Halophiles are extremophilic microorganisms growing optimally at high salt concentrations. There are two strategies used by halophiles to maintain proper osmotic pressure in their cytoplasm: accumulation of molar concentrations of potassium and chloride with extensive adaptation of the intracellular macromolecules  or biosynthesis and/or accumulation of organic osmotic solutes ("osmolyte" strategy). Our work was aimed at contributing to the understanding of the shared molecular mechanisms of protein haloadaptation through a detailed and systematic comparison of a sample of several three-dimensional structures of halophilic and non-halophilic proteins. Structural differences observed between the "salt-in" and the mesophilic homologous proteins were contrasted to those observed between the "osmolyte" and mesophilic pairs.The results suggest that haloadaptation strategy in the presence of molar salt concentration, but not of osmolytes, necessitates a weakening of the hydrophobic interactions, in particular at the level of conserved hydrophobic contacts. Weakening of these interactions counterbalances their strengthening by the presence of salts in solution and may help the structure preventing aggregation and/or loss of function in hypersaline environments.Considering the significant increase of biotechnology applications of halophiles, the understanding of halophilicity can provide the theoretical basis for the engineering of proteins of great interest because stable at concentrations of salts that cause the denaturation or aggregation of the majority of macromolecules. Organisms thriving in "extreme environments", such as thermophiles, alkalophiles, acidophiles, halophiles, piezophiles and psychrophiles, have drawn much interest in the scientific community because of the molecular adaptation they underwent during evolution and for their biotechnological potential -4. The eHalophilic microorganisms are salt-loving extremophilic organisms that grow optimally at high salt concentrations. They were found  mainly iArchaea kingdoms. Eukaryotic halophilic microorganisms, such as fungi and algae, are also known [Distribution of halophilic microorganisms within the tree of life shows that they are widespread in the bacterial and so known .Archaea. The other strategy of haloadaptation is based on the biosynthesis and/or accumulation of organic osmotic solutes (osmolytes) such as ectoin, glycine betaine or others [All halophilic microorganisms share a basic property: their cytoplasm must be at least isoosmotic with their surrounding medium. There are two strategies used by halophilic microorganisms to maintain proper osmotic pressure in their cytoplasm. The first involves accumulation of molar concentrations of potassium and chloride. This strategy requires extensive adaptation of the intracellular enzymatic machinery to the presence of salts, as the proteins should maintain their proper conformation and activity at near-saturating salt concentrations. The proteome of such organisms is highly acidic, and most proteins denature when suspended in low salt. Generally, the microorganisms relying on such "salt-in" strategy are obligate halophilic r others . Cells rr others .Halophilic proteins from "salt-in" organisms are distinguished from their non-halophilic homologous proteins by exhibiting remarkable instability in low salt concentration and by maintaining soluble and active conformations in an environment generally detrimental to other proteins. Indeed, hypersaline conditions favor protein aggregation and collapse, interfere with the electrostatic interactions between protein residues, and are responsible for a general decrease in the availability of water molecules . HalophiArchaea that adopt the "salt-in" strategy (SALTIN), and 7 from Eubacteria that adopt the "osmolytes" strategy (OSMOL). In this paper, the entire analysis was carried out considering the two groups separately.A set of 15 halophilic enzymes, 9 of which from "extreme" halophiles and 6 from "halotolerant" organisms, was collected along with their non-halophilic structural homologues  have a quaternary structure different from their non-halophilic homologs (Table 552 from Marinobacter hydrocarbonoclasticus (PDB ID: 1CNO) and from Pseudomonas stutzeri (PDB ID: 1ETP) has been included in the analysis, for the reasons explained in Methods section.Four pairs of halophilic enzymes  and the magnitude of the relative polar and apolar components, protein structures were used in their quaternary form. The surface polar area formed by oxygen and nitrogen atoms was calculated. The area subset formed only by side-chain oxygen or nitrogen atoms  was also considered.ΔApA in Table In SALTIN enzymes, the fractional apolar component of the relative solvent accessible surface is significantly smaller than the corresponding area in non-halophilic counterparts  between residues was calculated for three different structural regions namely the core, the interface between the monomers and the protein surface. Residues were assigned to the various structural regions according to the alternative accessibility thresholds described in the Methods section.ACA in the core of SALTIN halophilic proteins is not significantly different, according to the statistical tests, from the ACA of their homologous counterparts. However, it is consistently smaller Figure . This trΔACAs were negative except for the pair 3IFV-1RWZ. The analysis at interface for OSMOL enzymes is reduced to two pairs and is therefore of no statistical interest, however, the ACA formed by interfacial residues in halophiles is comparable to that of non-halophilic organisms.Likewise, ACA in the SALTIN monomer interface is not significantly dissimilar from the ACA of their non-halophilic counterparts. However, even in this case, all the The surface ACA in SALTIN and OSMOL halophilic enzymes is not significantly different from the corresponding surface in the non-halophilic counterparts Figure .ΔΔApAU-F) between each halophilic and non-halophilic pair, have been calculated. According to the Wilcoxon and the t-test, none of the average values were significantly different from 0. Distribution of the differences in the SALTIN and OSMOL samples are reported in additional file Differences in apolar area buried upon folding  were calculated. The conserved contacts between hydrophobic residues (CHC) were identified for each pair of structures, and were selected only those formed by evolutionary conserved residues. Then for each CHC, the apolar contact area formed by the pair of residues was calculated. The number of CHCs selected varies for each enzymatic family depending on the relative degree of conservation of residues in that family Table .In SALTIN sample the average ACA in CHCs is significantly smaller in halophilic enzymes than non-halophilic counterparts Table . At vari→ halophile with a Z-score equal to 4.34. At variance, the most frequent exchange in the OSMOL CHCs is Leu → Ile with Z-score 3.74.Statistics on the preferred amino acid exchanges at the SALTIN CHCs indicate that Ile → Val is the most frequent replacement found in the direction mesophile Salinibacter ruber recently characterized [Haloferax volcanii [Halophilic proteins have been extensively studied since a long time  and verycterized  shares cvolcanii  displayeArchaea) that utilize the "salt-in" strategy to cope with the strong environmental osmotic pressure, and from halophilic microorganisms using the intracellular accumulation of osmolytes and low cytoplasmatic salt concentration to counterbalance the external osmotic pressure. Proteins synthesized by the "salt-in" organisms are surrounded by a high-salt concentration environment and are in contact with it. At variance, intracellular proteins from the "osmolyte" cells are surrounded by a high concentration solution of compatible solutes which apparently do not interfere significantly with protein solubility, stability and activity [t-test and the non-parametric Wilcoxon test) were used to assess the significance of observed differences of structural parameters. Only differences defined significant according to both tests were deemed bona fide significant signals.Proteins were taken both from microorganisms  that halophilicity of these proteins is directly related to a decrease in the solvent accessible surface. Authors stated that reduction of the solvent accessible area introduced upon mutation causes a progressive destabilization of the molecule, probably due to a reduction in the protein's hydrophobic effect. As a consequence, mutations increasing salt induced stabilization also destabilize the protein in the absence of salt, converting a mesophilic protein into an obligate halophilic form, a trend found in natural halophilic proteins.We noticed that a significant decrease of apolar surface area in the protein synthesized by the halophilic organism can be observed in the OSMOL sample as well, paralleled by an ostensible tendency to increase the presence of side chain oxygen atoms Table . Most ofalinarum  or in anismortui . Thermalismortui . The picismortui  by extenHowever, we did not observe any significant reduction of the accessibility surface (data not shown) in the SALTIN and OSMOL halophilic proteins whereas we noticed the tendency, in the halophilic proteins of the SALTIN samples, to reduce the apolar contact area of the residues exposing more than 25% of their surface. Therefore one could argue that the reduction of hydrophobic effect be a key component of the haloadaptation mechanisms of surfaces.However, surface property variations are not the only feature relevant to protein stability and solubility in high salt environments. Indeed, proper folding of the protein in these conditions requires the formation of appropriate hydrophobic interactions in the interior of the macromolecule. This is supposedly even more important during the early step of protein folding of the nascent polypeptide chain. In this perspective view, we analyzed the variations of apolar contact area in the hydrophobic core of the halophilic SALTIN and OSMOL surface compared to their mesophilic counterparts. No statistically significant difference could be found. Nonetheless, it should be noted that a consistent decrease of the apolar contact area in the halophilic proteins of the SALTIN sample can be observed for core residues at 0% relative accessibility Table . We beliΔΔApAU-F) between each halophilic and non-halophilic pairs display overall no significant difference. This may suggest that, globally, the fraction of apolar area lost during folding is similar in the two cases  although the apolar surface available to the halophilic protein is smaller. This observation is reflected and supported by the significant reduction of exposed apolar area  can provide the theoretical basis for the engineering of proteins of great interest because stable at concentrations of salts that cause the denaturation or aggregation of the majority of macromolecules.http://www.xbase.ac.uk/ and in the literature. The selected organisms have optimal growth conditions that support the presence of genuine adaptation to high salt concentration environments. In fact, those organisms requiring for optimum growth concentration of NaCl < 0.5 M and/or temperatures < 20°C or > 55°C, were excluded from the data sample. Moreover, the organisms were divided into two groups corresponding to different survival strategies: in the first group are the archaeal halophiles using the "salt-in" strategy (which will be referred to as SALTIN sample); in the latter the Eubacteria using the "osmolytes" strategy (OSMOL sample) [The crystallographic structures of the available high salt concentration active enzymes were found in PDB . The sea sample) .http://dunbrack.fccc.edu/PISCES.php[To select only halophilic structures matching specific criteria and to eliminate redundancy, we used the PISCES server ISCES.php, which eISCES.php. To ensuThe apolar contact area is the area of contact between coupled non-polar atoms in a protein. It was calculated for different structural environments: nucleus, interface between monomers and protein surface. The program utilized was Pdb_np_cont , which cIndividual protein chains were used for analysis of the protein core, while analyses of the protein subunit interfaces were carried out with structures in their quaternary assembly. Only the 9 pairs of proteins possessing an oligomeric biological unit were used in this case. Protein interfaces consists of those residues making apolar contacts to another protein chain, as defined by Pdb_np_cont .A residue was assigned to the structural environment "nucleus" if its relative solvent accessibility, calculated with the program NACCESS , is lessFor each structural environment considered the per-residue mean apolar contact area was calculated by dividing the total apolar contact area by the number of residues belonging to that structural environment.i.e. belonging to the classes 7, 8 and 9. These three classes contain the most conserved amino acid positions from a total of nine equally sized categories of relative degree of conservation.Conserved hydrophobic contacts (CHCs) were identified in each pair of homologous enzymes through the combined use of the web tools CE-MC  for calcX, belonging to a non-halophilic protein and involved in making CHCs, aaX→Y was defined as the number of times X is substituted by the residue Y of the halophilic protein. Likewise, aaY→X is defined. Therefore, a substitution matrix can be obtained by computing the difference between aaX→Y and aaY→X over the whole dataset of protein pairs k, according to:Amino acid substitutions of residues involved in the formation of structurally and evolutionarily conserved hydrophobic contacts between halophilic and non-halophilic proteins were determined by analysing the alignment of the SCRs of each pair. For each residue S Cis the element of the substitution matrix.where XY Rof the exchange X→Y was then calculated by dividing the difference between SC, and the overall matrix mean The mean and standard deviation of the overall exchange matrix were determined; the significance XY Rvalues ≥ 3.0 standard deviations (corresponding to a probability P ≤ 0.01 that the observed difference was obtained by chance) from the mean value were considered statistically significant [nificant .http://curie.utmb.edu/getarea.html with default settings [The ASA is the area of the protein surface which can be in contact with the solvent. The total apolar (and the complementary polar) component of the entire accessible surface area of each protein in its quaternary form was calculated with the server GETAREA settings . The conΔApAU-F) were calculated through the web server http://roselab.jhu.edu/utils/unfolded.html[ΔApAU-F in each halophilic protein and in its corresponding homolog (ΔΔApAU-F) were calculated and statistically tested.The differences between the fraction of apolar accessible surface area in the unfolded and folded form of each protein considered  in the SALTIN and OSMOL samples for different class of atoms. The differences are between the surface areas calculated in the halophilic protein and the corresponding areas in the non-halophilic counterpart. The calculations were performed considering the proteins in their quaternary structure. Only residues identically conserved in the two proteins were considered in the calculations.Click here for fileΔΔApAU-FAdditional Figure 1 - . Histograms reporting the ΔΔApAU-F in the SALTIN and OSMOL samples. The ΔΔApAU-F values were calculated as the difference between the fraction of exposed apolar area lost during folding of the halophilic protein and the fraction lost by the corresponding non-halophilic homolog. Further details are reported in the "Methods" section of the main text.Click here for fileΔACA and pairwise percentage identityAdditional Figure 2 - Correlation between single . Graph reporting the difference between the area of each halophilic CHC and that of the corresponding non-halophilic CHC (ΔACA) versus the pairwise sequence percentage identity (%id) for the SALTIN and OSMOL samples.Click here for file


This study investigated the effectiveness of a positive youth development program for Chinese Secondary 3 students in two schools, who had been followed up since their entry to Secondary 1. A mixed research method was carried out using a pre- and post-test pre-experimental design and a focus group for the participants. The subjective outcome evaluations included participants’ perceptions of the program, program instructors, benefits of the program and overall satisfaction, and were positive. The longitudinal data from the objective outcome evaluation showed some notable improvements, and the overall effect of the program was also found to be positive for newcomers in the junior secondary years. The focus group interviews revealed mostly positive feedback in terms of the students’ general impressions of the program, with the majority of participants perceiving benefits to themselves from the program. The findings offer positive evidence of the effectiveness of the program. Macau is a small city located near Hong Kong in South East Asia, famous for tourism and its growing gaming industry. In 2011, the estimated population of Macau was 557,400; it has a comparatively young population, those aged between 10 and 24 making up 21% of the total population . This reA well-structured local youth program can potentially help adolescents’ positive growth and ensure that they are better prepared for future challenges in life. At present, youth studies and theoretically sound and comprehensive programs for adolescent positive growth and development in Macau are lacking , 6. In tHong Kong and Macau share a similar Chinese culture, therefore, the well-tested comprehensive positive youth development program “P.A.T.H.S.,” developed for Chinese students in Hong Kong, was modified and adapted for use in Macau. With support from the Education and Youth Affairs Bureau, a local research team was formed by the author and his colleagues, who modified the program so that the content would reflect the local terminology, such as Macau citizens instead of Hong Kong citizens, government structure of Macau Special Administrative Region instead of Hong Kong Special Administrative Region, some indigenous heritage and customs to suit the local context . The teaMacau has a history of a 15-year free non-tertiary education system, with direct promotion from primary to secondary school without any public examination. Individual admission examination is required after secondary school education for entry into local universities. There is a rather relaxed and less competitive learning atmosphere in Macau’s education system. It is not uncommon to see students repeating their studies in some classes in primary and secondary schools if they find their academic performance unsatisfactory. It is roughly estimated that about 20% of students repeat grades in the junior secondary years in many schools . In thisA mixed research method was adopted for the triangulation of data. It consisted of a quantitative approach using a pre- and post-tests pre-experimental design, together with a qualitative approach using a participant focus group.The two main sources of data were self-reported questionnaires and focus group discussions. The study participants included all Secondary 1 students in the two chosen schools, School A and School B, totally 232 starting in 2009. These students were followed for 3 years up to and including Secondary 3. When this group of students was promoted to Secondary 2, 53 dropped out of their classes and 79 new students joined the program, either to repeat Secondary 2 or because they were transferred from other schools. When the group was promoted to Secondary 3, 41 dropped out and 48 new students were added (Table There were 256 and 240 students who participated in the Wave 5 (W5) pre-test and Wave 6 (W6) post-test respectively. Among the 256 students in the W5 pre-test, 48 18.75%) were new participants. After discarding the questionnaires that were invalid (mainly due to missing data), 236 questionnaires were successfully matched for analysis. Among these 236 students, 142 had joined the program in Secondary 1, 50 in Secondary 2, and 44 in Secondary 3  is a self-administrated questionnaire developed by Shek et al. . It consLife satisfaction is another important indicator of positive youth development . The fivThe five-item scale was used to assess the adolescents’ behavioral intention to engage in problem behavior, including drinking, smoking, taking drugs, having sex, and gambling. The scale was developed by Shek et al.  and has The scale was developed by Shek  and has The Subjective Outcome Evaluation Form (Form A) was designed by Shek and Siu . The ForQuantitative data was collected at two time-points in each year. Firstly, before the program started, the pre-test self-reported questionnaires were completed within 1–2 weeks after the start of the school year. The second data collection time-point occurred at the end of that academic year, after the students had finished the program. The pre-test data Wave 1 (W1) and post-test data Wave 2 (W2) of Secondary 1 were collected and analyzed . The preAt the pre- and post-tests, the participants were invited to complete a valid and reliable questionnaire, including measures of positive youth development, life satisfaction, school adjustment, adolescent problem behaviors, and demographic information. An identical questionnaire was used in the pre- and post-tests. After completion of the program each year, an evaluation questionnaire was also completed by the participants to assess their satisfaction with the course and perceived benefits of the program, providing subjective outcome measures for evaluation.The focus group interview took about 1 h each time. The principal investigator conducted the focus group interview using a semi-structured interview guide provided by the Hong Kong research team.t-test, one-way ANOVA, and repeated ANOVA were performed to examine differences between the scales, providing objective outcome measures for evaluation. Regarding the qualitative data, the content of the interviews was audio-taped with the consent of the participants. It was then transcribed by the research assistant and checked for accuracy by the principal investigator. The raw data of the two groups were analyzed together through coding. After comparison of all the coding, relevant themes were developed.Descriptive statistics were used to present the subjective outcome measures. The paired-samples M = 4.53). The least positive one was overall, I have a very positive evaluation of the program . With regard to the views of the instructors, the most positive response was they felt that the instructors encouraged them to participate in the activities . The least positive one was the instructors’ teaching skills were good .Table M = 3.48). The least helpful one was that it has strengthened their bonding with teachers, classmates, and their family   , LIFE , SA , and BI  scales  Table . To asseThere was one session about how to develop your future. I might be a bit puzzled about my own future. So, the worksheet in that session helped me to establish personal goals and dreams. – From a student in School A.Once I was taught to see things from different angles, I practiced what I had been taught and found that things were really different when you saw them from different perspectives. – From a student in School A.One session talked about romance. If I have to choose a girl or a boy, it is possible that I will remember the principles from that session, and that they will help me to make the right decision. – From a student in School A.It is helpful to manage one’s emotions. We were taught some techniques, such as eating, listening to music, etc. Listening to music helps to release emotions. It has a calming influence. – From a student in School B.My temper has improved somewhat. I remember being taught not to be unhappy due to being angry at others. – From a student in School B.In our age group, dating is common, and we think it is very important. But we do not know how to manage broken relationships. Some even think of committing suicide. Through this program, we learned that even without love from the opposite sex, we still have friendships, and love from our family members. – From a student in School B.Eight students from School A, four male and four female, participated in one of the group interviews. Two were very quiet and seldom responded to the interviewer. Eight students from School B, six male and two female, participated in the other group interview. All were quite responsive to the group discussion. The qualitative findings were mainly analyzed in two areas: the participants’ general impression of the program and perceived benefits of the program to themselves. The preliminary analyses were classified into positive and negative comments on the program. Regarding their general impressions, among the 14 who gave feedback, 4 claimed that they felt bored, lacked time in 1 session, and felt tired toward the end of the day when the program was conducted or the content had been repeated with less input; the rest gave positive responses such as that the content met their daily needs, that it was not as boring as other subjects, that it was interesting, relaxing, interactive, free communication, and an enjoyable small group discussion. The activities that aroused their interest were games, videos, success stories, experiences shared by instructors, and incentives provided during the course. With reference to the perceived benefits, eight students who gave positive feedback asserted that through the program, they had learned how to establish goals for the future, to see things from different angles, to make decisions, to control their emotions, and to develop healthy relationships with others. Some of their narratives were as follows:In this study, the participants’ perceptions of the program and of their program instructors were positive. With regard to their perceptions of the effectiveness of the program and their overall satisfaction, the feedback was also positive. On the whole, the subjective outcome evaluations generally supported positive perceptions of the program, program instructors, benefits of the program and overall satisfaction with the whole course, and these findings were consistent with previous results from the programs for Secondary 1 and 2 in Macau , 12, andWith regard to the objective outcome evaluation, our findings showed that the Secondary 3 program was effective for newly joined participants, with improvements in more than half of the subscales. This was consistent with the findings of the Secondary 2 program, which was also effective for new participants . PossiblAs far as the duration of participating in the program is concerned, joining in either the Secondary 1, 2, or 3 program and using the W6 as the final exit point, no significant differences in the development scales or other measures were found, which shows that participants can join at different times, with a final effective result. The findings revealed both the short- and long-term effects of the 3-year programs on the program participants. In other words, participants can benefit from joining either one, two, or all three programs. On the other hand, there was a significant difference in the problem behavior intention. Participants joining the program for three consecutive years starting from Secondary 1 displayed a lower level of intention to engage in problem behavior than did students joining in Secondary 2 and 3, which is also consistent with the studies in Hong Kong  that fouRegarding the general impression of the program, only a few of the participants perceived it to be boring. Most of them found the program more relaxing and interesting than their conventional moral or civics classes or other formal classes. The class was interactive, with a variety of activities and free communication in small groups. They enjoyed games and video shows that were more up-to-date and related to their daily life. It is consistent with the observation of Shek  that onlOn the whole, the program is effective due to its non-academic, informal, and interactive nature, which is more receptive by the adolescents in building up their positive potentials. On the other hand, more attention should be paid to the behavioral intention of having drugs, sex, and gambling, which may be due to the different messages conveyed by the popularity of internet and may not be easily discerned by adolescents nowadays.This study had several limitations. First, only two schools were involved and the sample size was relatively small, raising the potential for sample bias and making any generalization of the findings difficult. Secondly, the present study was based on a one-group pre-/post-test design, which may not be the most appropriate. Other approaches such as the randomized control trial, which can provide a more rigorous design to give more insight into the effectiveness of an intervention program, could have been considered. Thirdly, a comparatively large portion of students dropped out of the program, which may have affected the longitudinal observation and the observation of long-term effects. It would be worthwhile to follow up this portion of students to see if there is any change in scores afterward. Nevertheless, the present study can contribute to an understanding of the potential benefits of evidence-based youth work, and is also a ground-breaking scientific study showing the impact of the P.A.T.H.S. program on the holistic development of Chinese adolescents in Macau.Subjective outcome evaluation highlighted positive results from all participants. The effect of the program from the objective outcome evaluation was found to be positive to both the newcomers and the old students in the junior secondary years. There was also an overall positive feedback from the focus group interviews. Based on the findings from the subjective and objective outcome evaluations and the focus group interviews, it can be concluded that there is positive evidence of the effectiveness of the Secondary 3 program. In addition, the longitudinal data from the objective outcome evaluation did support an improvement from different time spans in the program. It demonstrated that the 3-year P.A.T.H.S. program has both short- and long-term benefits for program participants. However, students who participated in the program for three consecutive years did better than those who took part in only a 1- or 2-year program in terms of the intention to engage in problem behavior. It showed that the Tier 1 program of the P.A.T.H.S. project can help to prevent adolescent problem behavior through promoting positive development. This program is particularly beneficial to the adolescents in Macau since they are more easily to be tempted for gambling as Macau is a world capital for gambling.There are several implications of this study for school health. First, it demonstrates that participating in a youth development program can have both short- and long-term positive effects for personal growth, and that the program can also be a protective factor in preventing adolescent problem behavior. Second, the interactive and non-academic nature of the program can be more easily accepted by participants, especially for Chinese adolescents in Asian countries where teachers are dominant and directive in the Eastern pedagogical culture and academic performance is greatly emphasized . Third, 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.


Computer-automated depression interventions rely heavily on users reading text to receive the intervention. However, text-delivered interventions place a burden on persons with depression and convey only verbal content.The primary aim of this project was to develop a computer-automated treatment for depression that is delivered via interactive media technology. By using branching video and audio, the program simulates the experience of being in therapy with a master clinician who provides six sessions of problem-solving therapy. A secondary objective was to conduct a pilot study of the program’s usability, acceptability, and credibility, and to obtain an initial estimate of its efficacy.The program was produced in a professional multimedia production facility and incorporates video, audio, graphics, animation, and text. Failure analyses of patient data are conducted across sessions and across problems to identify ways to help the user improve his or her problem solving. A pilot study was conducted with persons who had minor depression. An experimental group (n = 7) used the program while a waitlist control group (n = 7) was provided with no treatment for 6 weeks.All of the experimental group participants completed the trial, whereas 1 from the control was lost to follow-up. Experimental group participants rated the program high on usability, acceptability, and credibility. The study was not powered to detect clinical improvement, although these pilot data are encouraging.Although the study was not powered to detect treatment effects, participants did find the program highly usable, acceptable, and credible. This suggests that the highly interactive and immersive nature of the program is beneficial. Further clinical trials are warranted.ClinicalTrials.gov NCT00906581; http://clinicaltrials.gov/ct2/show/NCT00906581 (Archived by WebCite at http://www.webcitation.org/6A5Ni5HUp) Until now, one commonality among computer-automated depression interventions has been a heavy reliance on users reading text to receive the intervention. However, these interventions have not fully exploited the capacity of computers to deliver interactive media  to guidePrograms can be designed to respond to users’ inputs by playing video and audio clips, based on branching algorithms, to guide users through evidence-based treatments. Such programs could deliver some of the nonspecific aspects of therapy by conveying an on-camera therapist’s warmth, personality, compassion, and ability to remain supportive when the patient experiences setbacks .ePST) for depression and is designed to simulate the experience of being in treatment with a master clinician. It also reports a pilot study that was conducted with 14 persons with minor depression.The purpose of this study was to explore the possibility of using interactive media—particularly video—to deliver computer-automated treatment for depression. This paper describes an interactive multimedia program that provides an automated electronic version of problem-solving therapy . PST-PC has been demonstrated to be effective for the treatment of depression [The pression -5. (For pression .) The baThe mechanism by which problem-solving treatment works has not yet been clearly identified . PST-PC ePST. The goal of ePST was to automate an empirically supported treatment and to provide it in the context of a simulated helping relationship. The ePST program was built for the US National Aeronautics and Space Administration (NASA) as part of a suite of self-guided programs to help astronauts manage their own psychosocial problems on long missions [ePST was funded by NASA, it was designed to also be evaluated among the public with a wide variety of patients. Therefore, a NASA and a general public version were produced, which differ only by a few video clips. As such, ePST is intended for use by both astronauts and nonastronauts.An interactive media program was produced to deliver missions . The sysePST is based on the Virtual Practicum Model [ePST builds on the Virtual Practicum Model by providing persons seeking treatment for depression an opportunity to receive treatment (in a simulated fashion) from a master clinician (author MTH) who is an expert in problem-solving treatment. However, not only does the on-camera clinician walk the user through the concrete steps of problem-solving treatment, he conveys warmth and empathy—the soft skills of a skilled psychotherapist. The goal of both the VPM and ePST is for users to receive training or treatment from an expert in the field, and thereby to increase the number of persons who can benefit from that professional.um Model ,13, an aum Model , Kolb’s um Model , and Schum Model . The Virum Model , manage um Model , and conum Model . The basePST is a multimedia-based, video-intensive program that simulates therapy based on the PST-PC treatment manual [t manual . It inclt manual  measure The first session provides psychoeducation about depression and the process of problem-solving treatment; subsequent sessions offer decreasing guidance on the process of problem-solving treatment. During each session, the virtual therapist guides users through all steps of problem-solving treatment, plus making a list of enjoyable activities (entering their own or choosing from an extensive list of common activities) and scheduling them for the week.Sessions 2 through 6 begin with a check-in on all active problems. The therapist provides feedback about the user’s success or failure in solving problems compared with the previous session and helps him or her identify ways to improve problem solving, both on individual problems and in general.Although the process of problem solving remains consistent throughout the program, a variety of audio and video clips are used to maintain a sense of novelty in each session and to respond to user inputs. At the end of the treatment session, the program produces a printout that summarizes the work the user has done on each problem, including his or her action plans, plus a day-by-day schedule of enjoyable activities for the coming week.ePST.The program’s interfaces are designed for ease of use: where free text entry is requested, no other options are available to the user; where menus are used, five or fewer choices are generally made available. Nonetheless, in the background a highly complex program is running, with substantial branching of video and audio, failure analysis algorithms, and data handling methods that adapt to the user’s clinical status and problem-solving history within ePST by addressing these three domains: (1) the program was designed to be simple to use and went through initial usability testing by persons who had been treated for depression, (2) familiar brands are referenced in the program , and (3) the video and audio for ePST were produced in a broadcast television facility, meeting industry standards for production values, and ePST’s interfaces were developed by professional graphic artists.Fogg and colleagues have identified factors that engender users’ trust in software or websites and found that the credibility depends largely on three factors: (1) the usability of the program , (2) the brand or source behind it, and (3) the professionalism of the interface and media ,22. If aePST can readily be adapted for delivery via the Internet.The initial version of the program was delivered via universal serial bus flash drive, which is a convenient format for astronauts, since they often train in settings without Internet access, and bandwidth on space missions is limited. However, ePST advances the field of computer-automated interventions for depression by (1) approximating actual treatment via the use of rich media, (2) minimizing the amount of text that a user needs to read, and (3) performing failure analyses to assist users to improve their problem-solving effectiveness.ePST program feel more like interacting with a person than with a computer. ePST contains 148 video and 225 audio clips, although each user receives only a fraction of them, based on his or her clinical status and what he or she does in the program.Information richness refers to “the potential information carrying capacity of data” . Media cePST was created for one of the most highly educated groups of individuals in the world—astronauts—it requires less reading skill than most self-help programs, due to the extensive use of audio and video. Text on the screen is written at a low literacy level, mainly limited to labels and occasional short sentences. The user does need to be able to input free text to write his or her own problem statement, goals, and action plan; however, proper grammar and spelling are not required. The writing skill necessary is comparable to that required for sending text messages or emails.Although ePST is to guide users through the process of problem-solving treatment while simultaneously teaching them how to evaluate and improve their own work. Failure analysis is a process of examining failures, identifying reasons for them, and planning how to prevent them in the future. It is used in engineering [ePST, the computer assists users to identify ways to improve their problem solving in general and where to revise work on specific problems, much as a live therapist would do. In this way, ePST tailors each session to what the user has done in the program, thus far.In in-person problem-solving treatment, a therapist guides the client and provides feedback on how he or she could improve on problem solving. However, without a therapist, the challenge of ineering , businesineering , and sofineering ,29. ThroePST. As such, we posed the following research questions, noting that the number of participants would likely not be sufficient to test hypotheses: (1) To what extent do participants find ePST to be usable? (2) To what extent do participants find ePST to be acceptable and credible? and (3) To what extent do participants who use ePST  improve in depression, compared with those who do not use it?The primary purpose of the pilot study was to test research methods and collect preliminary data on which to base a larger clinical trial of We conducted a feasibility study to establish the methods to be used in a future clinical trial and to elicit initial reactions to the program. The study was conducted at the General Clinical Research Center at Beth Israel Deaconess Medical Center in Boston, MA, USA, and was approved by its institutional review board.Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR) [Because there are fewer than 100 astronauts  (and mosM-IV-TR)  criteriaM-IV-TR) .Exclusion criteria were a history of bipolar disorder or schizophrenia, current substance abuse or dependence, dysthymic disorder, or neurological disorders. Study participants with active suicidal ideation, self-injurious behavior, or previous suicide attempts were also excluded.We sent 500 email messages to persons listed on a registry of those interested in receiving information about clinical trials for depression. Of these, 104 persons responded. A total of 54 phone screening interviews  were successfully completed. Others did not respond to messages. Of the 54 persons screened, we excluded 40 . All persons excluded from the study were provided a list of referrals for treatment. This left 14 individuals, who were invited for in-person evaluation. All 14 met eligibility criteria and were enrolled in the study. We randomly assigned 7 participants to each condition.ePST experimental groups using block randomization to ensure equal numbers of participants in each group. Because the number of available participants was small, we made no attempt to balance groups on any variable.We conducted the Mini-International Neuropsychiatric Interview (MINI)  to estabePST condition were requested to use the program weekly on site at the clinic, although they were permitted to schedule sessions less frequently. However, we decided a priori that a longer than 3-week interval between sessions would be considered a protocol violation. We contacted persons in the waitlist (control) group 3 weeks after enrollment to assess depression and safety. A follow-up assessment of depression was conducted at week 6 for control group participants and at posttreatment 1 week after the final ePST session  for ePST group participants. We conducted an additional follow-up with those in the ePST group 4 weeks after they completed ePST. Participants received payment based on the number of times they were required to visit the clinic: nine times for the ePST participants for a total of US $470 and twice for the waitlist participants for a total of US $170. Following the week 6 assessment, waitlist participants were offered off-study use of the ePST program.Participants in the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised, diagnosis of major depression, with Cohen kappa of 0.84, and sensitivity (0.96), specificity (0.88), positive predictive value (0.87), and negative predictive value (0.97) likewise strong [The MINI is a short structured diagnostic interview for DSM-IV-TR psychiatric disorders . The MINe strong . We usedThe HDI  is a selr = .96), and strong convergent validity with the clinician-administered HDRS (r = .95) and the self-administered Beck Depression Inventory (developed by Beck and colleagues in 1961) (r = .92). Factor analysis showed an expected loading of the majority of items on one factor characterized as “depressed mood-demoralization,” which accounted for 43% of the variance in the measure [The HDI shows strong internal consistency , strong test–retest reliability  is a 10-item self-report measure of the ease of using computer programs ,37. ItemePST participants.The Credibility Questionnaire (Cred-Q) is a 9-item survey created for this study from several sources. It comprises questions from the research of Fogg and colleagues ,38 used ePST self-guided treatment program. This instrument included 16 statements  that the user responded to on a 7-point scale, which ranged from 1 (strongly disagree) to 7 (strongly agree).The Assessment of Self-Guided Treatment (AST) is an unpublished measure  that we adapted for this study to assess the acceptability of the ePST program and at 1- and 4-week follow-ups after completing ePST. The SUS was completed after sessions 1 and 6, the Cred-Q after session 5, and the AST after session 4.Participants completed the HDI before using the ePST and refine the evaluation procedures, the number of participants was based on resources available, not on a power analysis. For the pilot study, due to the small sample size, nonparametric statistical analyses were conducted on all measures. These included the Wilcoxon signed rank test and the Mann-Whitney U test. Cronbach alpha was calculated for Cred-Q and AST. The numerical values are presented with mean (SD) or median (range), or both. We used the Statistical Analysis Software (SAS) program, version 9.3  for the analysis.We recruited a sample of 14 participants, 7 per group. Because the primary aims of this evaluation were to gauge the usability and acceptability of As ePST group at pretreatment were 15.61 (SD 9.64), and the median score was 15.4 (range 3.2–31.1). For the waitlist control group, the mean HDI score was 18.71 (SD 6.65) and the median was also 15.4 (range 11.4–26). A Mann-Whitney U test indicated no significant difference in HDI scores between the groups (P = .62) at baseline. We did note demographic differences between the groups  and the subset completing treatment according to the protocol (n = 11). The mean time to complete each session was 53 (SD 31) minutes, with earlier sessions running longer than later ones.One participant in the control group was lost to follow-up. All ePST group completed the SUS after session 1 and session 6. On the 100-point SUS, the mean score was 80.36 (SD 19.28) and median was 85 (range 42.5–97.5) after session 1. After session 6, the mean SUS was 85.36 (SD 15.91) and median was 95 (range 57.5–100). No significant difference was found for the SUS between the two time points .The Cronbach alpha was .922 for the Cred-Q and .830 for the AST. Nonetheless, since the Cred-Q was created for this study and since data have not been previously published on the AST, an item-level analysis of those questionnaires is more appropriate than summary data. Mean and median scores for each Cred-Q item are presented in ePST was 8.81 (SD 5.91) and median was 6.3 (range 1.1–16.7) at posttreatment. For the ePST group, the mean percentage change in HDI score from baseline to posttreatment was –35.86% (SD 40.16%) . The mean HDI score for the waitlist control group at 6-week follow-up was 17.78 (SD 7.52) . The mean percentage change in depression for the control group was –11.12% (SD 18.70%) . A Wilcoxon signed rank test indicated that depression scores remained stable at 4-week follow-up for the ePST group (P = .90), as depicted in At posttreatment, in the intent-to-treat analysis (n = 7), the mean HDI score for persons who received ePST treatment group, depression decreased by an average of 52.65% (SD 28.28%) . There was no significant difference in depression level between 1-week and 4-week follow-ups in the completer analysis . A Wilcoxon signed rank test indicated that depression scores remained stable at 4-week follow-up for the ePST group (P = .90), as depicted in Persons who completed treatment with no more than a 3-week gap between any sessions showed a trend toward greater improvement in depression. For this subset of the ePST is designed to simulate the therapy experience and to feel more like interacting with a person than with a computer. These efforts appear to have paid off, with high scores for usability, credibility, and acceptability in the pilot study. Although efficacy remains to be tested in larger studies, ePST appears to be a promising approach to the treatment of depression.We developed an interactive multimedia computer program to provide problem-solving treatment for depression. The program is entirely automated and does not require the involvement of a live clinician. Nonetheless, Usability describes the ease of use of software or other technology. In a review of 206 studies that used the SUS, the average usability score was 70.14 (SD 21.70) [D 21.70) , with thePST were 8 and 9, respectively, which suggests similar credibility for the ePST program and live clinicians; however, this comparison needs to be further explored in future clinical trials. Ratings on the Cred-Q suggest that participants found the program to be credible for treating their depression. In comparison, Thornett and Mynors-Wallis  conducteePST to be acceptable. Of particular note were answers  to the items “Doing problem-solving treatment using this program was acceptable to me”  and “I would feel comfortable using this program without a clinician’s supervision” .Responses to the AST suggest that persons with depression find ePST program as intended, and gains appeared to have been maintained at 1-month follow-up.Although the pilot study was not powered to evaluate efficacy of the intervention, a decrease in depression scores was noted for persons using the ePST program should be evaluated with a larger sample that includes an active control condition.The clinical evaluation component of this study was secondary to the technology development, in the amount of time and funding devoted to it, and was primarily intended to establish a methodology to evaluate the program in future studies. As such, the feasibility study has many limitations, including the limited sample size and unique characteristics of the sample , inequivalent compensation and assessment time points, and lack of an active control condition. Therefore, given these limitations all conclusions must be considered to be highly preliminary, and the Although we used validated measures wherever possible, none existed for some domains of interest, and we therefore created them. The Cred-Q and AST, which were used for the first time in this study, may have been subject to response set bias. It is notable that most Cred-Q and AST item means are similar to each other, with little variability. Of note are apparently conflicting results to AST questions about preference for using a computer versus being treated by a live clinician: “I would rather do problem-solving treatment with a therapist than with the computer”  and “I would rather use a computer to help myself privately than go to a therapist” . Therefore, the Cred-Q and AST should be revised if used in subsequent studies to better detect response set. Approaches to designing Likert scales to detect and prevent response set have been advanced by Shulruf et al  and BarnFuture studies could directly compare the interactive media approach to delivering problem-solving treatment (which is both bandwidth intensive and costly) versus a text-based version that functions using the same logic. This could determine the merit of using interactive media, compared to the cost to produce and deliver it.ePST is warranted; however, the question is what the best design for such as study would be. Historically, computer-automated behavioral interventions have generally been compared with a waitlist (as in this study), usual care, or live therapy. However, there are drawbacks to each of these designs. Some treatment is likely to be better than no treatment, making a waitlist control a straw man . Usual care comparisons may have more real-world applicability, in which participants are randomly assigned to either use ePST or receive treatment as usual. But usual care varies between settings, and even within a single study group may include many interventions, such as receiving medication, intensive therapy, or nothing at all. Therefore, the usual care control is actually an amalgam of multiple types of control groups.Further evaluation of the effectiveness of ePST versus live problem-solving treatment clinicians following the same protocol would establish noninferiority. This type of data would be most useful for clinics deciding whether to deliver problem-solving treatment via computer or a live clinician (and for which patients); however, many settings do not have the resources to hire or train sufficient numbers of problem-solving treatment clinicians to meet the demand for treatment. A more useful comparison might be randomization to either ePST or another automated treatment of depression, now that several exist in the marketplace. Clinics that are unable to hire specialty staff may well be able to provide automated depression treatment, and few head-to-head comparisons of computer-automated depression treatments have been published.Randomized “John Henry”  (man verX% of learners should perform skill Y at level Z.” The interactive media program is then tested and revised in a spiral development model [A limitation across all of the above comparisons is that they evaluate the automated treatment as a static entity and preclude the opportunity for its improvement during the trial. The criterion-based development model proposed by Carter  is a cycnt model  until thePST should be tested using both models.The advantage of the criterion-based development model over randomized trials is that evaluation data are immediately applied to the improvement of the program, maximizing the potential of the program to effect change. Rather than comparing treatment conditions, which may yield statistically, but not clinically, significant differences, evaluation group outcomes are compared with predetermined, objective standards of health and functioning. It is possible to test whether this meaningful goal is met or exceeded. Clearly there is a need for both randomized trial and criterion-based evaluations, and ePST could tailor the program to special populations, such as cancer patients, older persons, or adolescents. To increase accessibility, a range of hosts could be provided, to better match the user’s demographics, including his or her language.Further development of ePST was designed to overcome some limitations of current computer-automated therapies, such as reliance on text, limited interactivity, and little if any feeling of human connection. In doing so, it presents a model for next-generation interactive, media-based interventions.Although other computer-automated treatments for depression have previously been developed and shown to be effective, that does not mean work in the field should stop, any more than drug discovery should cease once an effective medication has been found for a disease.


Although social skills training programs for people with high-functioning autism (HFA) are widely practiced, the standardization of curricula, the examination of clinical effectiveness, and the evaluation of the feasibility of future trials have yet to be done in Asian countries. To compensate for this problem, a Japanese pilot randomized controlled trial (RCT) of the Treatment and Education of Autistic and Related Communication Handicapped Children (TEACCH)-based group social skills training for children with HFA and their mothers was conducted.Eleven children with HFA, aged 5–6 years, and their mothers were randomly assigned to the TEACCH program (n=5) or a waiting-list control group (n=6). The program involved comprehensive group intervention and featured weekly 2-hour sessions, totaling 20 sessions over six months. The adaptive behaviors and social reciprocity of the children, parenting stress, and parent–child interactions were assessed using the Strengths and Difficulties Questionnaire (SDQ), Parenting Stress Index (PSI), Beck depression inventory-II (BDI-II), and Interaction Rating Scale (IRS).Through this pilot trial, the intervention and evaluation of the program has been shaped. There were no dropouts from the program and the mothers’ satisfaction was high. The outcome measurements improved more in the program group than in the control group, with moderate effect sizes . This pilot trial also implied that this program is more beneficial for high IQ children and mothers with low stress than for those who are not.We have standardized the TEACCH program, confirmed the feasibility of a future trial, and successfully estimated the positive effect size. These findings will contribute to a larger trial in the future and to forthcoming systematic reviews with meta-analyses.UMIN000004560 Children with high-functioning autism (HFA) are included within the autism spectrum disorders axis and within normal ranges of intelligence and language functioning, but have impaired cognitive functioning, social skills, and adaptive behaviors. One of the core symptoms of HFA is difficulty in developing friendships due to deficits in sharing emotional experiences and understanding others’ perspectives. BehavioThe National Autism Center’s National Standards Report, based on a comprehensive review, recogniA recent Cochrane systematic review on SST in individuals with autism aged 6 to 21 years identifiAlthough SST programs or the TEACCH program for people with HFA are widely practiced in clinical or classroom settings in Japan, neither standardization of the curricula nor examination of the effectiveness has as yet been done. This maThus, we conducted this pilot RCT to develop a TEACCH-based group SST program for Japanese children aged five to six years with HFA for the following purposes: To standardize the curricula and outcome measures, to identify the characteristics of persons for whom this program was effective, to evaluate the feasibility of a future trial, and to estimate the effect size of this program.Participants were recruited by mail and telephone from a group including all children and their families who were assessed at a Japanese medical center that specializes in autism and who were eligible according to the inclusion criteria below. We obtained informed consent from the families who joined the study.Children aged five to six years (one year before entering elementary school) whose diagnoses were autism spectrum disorders confirmed by child psychiatrists : F84.0), normal intelligence (IQ ≥75), and moderate severity of autism characteristics (CARS-TV ≥25) were included in the study. Exclusion criteria were as follows: 1) Children with severe psychiatric comorbidities ; 2) Mothers with mental illness with a major obstacle in daily life .TEACCH-based group SST program. The TEACCH approach has been widely practiced in Japan since the 1980s, both in clinical and educational settings. The present program was one that had been done in a specialized autism medical center in Osaka, Japan. The program focused on both children with HFA and their mothers. The program involved comprehensive group intervention in the center and featured weekly 2-hour sessions, totaling 20 sessions over six months. The program providers were two psychologists who were trained in TEACCH methodology and had over five years experience, two nursery teachers, one with one year and the other with 15 years of experience with the TEACCH program, two social workers, and two graduate students studying psychology. A psychologist, who served as advisor for the program for over 20 years, supervised the intervention.Under the program, children were separated from their mothers. An investigator in this study (KI or HY) observed the program from the next room through a one-way mirror and monitored the program by video. The investigator was not directly involved in the program or outcome evaluation. Each session of the children’s program followed the same format:• Warm-up: To monitor the children’s condition (20 min)• Description of the rules: To confirm the rules of the program and present the day’s schedule (20 min)• Game: To practice playing with other children and to learn to understand the rules and the feelings of other children (10 min)• Social Skills Training: See Table • Exercise: To relax (10 min)• Reward and feedback: To provide feedback and strengthen learning (20 min)• Feedback to mothers: To understand their children’s characteristics (10 min)Table Waiting-list control group. Group meetings for mothers were held three times (once every two months) with two social workers for 30–60 minutes per session. The contents of the meetings were not specified or directed by the investigators. After a 6-month non-intervention period, the TEACCH-based SST program was also provided to the control group.[[Baseline demographic characteristics included the children’s profiles and family characteristics: The child’s age, sex, IQ, severity of autism, social competence, disabilities of their siblings, experience in special education programs, mothers’ age, profession, parents’ level of education, use of medical subsidies for infants and children, and educational support for children. DQ was measured by K-test, which w[,15. Soci[, which w[.Primary outcome: SDQ. Strengths and Difficulties Questionnaire (SDQ) measuresSecondary Outcomes: PSI, BDI- II, IRS. The Japanese version of the Parenting Stress Index (PSI),21 measuWe examined the feasibility of a future trial by use of questionnaires that assessed the causes of dropout and mothers’ satisfaction with the contents of the program. We also investigated the mothers’ satisfaction with the length of the session, the duration of intervention, and the frequency and cost of the program, as well as any adverse events or burdens associated with the program.We also described the baseline characteristics of each child in the intervention group to determine the characteristics of suitable participants for this program.Eligible children and their mothers were randomly assigned to an intervention or control group. Children were evaluated both by their mothers and by independent evaluators. The mothers self-reported the condition of their child at baseline and within one month after the end of the intervention (six months after the baseline).After baseline assessments, an independent allocation manager ran a computer-generated allocation schedule based on the following three variables based on the minimization method of balancing three variables: Sex, autism severity (CARS score ≤30 or CARS score >30), and social competence (SQ score ≤100 or SQ score >100). Program providers were unaware of the allocation sequences.To avoid bias, we standardized measurements for assessment and employed independent evaluators and independent allocation managers who were blinded to allocation. However, intervention allocation could not be masked from the children and their mothers in the program or from the program providers.d) was calculated by dividing the baseline SD score of the overall sample by the difference between the intervention and control groups. The sample size required for a future large trial was estimated on the basis of SDQ scores using Stata (version 11.0). Additionally, we analyzed the correlation between the IRS scores of two independent evaluators using Spearman’s rank correlation coefficient. Reporting of the study was complied with the Consolidated Standards of Reporting Trials (CONSORT) statement for non-Pharmacologic Treatment[To evaluate the effectiveness of SDQ, PSI, BDI-II, and IRS, we used intention-to-treat (ITT) analysis and analysis of covariance (ANCOVA). We compared the post-intervention scores between the two groups with baseline scores as a covariate. Because of the pilot nature, no hypothesis testing was employed, but 95% confidence intervals (CI) were described for estimated values. Effect size . There were no monetary incentives for the participants to join the program. This study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000004560).Among 18 families that met the eligibility criteria, five declined to participate given the difficulty of regular participation due to distance (n=2), a subjective burden of the high frequency of the program (n=2), and not feeling the need to participate (n=1). We excluded two families because the children had psychiatric comorbidities: Oppositional defiant disorder. Eleven children were randomly assigned to the program (n=5) or the control group (n=6). Although one family in the program group participated in only 10 sessions due to the mother’s pregnancy, we assessed all participants at the end of the program : Six families completed all 20 sessions, two families completed 19 sessions, one family completed 18 sessions, one family completed 15 sessions, and one family completed 10 sessions (due to the mother’s pregnancy). Regarding program satisfaction, seven families (64%) were satisfied with the overall program, 10 (91%) with the length of each session, nine (82%) with the frequency of the program, eight (73%) with the duration of intervention, and eight (73%) with the cost of the program. Eight families responded that they would recommend this program to others. Nine families responded that they did not have enough time to practice TEACCH in their daily lives. The preferred aspects of the program were "peer counseling (n=11)", "watching the children’s program (n=6)", "parent training (n=6)", and "making manuals for children (n=5)". No adverse events occurred during the program.The difference in SDQ scores between the intervention and control groups at the endpoint was -3.12 (effect size =0.71). The difference in PSI scores was -18.12 (effect size =0.58) and in BDI-II scores was -2.77 (effect size =0.40). The difference in IRS scores  was 2.72 (effect size =0.69). Detailed differences in each participant’s score between baseline and endpoint are shown in Figure The characteristics of child (ID7) whose SDQ score was remarkably improved are as follows: High IQ score (DQ 117), mother with low subjective stress, and no siblings with disabilities. The characteristics of child (ID2) whose SDQ score was moderately improved are a mother with low subjective stress and no siblings with disabilities. The characteristics of child (ID8) whose SDQ score was not improved are as follows: Mother with high stress, siblings with disabilities, and female gender. The characteristics of child (ID9) whose SDQ score was not improved are a low attendance rate at the program, siblings with disabilities, and the mother’s low satisfaction with the program. Concerning child (ID5), the effectiveness of intervention was not clear because this child attended only half of the program due to the mother’s pregnancy.p value of 0.05 and an 80% power calculation.Correlations between the IRS scores of the independent evaluators were ρ=0.70 for the child IRS score, ρ=0.36 for the parent IRS score, and ρ=0.56 for the total IRS score. The required sample size for a future trial was estimated to be approximately 50, allowing for 10% attrition, with a two-sided This is the first RCT to evaluate the TEACCH-based group social skills training program for Asian children aged five to six years with high-functioning autism and to reveal the feasibility and potential efficacy of this program. Koenig reported that "parents wished for more direct feedback with what was taking place in the group sessions in order to follow up with skill-building at home". We askeThe effect of the program was quite satisfactory with regard to the children’s adaptive behaviors, social reciprocity, parenting stress, and parent–child interactions. Because the sample size required for a future trial was estimated to be approximately 50 participants, recruitment of participants at multiple facilities similar to the present one is required.Additionally, the characterization of each child in the intervention group suggested that this program was more effective for the participants whose IQ was high or who had no siblings with disabilities, but was not effective when the mother was heavily stressed. Specialized individual programs may be needed for children with stressed mothers or for lower DQ children. The baseline scores of SDQ and BDI-II revealed that children with HFA had more difficulty in adapting to society and that their mothers were more depressed than their general counterparts. The mothers requested that the program be longer and asked for continuous support after the program. This suggests that we should verify the optimum length of the program in future trials to address this issue.There are some limitations with this study. First was the lack of blindness because the primary outcome (SDQ) was evaluated by participating mothers. To date, there is no objective measure of children’s social skills in Japan. To compensate for this, we used independent rater outcome (IRS) to assess secondary outcomes. High agreement between measurements by two independent evaluators indicated little possibility of serious bias in the present evaluation. The second was limited sample size. The present trial was a pilot of which the primary purpose was not to test a hypothesis but to standardize the program, examine its feasibility, and to estimate potential effect size. Because randomization was strictly conducted and reported in accordance with the CONSORT statement, the present trial was successful and will lead to a relevant larger trial and forthcoming systematic reviews with meta-analyses.This pilot study confirmed the feasibility and potential efficacy of TEACCH-based social skills training in Asia. High-functioning children with autism were able to develop social skills and reciprocity, and their mothers’ stress was reduced. This trial also implied that this program may be especially effective for high IQ children and mothers with low stress. It will contribute to a larger trial in the future and to forthcoming systematic reviews with meta-analyses.This study was funded by a grant from the Meiji Yasuda Mental Health Foundation in 2011. The foundation had no role in data collection, analysis or interpretation of the study. We declare that we have no conflicts of interest.KI conceived this study and performed the study design and the statistical analysis. YT and TI and TN participated in the design of this study and helped to draft the manuscript. MA made the computer based random allocation system. TA developed the Interaction Rating Scale (IRS) and trained the independent evaluators. HY coordinated and observed the intervention to check the feasibility of intervention. All authors read and approved the final manuscript.


Attrition is a persistent issue in online self-help programs, but limited research is available on reasons for attrition or successful methods for improving participant retention. One potential approach to understanding attrition and retention in such programs is to examine person-related variables  that influence behavior. Theoretical models, such as the Theory of Planned Behavior, that describe conditions influencing human behavior may provide a useful framework for predicting participant retention in online-based program.We examined predictors of participant retention in a guided online anxiety, depression, and stress self-help program for university students using the theory of planned behavior. We also explored whether age, symptom severity, and type of coaching  affected participant retention.65 university students with mild to moderate depression, anxiety, and stress were enrolled in this prospective cohort study. Participants completed a questionnaire based on the theory of planned behavior prior to commencing the online-based program and the Depression Anxiety and Stress Scale (DASS) during the assessment module of the program. Participant retention was operationalized as the number of program modules completed.F3,62=6.7; P=.001; adjusted R2=.2; standardized beta=.436, P=.001). Age  and perceived behavioral control  predicted the number of program modules completed . Initial level of distress  did not predict participant retention (P=.55). Participants who chose phone-based coaching completed more program modules than participants who chose email-based coaching .Perceived control over completing the online program significantly predicted intention to complete the program  were found to influence retention in this online-based program. Online self-help programs designed to assist individuals with mental health concerns have been demonstrated to be effective at improving mental health outcomes ,2. DespiThere is currently little known about successful approaches for improving retention in online programs. Studies using guided Internet programs  have reported relatively lower dropout rates compared to unguided programs . HoweveThere is limited research available on predictors of attrition from online programs. The few studies examining this issue have focused primarily on sociodemographic factors , disorder characteristics , and/or treatment-related variables  ,12-15. TAn alternative approach to understanding attrition is to examine person-related factors  that influence the behavior. One theory that attempts to identify predictors of behavior is the Theory of Planned Behavior ,17. ThisThe present study aimed to investigate predictors of participant retention using the theory of planned behavior. We prospectively examined how participants’ attitudes, subjective normative beliefs, and perceived behavior control predict intention to complete a guided online anxiety, depression, and stress self-help program for university students. We then examined whether intention and perceived behavior control successfully predict participant retention in the program. Finally, given the literature examining sociodemographic, disorder characteristics, and treatment-related variables on attrition, we explored whether age, symptom severity, and type of coaching  affected participant retention.Participants were recruited from Dalhousie University, the University of King’s College, and Nova Scotia College of Art and Design, in Halifax, Canada. Recruitment for the study began in 2010. Participants were recruited primarily via emails, advertisements in a campus newspaper, and recruitment posters. Interested individuals contacted the primary program coach through email and were provided with information regarding the study. The study protocol was initially presented to participants on the website’s consent form page. Interested participants signed up for the program online and received a phone call from the primary program coach, who reviewed the consent form with the participant and assessed their eligibility for the study. Participants who provided verbal and written informed consented and met study criteria were included in the study.All participants provided informed consent following procedures approved by the Dalhousie University Research Ethics Board. Eligible participants met the following criteria: (1) experiencing mild to moderate levels of anxiety, depression, or stress, (2) not experiencing suicidal thoughts, (3) not experiencing symptoms of bipolar disorder, an eating disorder, an addiction, or psychosis, and (4) not receiving psychological counseling. Eligibility for the study was assessed through a phone conversation with the participant and the program coach. In total, 68 university students attending the aforementioned postsecondary institutes were assessed for eligibility. Three were excluded due to not meeting eligibility criteria , and 65 were enrolled to participate in the study. From this sample, 48 subjects were also participants in a controlled clinical trial of the online self-help program, and for this reason, 24 participants experienced a 6-week delay in accessing the program due to being randomly assigned to a delayed access control condition. However, all participants, regardless of assignment, completed all measures  immediately prior to commencing the program see .The Theory of Planned Behavior Questionnaire see  is a briThe DASS-21  is an abAll participants who met eligibility criteria and provided written consent were asked to complete the Theory of Planned Behavior Questionnaire via email prior to commencing the guided online self-help program. For participants who received immediate access to the program, the questionnaire was collected immediately prior to beginning the program modules. Participants who were given delayed access to the program, as part of the randomized control trial, completed the questionnaire 6-weeks post assignment . Hence all participants completed the questionnaire immediately prior to commencing the program. The DASS-21 was completed as part of the Introduction and Assessment Module. Delayed access participants completed the DASS-21 for a second time (6-weeks post assignment) as part of the first module .This is a cognitive-behavior therapy-oriented online self-help program developed at Dalhousie University to assist students experiencing mild to moderate anxiety, depression, and stress. It consists of 5 core modules , who contacted them via telephone or email (based on the participants’ preference) on a weekly basis. On average, contact with a coach involved one phone call or one email a week. Phone calls were on average 15-20 minutes in duration, while emails were on average 250-500 words in length. Participants were informed during the consent process that the program coaches were not professional counselors. Program coaches did not function as individual therapists; rather, they provided motivational support to participants and clarified information contained within the program. Coaches also monitored participant progress and reviewed activities completed by participants to ensure the correct applications of the techniques.Program coaches were trained on the online self-help program by the primary investigator, Dr. Victor Day, as well as the head program coach. The majority of the training involved reviewing the online program materials in order to adequately address participant questions and provide assistance with module activities, when necessary. Program coaches were supervised by the head program coach and the primary investigator in order to assure fidelity to the coaching model.The data were analyzed using the statistical software package SPSS 17.0. A planned multiple regression was conducted to investigate whether participants’ attitudes, subjective normative beliefs, and perceived behavioral control predicted their intention to complete the online-based program. A planned hierarchical regression was conducted to investigate whether intention, perceived behavioral control, and age predicted participant retention . These analyses were conducted in accordance to the methods utilized by Azjen ,17, FishSee U=439; P=.46). A larger proportion of delayed access participants discontinued the program  compared to immediate access participants . However, this difference was found to be only marginally significant when examined using a chi-square test . When comparing only the subjects who were also enrolled in the concurrent randomized controlled clinical trial, 62.5% (15/24) of immediate access subjects completed all 5 modules, while 20.8% (5/24) of the delayed access subjects completed all 5 modules .A proportion of the sample  completed the questionnaires and online program 6 weeks after enrolling into the study; thus, the potential effect of delayed access on participant retention was examined using a nonparametric Mann-Whitney test. Participants who experienced delayed access completed a similar number of program modules . This was compared to participants who received immediate access , however, only perceived behavioral control was found to significantly predict participants’ intention to complete the guided online self-help program . Thus, participants who endorsed higher perceived behavioral control over completing the online program also endorsed higher intention to complete the program.To examine whether attitudes, subjective normative beliefs, and perceived behavioral control predict participants’ intention to complete the guided online-based program, these variables were entered into a simultaneous multiple regression see . The modF2,62=1.29, P=.28 adjusted R2 =.01; see F3,61=3.20, P=.03, delta R2 =.10). In this combined model, perceived behavioral control  and age  significantly predicted the number of modules completed (see P=.78), suggesting that the presence of age did not moderate the relationship between perceived behavioral control and participant retention. Instead, these two variables in conjunction predict participant retention.A hierarchical multiple regression was employed to examine factors that may affect participant retention, defined as the number of program modules completed. Intention and perceived behavioral control were entered in the first model since these two variables are proposed to predict behavior  according to the theory of planned behavior . Age waseted see . A folloF3,61=7.14, P=.55, adjusted R2 =-.01.Initial level of distress , as measured by DASS scores, did not predict the number of modules completed: N s; 83% (54/65) of participants chose primarily email-based contact with the program coach. Participants who chose phone-based coaching completed more program modules . This was compared to participants who chose email-based coaching . Participants who chose phone-based coaching did not differ from participants who chose email-based contact on any of the theory of planned behavior variables  or on DASS scores, as examined by a series of Mann-Whitney tests (P>.05).The effect of the type of contact with the program coach on participant retention was examined using a Mann-Whitney test because of unequal group P=.068) and was likely influenced by an unequal number of individuals who experienced delayed access versus immediate access . To examine this further, we compared the completion rates of only the subjects who were concurrently enrolled in the randomized controlled trial (N=48). We found that, in this instance, a greater proportion of immediate access participants  completed all 5 program modules compared to delayed access participants . The result of this subanalysis contradicts previous findings of lower completion rates for individuals in experimental conditions compared with control conditions  of participants did not complete all 5 core modules of the program. Although this represents a large proportion of noncompleters, the percentage of dropouts fell within previously reported ranges ,4 and ma2/65 of pons  and sugAccording to the theory of planned behavior ,17, a peAjzen  asserts Of note is the absence of a predictive relationship between participants’ intention to complete the online program and the number of modules completed. Consistent with this finding, a recent study investigating attrition from an online treatment for chronic insomnia also failed to find a relationship between intention to complete the program and attrition . The lacPrevious literature on attrition from online-based programs has examined sociodemographic, symptom severity, and treatment characteristics. Some studies have found consistent relationships between the degree of symptom severity and participant dropout . In partGuided Internet programs for anxiety and depression have been found to be more efficacious than interventions without treatment support . These bOur study utilized a questionnaire based on the theory of planned behavior, which was designed to be brief and to address our specific hypotheses . Further research is necessary to establish the reliability and internal validity of the items in this questionnaire. In addition, the university students who enrolled in the study were primarily female, and hence gender differences in participant retention could not be examined.This study contributed to the limited literature on predictors of participant attrition and retention in online-based programs. Age, perceived control over completing the program, and the type of coach contact  were found to be important factors in increasing participant retention. Further research is necessary to examine the potential influence of phone-based support versus email support on participant retention. Interventions exploring potential approaches for fostering participants’ perceived behavioral control  may also be helpful in developing strategies to improve participant retention in online programs.