learnt during RAP-A were perceived as personally relevant and easy to use. When we play football, if someone starts swearing, I think, “don’t worry, don’t hit him yet—work things out first”. Before I would have started punching way before”. Other examples that illustrate how the individual was able to stay calm rather than lose their temper include: “My Aunty and Uncle are living with us and we (respondent and her sister) have to share a room...she takes over my room and I didn’t yell at her...I just told her how I felt and said (she) had to clean up the room. Before I think I would have just blown it”.Related to the ability to talk it through is the capacity to stay calm during a potential conflict. Many examples were given of the respondent managing to stay calm rather than behave aggressively when faced with conflict. An example of this that also captures some pertinent inner dialogue is, “Me and a friend of mine, we had a bit of an argument about something...we didn’t argue about it, we just talked it through and got the whole thing fixed up. Before, we would have started yelling and thrown our tempers. I think it’s because of the RAP program. It gave me more confidence to do things I didn’t think I could do before”. “This final example again shows overlap with the previous sub-theme of talking it through.When I need someone to talk to, I just remember who I wrote down”. Other responses made more general reference to the benefits of sharing difficulties with others in order to receive support, rather than keeping things to themselves, for example. “Maybe just talking to people, not feeling so alone...(before) I would have bottled it up and kept it to myself”. Seeking support to achieve specific goals was also reported by some participants, for example, “At school, when I need help I go up to the teacher. I used to just sit there and try to do it myself. It’s been building up my marks because I know how to do it”. The theme of improved interpersonal relations also includes the important capacity to identify and utilize social support. Some respondents referred specifically to a RAP-A activity of identifying possible supports, for example, “The second major theme identified in the data was improved self-regulation; defining self-regulation as a process by which the self modifies its inner states and/or responses in a goal-directed manner . Self-reIt just makes you feel like a better person” and “I used to think of myself, like, I’m nothing, but now instead of having those thoughts I think confidently about myself”. This latter comment demonstrates a particularly powerful change for this individual. Another respondent elucidates how a specific RAP-A activity contributed to an improved self-esteem: “I had really low self-esteem about myself earlier this year...but we did this group thing and we had to write down about other people, what they’re about and stuff and put it in an envelope and I still look at it and stuff. I kind of think what do other people think about me. That’s how my self-esteem boosts. When they write that about me—that I was nice, it really helped me out. I didn’t realize people thought of me that way”. Responses appear to indicate that the strengths-based nature of RAP-A enhanced participants’ views of themselves, as illustrated by the comments, “Finding out more ways to cope with problems and calm down and stuff”. Other examples of an improved ability to keep calm include: “I was pretty stressed one night and I put on some really calm music and relaxed. Before I wouldn’t have done anything” and “That staying calm thing has helped me a lot... I used to go around hitting people if I got angry or bashing in the wall in my room and I used to just yell and yell. Now I listen to music”.An enhanced ability to manage stress and stay calm was noted by a significant proportion of respondents. Respondents reported that participating in RAP-A assisted them to find alternate ways of coping with problems and difficult emotions in order to stay calm, for example: “These two comments capture the important ability to regulate one’s own emotions through engaging in a calming activity . For the sake of clarity, we note that responses specific to interpersonal situations are not included in this sub-theme and are instead captured in the sub-theme, “staying calm in a conflict”. ...like when you’re angry and all that, think about how to calm yourself down”, “It teaches you to sort it out in different ways which is better than just going off...”, and “You just take the time to think. Like if you’re going to get angry you think, “What’s the consequences?””. These responses illustrate an improved ability to exert control over the expression of anger, and in doing so, deal with this difficult emotion in a healthier manner.Better management of anger was another common response, particularly amongst male respondents. Although this theme overlaps somewhat with “keeping calm”, these themes were separated out to recognize their high frequency. A number of participants reported having developed new ways of responding to anger and/or aggressive impulses, for example, “Yeah I think of the positive side of things. I’ve got into trouble or something, I just think of the positive”. Alongside this is the perspective that seeing the positive is beneficial to the individual and is something the participants are trying to do e.g., “I try to think more positive now...”. One respondent explains the change they have noticed about themselves: “I used to be pretty pessimistic about stuff, used to think everything bad is going to happen but now I’ve changed it a bit”. Another respondent gives a pertinent example of trying to identify more helpful cognitions about a situation: “Like not thinking negatively, like if someone stands you up, don’t think they don’t like you, just think they missed the bus or something. Don’t blame them. I was with my girlfriend and she stood me up twice and I just thought it doesn’t matter because she says she likes me and I trust her and I shouldn’t think she doesn’t like me or something and I shouldn’t think negatively”. Although considerably less prevalent than the previous two themes, a third theme was identified in the data—more helpful cognitions. A number of participants gave responses indicating that they have developed the ability to “find the positive” in potentially difficult situations. For example, “This study used qualitative methodology to explore a range of perceived benefits of adolescents’ participation in RAP-A, an evidence-based depression prevention program. Over one-half (54%) of interviewed adolescents could articulate specific examples of program benefit in their daily lives. The two major themes that arose in analysis of the data were improved interpersonal relationships and improved self-regulation, in addition to one minor theme—more helpful cognitions. Nested within the theme of improved interpersonal relationships were the sub-themes improved empathy, “talking it through”, staying calm during a conflict, and increased use of social support. Sub-themes included within improved self-regulation were improved self-esteem, keeping calm, and managing anger. It seems important to reflect upon the potential relations between the themes and sub-themes. During analysis a degree of overlap was noted amongst a number of the sub-themes and across the broader themes. This was deemed unsurprising considering a strong reciprocal relationship appears to exist between the two major themes. Indeed, the evidence to date suggests that interpersonal relationships impact upon an individual’s ability to successfully self-regulate ,27, and The two major themes that were identified are particularly interesting in light of assumed mechanisms of change in such universal programs. Many programs include CBT components, as does RAP-A. However, RAP-A also includes components drawn from interpersonal approaches and interestingly, one of the major themes uncovered in this study echoes this. Although there was a minor theme reflecting cognitive changes, a much greater proportion of responses were about relationships with others and an ability to better manage these. This was somewhat surprising given the program included a strong CBT component. Interpersonal difficulties play a significant role in depressive disorders e.g., ,31 and tFuture research of universal prevention programs may benefit from exploring changes in self-regulation and improved relationships with others, in addition to typically evaluated outcomes such as depressive symptoms. In broadening the range of outcomes we assess, it is necessary to consider the measures that may best measure the impact of these interventions. It may prove difficult to find appropriate psychometric measures to tap into the range of program benefits as currently used measured may be unsuitable or assess too narrow a range of outcomes. Broadening our measurement of program outcomes will also allow exploration of potential mechanisms of change. Further research exploring potential mediators, such as the themes identified in this study, are likely to advance our understanding of these important interventions. Several limitations are present in the present study. The selection of participants to this qualitative part of the study was unlikely to be truly random as it was carried out by year level coordinators at each school, and is likely to have been influenced by matters of convenience. With regard to the conduct of the interviews, a lack of asking probing questions following responses that were short, unclear, or lacking in detail may have contributed to the considerable percentage of participants (46%) who were unable to articulate a specific benefit of the program. For example, students who indicated that RAP-A was beneficial but did not refer to a particular benefit may have been able to give more detailed responses with further probing. Another limitation is the lack of data triangulation; it would also have been valuable to obtain convergent information from significant others such as parents, teachers and peers. It is also important to consider whether participants’ responses were influenced by a desire to please the interviewer with “correct” answers. Indeed, it is plausible that the extracted themes reflect the content of RAP-A, which might be expected given the underpinnings of the program. However, the interviewer was unknown to the participants and reassurance was given that both positive and negative feedback would be useful. In conclusion, students appear to acquire a range of skills from universal depression prevention programs and make use of them in different situations. As such, we do a disservice to adolescents if we restrict our interest in program outcomes to a reduction in depressive symptoms. In the current study improved interpersonal relationships and improved self-regulation appear to encompass the most significant perceived program benefits in adolescents’ daily lives, and it is suggested that these variables have a reciprocal relationship. It seems important to continue exploring such potential mechanisms of change of depression prevention programs in order to inform best practice interventions.


This manuscript describes the development and the preliminary evaluation of a fidelity instrument for the Program for Encouraging Active and Rewarding Lives (PEARLS), an evidence-based depression care management (DCM) program. The objective of the study was to find an effective, practical, multidimensional approach to measure fidelity of PEARLS programs to the original, research-driven PEARLS protocol in order to inform program implementation at various settings nationwide.n = 56) in six states. Known-groups method was used to compare findings from PEARLS programs, other DCM programs, and non-DCM programs. We asked supervisors of the counselors to complete the fidelity instrument on behalf of their counselors to affirm the validity of the results. We examined the association of PEARLS program fidelity with individual client outcomes.We conducted key informant interviews with PEARLS stakeholders, and held focus groups with former PEARLS clients, to identify core program components. These components were then ranked using a Q-sort process, and incorporated into a brief instrument. We tested the instrument at two time points with PEARLS counselors, other DCM program counselors, and non-DCM program counselors (Program for Encouraging Active and Rewarding Lives providers reported the highest fidelity scores compared to DCM program providers and non-DCM program providers. The sample size was too small to yield significant results on the comparison between counselor experience and fidelity. Scores varied between PEARLS counselors and their supervisors. PEARLS program fidelity was not significantly correlated with client outcomes, suggesting that other implementation factors may have influenced the outcomes and/or that the instrument needs refinement.Our findings suggest that providers may be able to use the instrument to assess PEARLS program fidelity in various settings across the country. However, more rigorous research is needed to evaluate instrument effectiveness. The Program to Encourage Active and Rewarding Lives (PEARLS) was developed in the late 1990s by the University of Washington Health Promotion Research Center, in collaboration with our local Area Agency on Aging and a network of senior centers. PEARLS is a depression care management (DCM) program using the Chronic Care model (p = 0.001) and emotional well-being (p = 0.048). Thirty-four percent of individuals in usual care reported any hospitalization during the first 6 months of treatment compared to only 22% of PEARLS clients, suggesting potential health care cost savings , the PEARLS program was shown to significantly improve depression treatment outcomes for frail, socially isolated elders with minor depression and dysthymia when compared to the typical care that these clients received . Fifty-fg p = 0.08. Thirty savings  demonstrCurrently, PEARLS is offered to older adults and adults with epilepsy in approximately 45 sites across 14 states. As it is disseminated nationally, and implemented in various community settings, fidelity becomes increasingly important. Implementation, as it is described in the RE-AIM framework, “refers to the extent to which a program is delivered as intended” both at the site-level and individual level . FidelitThe study was completed in three phases. The first phase involved developing a brief, multidimensional instrument for measuring PEARLS fidelity across sites. The second phase involved conducting a preliminary evaluation of that fidelity instrument. The third phase evaluated the association of PEARLS program fidelity instrument scores with individual client outcomes. This study was approved by the University of Washington Institutional Review Board.We used purposive convenience sampling to identify study participants with experience in PEARLS program development, training, delivery, and receipt. First, we recruited interview participants. The participants included program developers and researchers, program administrators, and PEARLS counselors. Using qualitative methods, we conducted 30–60 min interviews  with these individuals to identify the core, programmatic components of PEARLS from their perspective. Next, we recruited former PEARLS clients who had completed the program within the previous 12 months, and held focus groups with these individuals to identify the core, programmatic components of PEARLS from their perspective. We provided a $25 incentive to focus group participants. Incentives were not provided to interview participants.After the interview and focus group participants identified program components, we used Q-sort ranking  to priorWe used known-groups method data analysis  to condut-tests. We compared the mean scores for PEARLS sites against the mean scores for the other DCM programs and the non-DCM programs. We also compared site-level mean scores by experience level. We compared individual-level scores by education level (up to 4 years of college and master’s degree), by counselor experience , and by PEARLS-specific experience . Instrument validity was assessed using sensitivity and specificity, and we used this information to calculate optimal cut-off scores. We also conducted ROC curve analysis, calculating weighted and unweighted areas under the curve (AUC) as a quantitative method for combining sensitivity and specificity into a single metric. Reliability was evaluated using inter-class coefficients (ICC) between the two survey administration time points.The preliminary analysis involved evaluating mean scores and SDs at the site-level and the individual level using paired For this study, we worked with eight community partners in four states around the U.S.  to examine the relationship between PEARLS program fidelity and PEARLS client outcomes. These PEARLS programs were based on aging, social services, and mental health agencies and represent diverse geographic settings , and racial/ethnic minority communities . Many of these programs serve persons with limited income , with the total possible score ranging from 20 to 100. The interview participants reviewed the anchor points, and provided feedback. We modified the anchor points based on that feedback.Questions are divided into two sections: Program Design and Program Delivery. The Design section includes questions about how the organization implements PEARLS, including training, clinical supervision, client recruitment and referrals, and eligibility criteria. The Delivery section focuses on how the counselor implements PEARLS with their clients, such as the average number of sessions that are delivered at home or that identify and discuss social activities. A copy of the resulting PEARLS Fidelity instrument is provided in Data Sheet 1 in Supplementary Material.We used known-groups method data analysis to compare 12 depression programs in six states: six PEARLS programs, four other DCM programs, and two non-DCM programs. Fifty-two PEARLS counselors and seven clinical supervisors provided responses to both the fidelity instrument and the experience survey: 16 respondents from six PEARLS programs, 23 respondents from four DCM programs , and 20 respondents from two non-DCM programs. One practitioner from a DCM site was excluded, due to missing data. Seventy-three percent of the participants completed the fidelity instrument online. It took an average of 14 min to complete. Participants averaged 48 days between the first and second time point for taking the survey.n = 16). Five counselors attended up to 4 years of college and 10 counselors held Master’s degrees. Six practiced as a counselor for <1 year, five practiced for 1–3 years, and five practiced for over 8 years. No counselors practiced from 4–7 years. Seven counselors implemented PEARLS for <1 year, five implemented PEARLS for 1–3 years, and two implemented PEARLS for over 4 years. The sample size was too small to yield significant results on the comparison between education level, experience as a counselor, and experience with implementing the PEARLS program.The range of scores was 40–89 for the PEARLS counselors (p < 0.05). Average item scores were 3.56 (0.77) for PEARLS sites compared to 2.9 (0.8) for other DCM sites and non-DCM sites. PEARLS sites with more years of experience reported higher scores  than newer programs . PEARLS supervisors (n = 7) from three PEARLS programs completed the fidelity instrument. Mean fidelity scores were comparable between the supervisor and counselor for all three programs [83 (p = 0.87 (NS)]. Individual item scores were similar, with an average difference of 0.04 between items. Unweighted scoring yielded an AUC in ROC analyses of 0.77. Weighting the overall score improved ROC scores yielding an AUC of 0.81. Optimal cut-off scores for weighted PEARLS fidelity score is 77, yielding a sensitivity of 77% and specificity of 67% for identifying PEARLS counselors and non-PEARLS counselors, respectively  70 15.5)] compared to sites delivering other DCM programs [55.2 19.1)] and non-DCM programs [58.0 (13.0)] , which was similar to the average total score of 70  for PEARn = 96) reported speaking a language other than English. Half of those reporting who they lived with stated that they currently lived alone. We did not collect data on education. The mean change in PHQ-9 was 8.79 (5.50). There was little correlation between PEARLS program fidelity and participant outcomes. The correlation between the overall fidelity score and mean change in PHQ-9 was −0.069 (p = 0.444). Several fidelity items were significantly correlated with the mean change in the PHQ-9, but all suggested weak correlations. The most strongly correlated items were those that involved the administration of the PHQ-9 , the use of problem-solving treatment , and the use of homework in between in-person sessions .Program for Encouraging Active and Rewarding Lives participant data were obtained for 127 persons with a mean age of 69 years (8.87). 38.2% identified as White, 26% identified as Hispanic (59% as Mexican), 21.1% as Asian (mainly Filipino with some Vietnames and Korean participants), 11.4% as African-American, and as other races. Only 21% (26 clients) provided data on their income, with all but three of these clients reporting very low income as defined by the Federal Poverty Level, Median Income, or Housing and Urban Development criteria depending on the PEARLS program. Almost half (46.7%) of the respondents that provided information on language spoken at home . Eighty-four PEARLS participants and 16 counselors were included in this revised dataset. The mean change in PHQ-9 was slightly higher than in the original group [9.00 (5.25)]. The mean (SD) total PEARLS fidelity score was also higher [83.42 (5.29)].n = 106, 9.16 (5.42)] and those falling below 70 . The difference was also not significant when the cut point was set at 80 , with a mean PHQ-9 change of 8.94 (5.38) (n = 81) for those at or above the cut point and 8.52 (5.78) (n = 46) for those below the cut point.We dichotomized the full dataset to look at whether falling above or below a cut-off for the PEARLS fidelity total score predicted a difference in the mean change in PHQ-9 score. Using the cut-off of 70 , there was not a significant difference between mean change in PHQ-9 between those falling above or at 70 [We summarized the responses to the fidelity instrument in Table The PEARLS fidelity instrument is a brief, easy-to-use, low-cost option for PEARLS program staff to assess fidelity during program implementation. The tool takes an average of 14 min to complete, allowing for routine assessments by clinical supervisors and counselors. For example, a PEARLS program may use the fidelity instrument periodically as a way to assess whether a counselor is continuing to maintain fidelity to the original program model, and to identify where adaptations have been made. Clinical supervisors may use the instrument to guide ongoing clinical supervision sessions and activities. Funders of PEARLS programs and agency administrators may be interested in the PEARLS fidelity instrument as a quality assurance tool to guide ongoing implementation.It is surprising that fidelity to the PEARLS program and client outcomes are not more strongly correlated. Also, the discrepancy between clinical supervisor and counselor ratings suggests that there is variation in how each party completes the instrument, and perhaps in how clinical supervisors are involved in the program. We know, for instance, from PEARLS technical assistance activities that some clinical supervisors are more intimately involved with regularly providing supervision that helps guide counselors in adhering closely to the PEARLS model, while others are brought in less frequently and advise more on co-occurring chronic conditions and medication use than on the PEARLS model. More rigorous research is needed to confirm the effectiveness of the tool  before it is disseminated widely.Research suggests that translation of evidence-based programs must be completed systematically, both at the site-level and individual level, to assure effectiveness . The RE-It is important to evaluate PEARLS counselors at the site-level to assure that clients are receiving the best possible treatment. It is also imperative to look at the PEARLS program at the site-level to prove to funding agencies that it is effective –14. ThisThe PEARLS mean score on the fidelity instrument was lower than expected (70.5 out of a possible 100), and Table Another example is expanding participant eligibility criteria to better align with the multifaceted, complex clients that agencies see every day. Previous research  suggesteThese findings also point to the fact that fidelity is only a piece of the implementation of PEARLS. The weak, generally non-significant correlations between fidelity score and client outcomes may suggest that other factors are at play, which impact whether a client improves their depressive symptoms. From our work providing technical assistance to PEARLS programs, we know that at the individual level, motivation, stigma about depression, physical health and management of other comorbidities, informal and formal support, and mobility and function are all factors that influence whether someone successfully participates in PEARLS. At the site-level, other approaches for improving EBP implementation include outcome monitoring, regular and structured supervision, effective organization and climate, rigorous selection and retention of team members, and ongoing consultation and technical assistance .After measuring fidelity, it is important to then provide fidelity feedback to EBP providing agencies so that they can modify their services based on feedback from their fidelity reviews . One exaThe fidelity instrument that we developed in this study may be the most effective way to evaluate effective implementation in various locations and community settings across the country. While independent, observational measures of fidelity are ideal, this instrument provides a practical, user-friendly tool that programs can use internally and at minimal cost for monitoring program quality. Further work is necessary to ascertain the validity of the instrument given the discrepancy between counselor and supervisor ratings and it may need refinement to correlate more strongly with client outcomes.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.This paper is included in the Research Topic, “Evidence-Based Programming for Older Adults.” This Research Topic received partial funding from multiple government and private organizations/agencies; however, the views, findings, and conclusions in these articles are those of the authors and do not necessarily represent the official position of these organizations/agencies. All papers published in the Research Topic received peer review from members of the Frontiers in Public Health  panel of Review Editors. Because this Research Topic represents work closely associated with a nationwide evidence-based movement in the US, many of the authors and/or Review Editors may have worked together previously in some fashion. Review Editors were purposively selected based on their expertise with evaluation and/or evidence-based programming for older adults. Review Editors were independent of named authors on any given article published in this volume.http://www.frontiersin.org/Journal/10.3389/fpubh.2014.00200/abstractThe Supplementar Material for this article can be found online at Click here for additional data file.


We found that the cytoplasmic isoform QKI-6 regulates AS of polyguanine (G-run)-containing transcripts in OLs and rescues aberrant AS in the qkv mutant by repressing expression of two canonical splicing factors, heterologous nuclear ribonucleoproteins (hnRNPs) F and H. Moreover, we identified a broad spectrum of in vivo functional hnRNP F/H targets in OLs that contain conserved exons flanked by G-runs, many of which are dysregulated in the qkv mutant. Interestingly, AS targets of the QKI-6-hnRNP F/H pathway in OLs are differentially affected in SWCs, suggesting that additional cell-type-specific factors modulate AS during CNS and PNS myelination. Together, our studies provide the first evidence that cytoplasmic QKI-6 acts upstream of hnRNP F/H, which forms a novel pathway to control AS in myelinating glia.The selective RNA-binding protein quaking I (QKI) plays important roles in controlling alternative splicing (AS). Three QKI isoforms are broadly expressed, which display distinct nuclear-cytoplasmic distribution. However, molecular mechanisms by which QKI isoforms control AS, especially in distinct cell types, still remain elusive. The quakingviable (qk More thin (MAG) .v/qkv mutant  F and H are functionally orthologous splicing factors, both of which target polyguanine (G-run) sequences within or surrounding alternative exons in pre-mRNAs to regulate AS . During v/qkv mutant mice results in aberrant over-production of both hnRNP F and hnRNP H. Such dysregulation of hnRNP F/H in OLs can be completely rescued by transgenic expression of the cytoplasmic QKI-6 alone. Furthermore, we identified a pool of functional hnRNP F/H targets in vivo, which are differentially affected in OLs and SWCs of the qkv/qkv mutant mice. These findings reveal that cytoplasmic QKI-6 and hnRNP F/H form a novel regulatory pathway to control AS in myelinating glia.We report that the cytoplasmic QKI-6 acts upstream of hnRNP F/H to regulate AS in myelinating glia. Deficiency of QKI in OLs and SWCs of the qkv mouse colony was originally purchased from Jackson Laboratory and maintained on campus. The wt/qkv, qkv/qkv and PLP-FLAG-QKI-6 transgenic mice were generated and identified by PCR-genotyping  was performed using DyNaMo Sybr Green qPCR kit (Thermo-Scientific), and quantified by ΔΔCt. Primers are listed in Supplementary Table S2, or were previously published (RNA was isolated by Trizol extraction (Invitrogen). Samples were DNase treated with the Quantitect kit (Qiagen) prior to reverse transcription (RT) using random hexamer primers (Promega) and SSII reverse transcriptase (Invitrogen), or using the Quantitect kit. Semi-quantitative RT-PCR was performed using primers that detect the alternative splice variants simultaneously. After electrophoresis, the RT-PCR products of AS isoforms were quantified with ImageJ. The intensity of ethidium bromide staining of the PCR products that contain either exon included or skipped was quantified. The % inclusion of the alternatively spliced exon in each sample was calculated. Results in qkublished ,28,32–33Brain stems derived from mice expressing the FLAG-QKI-6 transgene specifically in OLs were dissected, minced and immediately UV cross-linked at 400 mJ in a Stratalinker 1800 (Agilent Technologies). In addition, HOG cells transfected with FLAG-QKI-6 or pcDNA control, together with reporter constructs, were also subjected to UV cross-link under the same conditions. Cells or homogenized tissues were lysed on ice in a buffer containing 20 mM Tris pH 7.5, 100 mM KCl, 5 mM MgCl2, 0.5% Triton X, a cocktail of protease inhibitors including pepstatin, leupeptin, aprotinin, phenylmethanesulfonyl fluoride and RNase inhibitor. Lysates were centrifuged at 800 × g for 5 min at 4°C to remove nuclei. SDS was added to supernatants to a final concentration of 0.01% or 0.5% as indicated in the corresponding figure legends and centrifuged at 16 000 × g for 15 min at 4°C. Four percent of total supernatant was kept for detecting RNA and protein inputs, respectively. Samples were pre-cleared for 30 min at 4°C with sepharose 4B beads (Sigma) that were pre-balanced in the IP buffer. Twenty microliters of pre-balanced anti-Flag-M2 beads (Sigma) were added to the supernatants and incubated overnight at 4°C. Centrifugation was performed at 100 × g at 4°C to isolate the immunoprecipitated complexes on the beads, which were washed three times in a buffer containing 20 mM Tris pH 7.5, 100 mM KCl, 5 mM MgCl2, protease inhibitors and 1% Triton X. The beads were then resuspended in a buffer containing 5 mM Tris pH 7.5, 0.32 M sucrose and 2% SDS. Seventy-five percent of the immunoprecipitates on beads were taken out and treated with proteinase K for 20 min. After centrifugation at 8000 × g, the RNA was isolated from the supernatant by phenol/chloroform extraction, and subjected to RT-PCR to detect FLAG-QKI-6 associated RNA. For experiments using reporter plasmids, samples were DNase treated before RT, with an independent replicate that was not reverse transcribed, to assess complete removal of plasmid DNA contamination. The remaining 25% of the immunoprecipitates were incubated at 65°C for 3 min in 1× Laemlli buffer, centrifuged, and the supernatant was subjected to SDS-PAGE and immunoblot.P-value < 0.05 was considered statistically significant and is indicated by *.Statistical analyses were performed using Student's t-tests to compare two sample sets, one-way ANOVA and Tukey's post-test when comparing three or more sample sets, or two-way ANOVA and Bonferroni's post-test when comparing three or more sets of paired conditions. Standard errors are depicted in all bar graphs. in vivo, we performed UV-crosslinking immunoprecipitation (CLIP) to isolate mRNA complexes formed with cytoplasmic QKI-6 from the brain of transgenic mice that express FLAG-QKI-6 specifically in OLs . Consistent with the known function of QKI-6 in suppressing translation of its bound mRNAs . Quantification of exon inclusion/exclusion is shown in Figure v/qkv OPNs repressed exon inclusion of ENY2 , UDP-acetylglucosamine pyrophosphorylase 1 (UAP1), ataxin-2 (ATXN2), and Z-band alternatively spliced PDZ-motif containing protein (ZASP)  Figure . Hence, ) Figure ,25,39–40Not all the reported hnRNP F/H targets are dysregulated by QKI deficiency, represented by the muscle blind-like protein 1 (MBNL1) Figure . Consistv mutation also causes QKI deficiency in SWCs that myelinate the PNS (v/qkv SCN (Figure v/qkv SCNs, recapitulating what was found in qkv/qkv OPNs. Elevated expression of hnRNP A1, a known target of QKI-6 in OLs (v/qkv SCNs (Figure v/qkv OPNs, the MPZL1 pre-mRNA also displayed dysregulated AS in the qkv/qkv SCNs (Figure v/qkv OPNs (Figure v/qkv SCNs (Figure The qk the PNS . QKI-6 iN Figure , which iN Figure . Both hn6 in OLs , was alss Figure . Thus, ts Figure . Howeverin vivo functional targets of the QKI-6-hnRNP F/H pathway, which play diverse roles in glia function and myelin development, some of which are also implicated in neurological diseases.Our studies discovered that QKI acts upstream of two canonical splicing factors hnRNP F/H, which forms a novel post-transcriptional pathway to regulate AS in myelinating glia of the CNS and PNS. We found that in contrast to nuclear QKI-5 that directly regulates AS in muscle cells , cytoplahnRNP F and hnRNP H are functional orthologues expressed in many cell types and control AS of numerous G-run containing pre-mRNAs ,24–25. Cv/qkv OLs, although all QKI isoforms are reduced, deficiency of QKI-6 quantitatively exceeds the other isoforms (v/qkv OLs during myelin development, together with the correction of aberrant hnRNP F/H over-expression by the OL-specific FLAG-QKI-6 transgene, clearly demonstrates the essential role of QKI-6 in regulating hnRNP F/H and their downstream AS targets in CNS myelination. Importantly, the FLAG-QKI-6 transgene neither rescued the deficiency of QKI-5 (Regulation of hnRNP F/H expression by cytoplasmic QKI-6 provides one example for modulating hnRNP F/H-dependent AS in a cell type-specific manner. Expression of the qkI gene is detected in nearly all cell types except brain neurons . Nuclearisoforms . The impof QKI-5  nor incrof QKI-5 . Hence, of QKI-5 ,22,42, tin vivo (v/qkv OLs leads to over-expression of hnRNP F/H proteins without affecting the levels of their mRNAs. However, we were unable to detect association of QKI-6 with the hnRNP F mRNA in OLs even under non-denaturing conditions. This could possibly be caused by unknown RNA-binding proteins that mask the QRE in hnRNP F mRNA, which either renders the hnRNP F mRNA inaccessible by QKI-6 or permits only labile interactions with QKI-6 in OLs. Considering the emerging evidence that QKI regulates expression of selected microRNAs (Although QKI isoforms can form heterodimers and shuttle between the nucleus and the cytoplasm , both thin vivo ,14,16,23in vivo , QKI deficroRNAs ,43, whetv/qkv mutant (in vivo in the same direction as that by hnRNP F/H. However, besides coordination with hnRNP H (All the AS targets of the QKI-6-hnRNP F/H pathway we identified in this study encode protein isoforms that play distinct functions, often reciprocally regulated during myelin development. MAG and PLP are two examples of such regulation, which are also severely dysregulated in the qkv mutant . AS of Mv mutant ,44. AS ov mutant ,45. It iv mutant ,46, whic hnRNP H , hnRNPA1 hnRNP H . The hnREmerging evidence suggests dysregulation of AS in human disorders that involve deficiency of QKI, such as schizophrenia and glioma ,49. ReduSupplementary Data are available at NAR Online.


This paper aims at presenting programs targeted at the prevention of adolescent depression applied with Spanish-speaking populations that have been developed in Spanish-speaking countries and are mostly published in Spanish. These programs have been developed under different cultural contexts in Spain and Latin-America. The main goal of this paper is to make the studies and movements of the Spanish-speaking literature in this field accessible to the non-Spanish-speaking part of the research community. Therefore, after an introduction referring to possible cultural differences regarding depression in general and epidemiological basics, several programs are introduced. In total 11 programs will be shortly presented and discussed. After revising the programs it can be concluded that in the Spanish-speaking world many programs have been developed and conducted following current state of the art-approaches for adolescent depression prevention. Further research is needed especially targeting possible cultural and contextual aspects of prevention measures and their efficacy and efficiency. Depression is a major public health problem worldwide, as it shows high prevalence and leads to disability and individual suffering . As deprAll this is also true for the hispanophone sphere: more than 500 million individuals in the world speak Spanish, therefore it is the second language in the world by number of speakers and the second language for international communication . Twenty This article aims at presenting prevention programs targeting adolescent depression that are applied to Spanish-speaking populations that have been developed in Spanish-speaking countries and are mostly published in Spanish. There is a conceptual focus on cognitive-behavioral prevention techniques. Making the programs available to a broader public seems worthwhile as it fosters cross-cultural exchange in the area of public health, and might inspire new clinical and research strategies. However, this article might not represent all research projects in this field conducted in the hispanophone world. There are several reasons for this: one main reason is the fact that there is no Spanish research database that includes all journal articles as well as master and doctoral theses, and other kind of scientific publications. Furthermore, the reality within the Spanish-speaking research community is not equivalent to the English-speaking publication culture. Many research projects are not published in international journals but in books and local journals not covered by the common databases. The attempt was made to broaden our search strategy by contacting experts; however, pretending to have covered the wide range of research activities in the field of the many Spanish-speaking countries might be presumptuous. Nevertheless, the research presented in this article might still serve the purpose to at least present a significant part of the Spanish-speaking literature.The article is structured as follows: first, some short remarks regarding prevalence of depression and discussion regarding cross-cultural aspects of depression will be given. After introducing our search strategy, we will first present programs applied to Spanish-speaking populations that have been evaluated. Then, we will present programs that are currently work in progress, and finish with a discussion of the presented results.The prevalence of depression among Spanish-speaking adolescents is comparable to what is reported in the rest of world. Namely, prevalence rates reported in adolescent populations range from 10.3% in Spain  and 17.0et al. [i.e., vocabulary is clear and understandable), person , metaphors (symbols and concepts), content , concepts (treatment concepts concordant with culture and context), goals , methods , and context  [The treatment of child and adolescent depression has also been covered widely in the hispanophone literature. A meta-analysis on the effects of psychotherapy on child and adolescent depression published in Spanish including fifteen controlled trials carried out between 1980 and 2002 revealed effect sizes of d = 0.53 for after the treatment and an effect size of d = 50 follow-up . Howeveret al.  supportset al. . The pro issues) . Further issues) . The mod issues)  to a Pue issues) ,11,12. AIn summary, even if there are considerable cultural and societal differences regarding the conceptualization of depressive mood, the phenomenon of depression in general and adolescents’ depression in particular seem to be comparable across cultures. Adolescent depression is a common problem as relevant in the hispanophone populations as in the rest of the world. Therefore, evaluating and implementing prevention programs suitable for different Spanish-speaking populations is an important task from a general public health perspective.. They highlight that a remarkable number of programs have been developed and evaluated to prevent children and teenager depression with promising results. However, all the revised programs took place in developed countries in English. The authors underline the importance of increasing research in this area in the reality of Spanish-speaking developing countries in Latin-America. Accordingly, they discuss the difference between efficiency of very expensive controlled trials and the lack of effectiveness in terms of possible implementations in the Latin-American reality. They supported the inclusion of psychosocial factors like poverty, ethnicities, rural vs. urban populations, cultural differences, e.g., regarding gender roles. Furthermore, they suggest fostering less costly dissemination of prevention programs, e.g., by training of non-psychologists like teachers as facilitators of prevention programs. Moreover, Martinez, Rojas and Fritsch [The interest in prevention of adolescent depression is also significant in the Spanish-speaking literature. This is reflected in several literature reviews and reflections on that topic that have been published. For example, a study with Argentine adolescents focused on anxiety and depression symptoms; the aim was to develop a profile of prevention measures needed on the basis of adolescents’ needs as assessed in surveys and group sessions similar to focus groups . Further Fritsch  conducteThe search for published studies on prevention programs for adolescent depression was performed in steps: first, the data bases Psicodoc, Dialnet Redalyc and LILACS, including the most important Spanish journals were researched with the key words “adolescents”, “prevention”, “depression”, and “cognitive-behavioral therapy” . Original articles were considered if they included prevention programs with depression prevention as a primary goal; programs with further goals than depression prevention were also included. However, only reviews in Spanish mostly covering English literature resulted from this search but no original study. As a second step, Spanish language meta-analyses, studies on risk factors, and review papers on prevention of depression in the adolescent population were reviewed. Thirdly, the index of important journals in the field as reflected in the review articles  were analyzed separately. Furthermore, the experts appearing in the literature were additionally contacted by e-mail and asked to send information about their own research and colleagues researching in the field. By doing so, we also identified a number of programs that are being researched in ongoing research projects, but only preliminary results are available in congress publications as sent to us by the authors.In the end, these research strategies yielded five Spanish-speaking prevention programs, which have been studied in randomized controlled trials and conducted, and published in Spanish, and a sixth one, that has been published in English. Furthermore, five ongoing trials were detected with preliminary results that also seemed worthwhile reporting.The following sections aim at presenting prevention programs that have been conducted in Spanish by Spanish-speaking research teams in Spanish-speaking countries. All studies presented in this section have a non-treated, randomized control group and published result data. In contrast, in the last part of the section, a couple of ongoing studies will be shortly presented that do or do not have a control group or results have not yet been reported. All presented studies are summarized in This program aims at improving self-esteem and preventing depressed and anxious states in adolescents between 11 and 14 years of age and was developed and implemented in Valencia, Spain . The proIn 1996, a study was published by Mestre and Frias  implemenThe depression score of the CDI did show an improvement after the program; however, the control group did improve as well, so that there was no significant observable effect of the program. Nevertheless, self-esteem improved significantly in the treated group in comparison with the non-treated control group. Moreover, a significant interaction between age and treatment condition was observed: students older than 12 years  benefited more from the program than the younger ones. No sex differences in terms of program effects could be observed. Unfortunately, none of the analyses took into account the nested data structure of each individual belonging to a school group. The authors conclude that the program had the planned positive effects on proximal variables—here self-esteem—particularly in adolescents aged 12 years and older. They argue that adolescents in this age are more prone to affective symptoms and thus suggest the age of 12 and above as ideal for the application of prevention programs.Olmedo, Del Barrio, and Santed  developeThe authors underline the advantage of implementing the program at schools, as the school setting represents a reference point where adolescents form their self-images being exposed to performance related, and competitive situations as well as affiliative processes. They also pointed out the fact that the school setting is the place where academic as well as social status is determined and thus typical risk factors for depression begin .vs. control group is unfortunately not mentioned). The intervention took place in public schools in Córdoba, Spain. The participants were group by group randomized to the prevention or to a non-treated control group. All students answered questionnaires before, as well as one week and five months after the intervention.Two studies have been published so far, empirically testing the program: In the first study  225 adolThe two groups did not differ at any baseline rating. At baseline, the authors conducted several hierarchical regression analyses, showing the expected associations between the protective factors self-esteem, social skills, and interpersonal problem solving, and depressive symptoms as well as the anxiety measure. They interpreted this as empirical support for the chosen content of the prevention program. T-tests conducted comparing the post scores between treatment and control group show significant differences as expected, while the protective factors showed increased scores, compared to the control group. Furthermore, hierarchical regressions performed with change scores (pre-post) confirm, that the change in self-esteem and problem solving skills predicts the change of the amount of depressive symptoms after the prevention program.Regarding the methods presented in the article, there are some caveats: first, as the treatment was conducted group by group the statistical analysis should take the nested data structure into consideration, which was not the case in this study. Secondly, the treatment effects in the comparison between treatment and control group were assessed without controlling for base line scores. Thirdly, no effect sizes are reported. However, the big sample, consistent results and the analysis including protective factors as mediating the effect on depression underline the validity of the study results.A second study  was execA further group-based cognitive-behavioral prevention program has been developed by Gómez and colleagues in Colombia . It is bN = 147 adolescents in Medellín, Colombia aged between 12 and 16 years old, who were in seventh grade. The classrooms were randomly assigned to the experimental and the control groups. Short (directly after finishing the program) and middle term (six months after) changes in following variables were measured: depressive symptoms positive and negative automatic thoughts, positive and negative emotions and suppression of thoughts base-line. Results indicated higher symptom levels in female than in male adolescents, as reflected in heightened level of depressive symptoms, negative automatic thoughts, negative affect and thought suppression. Students’ depressive symptoms were reduced from the baseline to the post assessment of depressive symptoms. The differences between control and treatment group were only marginally significant demonstrating reduced depressive symptoms for the experimental group [A study was conducted with a sample of al group . In sum,In a further study, the program was reformulated and only the cognitive part was applied as a singly module named Educación en la cadena pensamiento-emoción-conducta  . Again, n = 107) formed the experimental group and 43.68% (n = 83) the control group. In the experimental group 44.85% (n = 48) were female and 40.93% (n = 34) in the control group. The program was applied in six weekly sessions of 45 min each run by trained psychologists; school teachers were not present. As the program was mainly targeted at cognitive processes the main outcome variable was the Automatic Thoughts Questionnaire.This program was evaluated with 190 students aged between 14 and 17 years in public schools, whose classrooms were randomly assigned to an experimental or a control group. 53.31% (p = 0.018) [Results indicated that actually negative automatic thoughts show a significant decrease after the program as compared to the control group and controlled for baseline  . No chanCova, Rincón and Melipillán  developeN = 108) and the universal application to complete classes . The program did not show significant effects on depressive symptoms, anxiety, self-harming or externalizing behaviors in any of the two modalities as compared to a non-treated control group. While focusing only on the constructive cognitive reflection was there a significant positive effect compared to the control group. Moreover, as in other studies in the indicated modality participants reported more satisfaction than in the universal condition. However, one quarter of the female teenagers participating in the targeted program reported being irritated by the fact that they participated in the program, a reaction that was reported in no more than 6% of the universal conditions. In sum, the authors conclude that dose and scope of prevention programs were not adequate for the target population.The program was implemented in two modalities: the indicated form was applied to teenage girls with sub-threshold depressive symptoms   based onThe innovative aspect of the EMAS program is that is has been integrated into the regular school curriculum and school teachers are trained to implement it. Also the format of the program was developmentally and culturally adapted to Puerto Rican adolescents. The ongoing study consists in evaluating the efficacy of the program in three schools in Puerto Rico using a classroom by classroom randomized study with pre/post measures and four follow ups. However, results have not been available yet. Nonetheless, a pilot study indicated that the program can be effectively delivered by teachers and was well accepted by students .Smile is a program developed by Sánchez and Méndez in Spain  based onThe program is organized in four modules: (1) development of curiosity and motivation to engage in the program; (2) Emotional education; (3) Behavior therapy ; interpersonal skills) and (4) optimism.The novelty of the program is the emphasis on motivation and curiosity in order to encourage participation in the program, and the inclusion of elements of positive psychology. A preliminary study focusing on the increase of motivation and interest of adolescents to participate in programs for the prevention of depression was conducted. The results are promising regarding the usefulness of the pre-intervention. Furthermore, they found a negative correlation between curiosity about change and anxiety, and a positive correlation with optimism .The program was created by Méndez, Espada, Orgilés at the University of Murcia, Spain . The maiReferring to findings regarding the psychological vulnerability and healthy behavior of Argentinean adolescents ,36 CingoThis compilation of hispanophone literature on adolescent depression prevention shows that there are relevant contributions to field of prevention research that might hardly be acknowledged in the international research community. The studies refer to similar theoretical backgrounds and psychotherapy techniques as in the Anglo-Saxon literature. For example, the majority of the programs are based in cognitive-behavioral aspects of depression, showing that teaching certain behaviors and abilities lowers the risk factors and makes it less likely for an adolescent to develop depression  Furthermexico City: The migrant status and the cultural context differ and lead to different needs for cultural adaption. Additionally, metaphors and content needs to be changed often: e.g., social norms are culturally sensitive. What is seen as adequately assertive in the USA might be rude in Colombia. Therefore, behavioral intervention, e.g., targeting social skills need to be adapted, as it was done in most of the mentioned programs. Also values are culturally different, so life goals and thus even goals in prevention and therapy might be different. Interestingly enough, these adaptations are seldom mentioned in publications, which might be a bias: the more similarity to already evaluated programs is suggested, the easier it is published.Following the structure of cultural adaptation as introduced by Bernal and colleagues , there aMany programs focus one the training of emotion regulation skills. This goes in line with recent “third wave” therapies that have been published. In terms of cultural differences, emotion regulation is a topic of particular interest. For example, the expression of emotions is a fundamental aspect of emotion regulation which is known to vary across cultures; it is assumed that there are different display rules of emotional expression depending on the cultural context , beside To sum up: many cultural aspects are expected to be highly relevant in depression prevention. However, beside private conversations this is hardly reflected in the sparse literature on non-English prevention trials. Following this further, the majority of the literature found in prevention focuses on the principal risk factors for depression and in the development of interventions, however clinical trials proving the efficacy of the programs in Latin American adolescents are often not published for an international audience. Another problem is that sometimes trials lack strong study designs, or programs focus on other life skills and the central variable is not depression, instead they include variables such as alcohol or psychoactive substances abuse ,41. Manyi.e., the extent to which the programs achieve their intended effects in the usual clinical setting is far from being tested satisfactorily. Still, this review might show that important first steps are done in Spanish-speaking countries to overcome this gap.To conclude, it is commonly agreed upon that there is a need for more evaluations of the running programs and a dissemination of the findings in international publications. However, the scientific literature on the topic and the presented programs reflect a deep integration in international mainstream and is in state of the art in terms of conceptual foundations, development, and dissemination of prevention programs for adolescents. In general, however, beside scientifically proven efficacy of the programs, efficiency,