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OBJECTIVES: We examined the effectiveness of the Sources of Strength suicide prevention program in enhancing protective factors among peer leaders trained to conduct schoolwide messaging and among the full population of high school students. METHODS: Eighteen high schools-6 metropolitan and 12 rural-were randomly assigned to immediate intervention or the wait-list control. Surveys were administered at baseline and 4 months after program implementation to 453 peer leaders in all schools and to 2675 students selected as representative of the 12 rural schools. RESULTS: Training improved the peer leaders' adaptive norms regarding suicide, their connectedness to adults, and their school engagement, with the largest gains for those entering with the least adaptive norms. Trained peer leaders in larger schools were 4 times as likely as were untrained peer leaders to refer a suicidal friend to an adult. Among students, the intervention increased perceptions of adult support for suicidal youths and the acceptability of seeking help. Perception of adult support increased most in students with a history of suicidal ideation. CONCLUSIONS: Sources of Strength is the first suicide prevention program involving peer leaders to enhance protective factors associated with reducing suicide at the school population level. [ABSTRACT FROM AUTHOR]

In this article, we present a discussion of two general ways in which the traditional randomized trial can be modified or adapted in response to the data being collected. We use the term adaptive design to refer to a trial in which characteristics of the study itself, such as the proportion assigned to active intervention versus control, change during the trial in response to data being collected. The term adaptive sequence of trials refers to a decision-making process that fundamentally informs the conceptualization and conduct of each new trial with the results of previous trials. Our discussion below investigates the utility of these two types of adaptations for public health evaluations. Examples are provided to illustrate how adaptation can be used in practice. From these case studies, we discuss whether such evaluations can or should be analyzed as if they were formal randomized trials, and we discuss practical as well as ethical issues arising in the conduct of these new-generation trials. [ABSTRACT FROM AUTHOR]

Purpose: The structure of relationships in a social network affects the suicide risk of the people embedded within it. Although current interventions often modify the social perceptions (e.g., perceived support and sense of belonging) for people at elevated risk, few seek to directly modify the structure of their surrounding social networks. We show social network structure is a worthwhile intervention target in its own right., Methods: A simple model illustrates the potential of interventions to modify social structure. The effect of these basic structural interventions on suicide risk is simulated and evaluated. Its results are briefly compared to emerging empirical findings for real network interventions., Results: Even an intentionally simplified intervention on social network structure (i.e., random addition of social connections) is likely to be both effective and safe. Specifically, this illustrative intervention had a high probability of reducing the overall suicide risk, without increasing the risk of those who were healthy at baseline. It also frequently resolved stable, high-risk clusters of people at elevated risk. These illustrative results are generally consistent with emerging evidence from real social network interventions for suicide., Conclusion: Social network structure is a neglected, but valuable intervention target for suicide prevention., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Experiences of child abuse and neglect are risk factors for youth suicidal thoughts and behaviors. Accordingly, suicide risk may emerge as a developmental process that is heavily influenced by the rearing environment. We argue that a developmental, theoretical framework is needed to guide future research on child maltreatment and youth (i.e., adolescent and emerging adult) suicide, and to subsequently inform suicide prevention efforts. We propose a developmental model that integrates principles of developmental psychopathology and current theories of suicide to explain the association between child maltreatment and youth suicide risk. This model bears significant implications for future research on child maltreatment and youth suicide risk, and for suicide prevention efforts that target youth with child maltreatment experiences.

Despite adolescents' suicidal thoughts and behaviors being major health problems, sparse literature exists on the roles of adolescents' disclosing their feelings to caregivers in their suicidal thoughts and behaviors. This study examined whether adolescents' comfort in disclosing their feelings and problems to caregivers predicts subsequent suicidal thoughts and behaviors and whether difficulties in emotion regulation mediate this association. High school students (N = 5,346 from 20 schools, 49% female-identified adolescents, and 35% 9th graders, 33% 10th graders, and 32% 11th graders) participated in the study for two years with four waves, each six months apart: fall semester in Year 1 (Wave 1), spring semester in Year 1 (Wave 2), fall semester in Year 2 (Wave 3), and spring semester in Year 2 (Wave 4). The degree to which adolescents felt comfortable disclosing their feelings and problems to caregivers at Wave 1 predicted lower suicidal thoughts and behaviors at Wave 4 directly and indirectly via higher emotional clarity at Wave 2 and feeling more able to handle negative emotions at Wave 3. Moreover, when female-identified adolescents reported feeling unable to handle negative emotions at Wave 3, they reported engaging in more suicidal thoughts and behaviors at Wave 4 than male-identified adolescents. Therefore, enhancing adolescents' comfort in disclosing their feelings and problems to caregivers and adolescent emotion regulation and taking a nuanced approach to support female-identified adolescents regarding their ability to handle negative emotions could prevent adolescents' suicidal thoughts and behaviors., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Many preventive trials randomize individuals to intervention condition which is then delivered in a group setting. Other trials randomize higher levels, say organizations, and then use learning collaboratives comprised of multiple organizations to support improved implementation or sustainment. Other trials randomize or expand existing social networks and use key opinion leaders to deliver interventions through these networks. We use the term contextually driven to refer generally to such trials (traditionally referred to as clustering, where groups are formed either pre-randomization or post-randomization - i.e., a cluster-randomized trial), as these groupings or networks provide fixed or time-varying contexts that matter both theoretically and practically in the delivery of interventions. While such contextually driven trials can provide efficient and effective ways to deliver and evaluate prevention programs, they all require analytical procedures that take appropriate account of non-independence, something not always appreciated. Published analyses of many prevention trials have failed to take this into account. We discuss different types of contextually driven designs and then show that even small amounts of non-independence can inflate actual Type I error rates. This inflation leads to rejecting the null hypotheses too often, and erroneously leading us to conclude that there are significant differences between interventions when they do not exist. We describe a procedure to account for non-independence in the important case of a two-arm trial that randomizes units of individuals or organizations in both arms and then provides the active treatment in one arm through groups formed after assignment. We provide sample code in multiple programming languages to guide the analyst, distinguish diverse contextually driven designs, and summarize implications for multiple audiences., (© 2022. The Author(s).)

Background: Peer-led interventions for adolescents are effective at accelerating behavioral change. The Sources of Strength suicide preventive program trains student peer change agents (peer leaders) in secondary schools to deliver prevention messaging and conduct activities that increase mental health coping mechanisms. The program currently has school staff select peer leaders. This study examined potential for more efficient program diffusion if peer leaders had been chosen under network-informed selection methods., Methods: Baseline assessments were collected from 5,746 students at 20 schools. Of these, 429 were selected by adults as peer leaders who delivered intervention content through the school year. We created theoretical alternate peer leader sets based on social network characteristics: opinion leadership, centrality metrics, and key players. Because these sets were theoretical, we examined the concordance of these sets with the actual adult-selected peer leaders sets and correlated this metric with diffusion of intervention modalities (i.e., presentation, media, communication, activity) after the first year., Results: The sets of adult-selected peer leaders were 13.3%-22.7% similar to theoretical sets chosen by other sociometric methods. The use of friendship network metrics produced peer leader sets that were more white and younger than the general student population; the Key Players method produced more representative peer leader sets. Peer opinion leaders were older and more white than the general population. Schools whose selected peer leaders had higher overlap with theoretical ones had greater diffusion of intervention media and peer communication., Conclusions: The use of network information in school-based peer-led interventions can help create more systematized peer leader selection processes. To reach at-risk students, delivery of an indirect message, such as through a poster or video, may be required. A hybrid approach where a combination of visible, respected opinion leaders, along with strategically-placed key players within the network, may provide the greatest potential for intervention diffusion., (© 2022. The Author(s).)

U.S. military suicides are increasing and disrupted relationships frequently precede them. Group-level interventions are needed that reduce future suicide vulnerability among healthy members and also ameliorate risk among those already suicidal. We examined whether our Wingman-Connect Program (W-CP) strengthened Air Force relationship networks and socially integrated at-risk members. Air Force personnel classes in training were randomized to W-CP or active control (cluster RCT), followed up at 1 and 6 months (94% and 84% retention). Data were collected in 2017-2019 and analyzed in 2020-2021. Participants were 1485 male and female Airmen in 215 technical training classes. W-CP training involved strengthening group bonds, skills for managing career and personal stressors, and diffusion of healthy norms. Active control was stress management training. Primary outcomes were social network metrics based on Airmen nominations of valued classmates after 1 month. Baseline CAT-SS >34 defined elevated suicide risk. W-CP increased social network integration, with largest impact for Airmen already at elevated suicide risk (n = 114, 7.7%). For elevated risk Airmen, W-CP improved all network integration metrics, including 53% average gain in valued connection nominations received from other Airmen (RR = 1.53, 95% CI = 1.12, 2.08) and eliminated isolation. No elevated risk Airmen in W-CP were isolates with no valued connections after 1-month vs. 10% among controls (P < .035). In contrast to at-risk controls, at-risk W-CP Airmen increased connections after intervention. W-CP's effect on a key indicator, ≥2 connections, was still greater 2-4 months after classes disbanded (6-months). Wingman-Connect Program built enhanced suicide protection into unit relationship networks and counteracted standard drift towards disconnection for at-risk Airmen, despite no explicit content targeting connections specifically to at-risk Airmen. Findings support a growing case for the unique contribution of group-level interventions to improve social health of broader military populations while also ameliorating risk among individuals already at elevated suicide risk., (Copyright © 2022 University of Rochester School of Medicine and Dentistry. Published by Elsevier Ltd.. All rights reserved.)

The current study tested differences in social network characteristics of high school students who report perpetrating sexual violence (SV) versus those who do not. N = 4554 students (49% male, 49% female, 2% another gender identity; 45% Hispanic, 43% white, 12% another racial identity) from 20 high schools reported how often they had perpetrated 13 sexually violent behaviors. Using their responses, students were classified as follows: non-perpetrators, sexual harassment perpetrators, low contact perpetrators, or high contact perpetrators. Students named up to 7 close friends and up to 7 trusted adults at their school and answered questions about other behaviors and attitudes. This information was used to assess (1) students' connections with peers, (2) students' connections with trusted adults, and (3) friends' characteristics. Multilevel models indicated that compared to their peers, high contact perpetrators were less involved in the peer networks, less connected to trusted adults, and more likely to have friends who were involved in risky behaviors (e.g., sexual violence, homophobic name-calling, substance use). Low contact perpetrators were as connected to peers and trusted adults as non-perpetrators but were more likely to have friends engaged in sexual violence and homophobic naming-calling perpetration. By contrast, sexual harassment perpetrators were more involved and held higher status in the peer network (e.g., received more friendship nominations) but otherwise had similar friendship characteristics and similar connections to trusted adults as non-perpetrators. Building on these results, social network-informed SV prevention should use opinion leaders to change SV norms throughout the network and encourage new relationships between low- and high-risk students so as to disseminate norms that do not tolerate SV. Promoting connections to trusted adults also may be a useful avenue, especially for isolated adolescents.Trial Registration This study is registered at www.clinicaltrials.gov NCT01672541. Syntax code is available from the authors upon request., (© 2021. Society for Prevention Research.)

Using social networks to inform prevention efforts is promising but has not been applied to vaping. To address this gap, we pilot tested the peer-led Above the Influence of Vaping (ATI-V) and examined diffusion through 8th grade networks in three schools. Fifty students, nominated and trained as Peer Leaders, implemented prevention campaigns informed by communication science, including gain-loss messaging and social norming. Across schools, 86-91% of students (N = 377) completed measures (pre-post) of electronic vaping product (EVP) use and attitudes, and named close friends and adults to construct social networks. Using baseline reports, we classified students as Recent EVP Users (10%), Vulnerable Nonusers (24%), or Resolute Nonusers (66%). Peer Leaders had reach through friendship connections to students at varying risk of vaping; 12-16 weeks after Peer Leaders were trained and began implementing campaigns, 79% of Resolute Nonusers and 74% of Recent Users/Vulnerable Nonusers reported exposure to a vaping prevention message. Students with more Peer Leader friends were less likely to report recent EVP use (OR = 0.41) or intention to use an EVP (B = 0.12) on post-surveys, supporting the intervention conceptual model positing diffusion through friendship networks. Use of student-nominated peer leaders was supported by network analyses showing EVP Users integrated within the friendship network, having more high-risk friends, and fewer adult connections. This evidence is the first to show that adolescent Peer Leaders with ongoing mentoring and science-informed campaigns can potentially reduce EVP acceptability and use. Areas for refining ATI-V include increasing consistency of campaign exposure across schools., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Importance: Suicide has been a leading manner of death for US Air Force personnel in recent years. Universal prevention programs that reduce suicidal thoughts and behaviors in military populations have not been identified., Objectives: To determine whether the Wingman-Connect program for Airmen-in-training reduces suicidal ideation, depression, and occupational problems compared with a stress management program and to test the underlying network health model positing that cohesive, healthy units are protective against suicidal ideation., Design, Setting, and Participants: This cluster randomized clinical trial was conducted from October 2017 to October 2019 and compared classes of personnel followed up for 6 months. The setting was a US Air Force technical training school, with participants studied to their first base assignment, whether US or international. Participants in 216 classes were randomized, with an 84% retention rate. Data analysis was performed from November 2019 to May 2020., Interventions: The Wingman-Connect program used group skill building for cohesion, shared purpose, and managing career and personal stressors (3 blocks of 2 hours each). Stress management training covered cognitive and behavioral strategies (2 hours). Both conditions had a 1-hour booster session, plus text messages., Main Outcomes and Measures: The primary outcomes were scores on the suicidal ideation and depression scales of the Computerized Adaptive Test for Mental Health and self-reports of military occupational impairment. Class network protective factors hypothesized to mediate the effect of Wingman-Connect were assessed with 4 measures: cohesion assessed perceptions that classmates cooperate, work well together, and support each other; morale was measured with a single item used in other studies with military samples; healthy class norms assessed perceptions of behaviors supported by classmates; and bonds to classmates were assessed by asking each participant to name classmates whom they respect and would choose to spend time with., Results: A total of 215 classes including 1485 individuals (1222 men [82.3%]; mean [SD] age, 20.9 [3.1] years) participated; 748 individuals were enrolled in the Wingman-Connect program and 737 individuals were enrolled in the stress management program. At 1 month, the Wingman-Connect group reported lower suicidal ideation severity (effect size [ES], -0.23; 95% CI, -0.39 to -0.09; P = .001) and depression symptoms (ES, -0.24; 95% CI, -0.41 to -0.08; P = .002) and fewer occupational problems (ES, -0.14; 95% CI, -0.31 to -0.02; P = .02). At 6 months, the Wingman-Connect group reported lower depression symptoms (ES, -0.16; 95% CI, -0.34 to -0.02; P = .03), whereas the difference in suicidal ideation severity was not significant (ES, -0.13; 95% CI, -0.29 to 0.01; P = .06). The number needed to treat to produce 1 fewer participant with elevated depression at either follow-up point was 21. The benefits of the training on occupational problems did not extend past 1 month. The Wingman-Connect program strengthened cohesive, healthy class units, which helped reduce suicidal ideation severity (estimate, -0.035; 95% CI, -0.07 to -0.01; P = .02) and depression symptom scores (estimate, -0.039; 95% CI, -0.07 to -0.01; P = .02) at 1 month., Conclusions and Relevance: Wingman-Connect is the first universal prevention program to reduce suicidal ideation and depression symptoms in a general Air Force population. Group training that builds cohesive, healthy military units is promising for upstream suicide prevention and may be essential for ecological validity. Extension of the program to the operational Air Force is recommended for maintaining continuity and testing the prevention impact on suicidal behavior., Trial Registration: ClinicalTrials.gov Identifier: NCT04067401.

Suicide is a leading cause of death among youth worldwide. The purpose of the current review was to examine recent cross-national trends in suicide mortality rates among 10- to 19-year-olds. This study extracted suicide mortality data from the World Health Organization's (WHO) Mortality Database for the most recent year (since 2010) from any country with available high-quality data (as defined by the WHO's guidelines). Data on access to lethal means (firearms, railways) and measures of economic quality (World Bank Income Group) and inequality (Gini coefficients) were obtained from publicly available data sources. Cross-national suicide mortality rates in youth were heterogeneous. The pooled estimate across all ages, sexes, and countries was 3.77/100,000 people. The highest suicide rates were found in Estonia, New Zealand, and Uzbekistan. Suicide rates were higher among older compared with younger adolescents and higher among males than females. The most common suicide methods were hanging/suffocation and jumping/lying in front of a moving object or jumping from a height. Firearm and railway access were related to suicide deaths by firearms and jumping/lying, respectively. Economic quality and inequality were not related to overall suicide mortality rates. However, economic inequality was correlated with a higher ratio of male:female suicides. This study provides a recent update of cross-national suicide trends in adolescents. Findings replicate prior patterns related to age, sex, geographic region, and common suicide methods. New to this review are findings relating suicide method accessibility to suicide mortality rates and the significant association between income inequality and the ratio of male:female suicide. Future research directions include expanding the worldwide coverage to more low- and middle-income countries, examining demographic groupings beyond binary sex and to race/ethnicity within countries, and clarifying factors that account for cross-national differences in suicide trends., (© 2019 Association for Child and Adolescent Mental Health.)

Background: Strengthening social integration could prevent suicidal behavior. However, minimal research has examined social integration through relationship network structure. To address this important gap, we tested whether structural characteristics of school networks predict school rates of ideation and attempts., Methods: In 38 US high schools, 10,291 students nominated close friends and trusted adults to construct social networks. We used mixed-effects logistic regression models to test individual student networks and likelihood of suicidal ideation (SI) and suicide attempts (SA); and linear regression models to estimate associations between school network characteristics and school rates of SI, SA, and SA among all with ideation., Results: Lower peer network integration and cohesion increased likelihood of SI and SA across individual and school-level models. Two factors increased SA: student isolation from adults and suicidal students' popularity and clustering. A multivariable model identified higher SA in schools where youth-adult relationships were concentrated in fewer students (B = 4.95 [1.46, 8.44]) and suicidal students had higher relative popularity versus nonsuicidal peers (B = 0.93 [0.10, 1.77]). Schools had lower SA rates when more students named the same trusted adults named by friends and many students named the same trusted adults. When adjusting for depression, violence victimization and bullying, estimates for adult network characteristics were substantially unchanged whereas some peer effects decreased., Conclusions: Schoolwide peer and youth-adult relationship patterns influence SA rates beyond individual student connections. Network characteristics associated with suicide attempts map onto three theory-informed domains: social integration versus thwarted relational needs, group cohesion, and suicidal students' social influence. Network interventions addressing these processes, such as maximizing youth-adult connections schoolwide and heightening influence of youth with healthy coping, could create more protective schools. Longitudinal and intervention studies are needed to determine how schools differentiate in network structure and clarify reciprocal dynamics between network characteristics and suicidal behavior., (© 2019 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Training peer leaders (PLs) as implementation agents is a state-of-the-art approach in prevention, but the field lacks frameworks for providing support. Text messaging, a powerful tool for direct intervention, may be useful in this regard. We introduce a conceptual framework for engaging, retaining, and educating adolescent PLs and conduct a pilot test of this framework using text messages for delivery to middle school PLs in a new, peer-led substance use prevention program. Fifty eighth-graders were recruited as PLs. We used a newly-developed framework to create text messages to strengthen peer leaders': (a) mission, agency, and team identity; (b) connection to adult mentors; (c) content knowledge and application to their own lives; and (d) preparation for prevention activities. Thirty-four texts were sent to PLs over 4 months. PL replies and participation were recorded to track engagement. Forty-one PLs (71%) received texts and completed baseline and post-program surveys. Parents and school staff completed post-program questionnaires. Eighty-five percent of PLs responded to at least one text message. Response rates for specific messages varied from 22 to 56%. Students were most likely to reply to texts about preparation for their own prevention activities in the school. Ninety-five percent of PLs said they read messages even when they did not reply. Eighty-three percent of PLs said the messages helped them accomplish their mission. PLs reported that they wanted to receive messages in the future. PL attendance had very little variability in two of the three schools, but replies to texts were associated with better attendance in one school. Our study provides a framework for supporting adolescent peer leaders in a network intervention. Automated text messaging supporting middle school PLs was feasible, engaging, and well-received. Texting activity was associated with participation in school-based activities. Future priorities include systematically varying text support to determine its true effect on implementation and on involvement by less engaged PLs.

Background: Peer-led interventions have been applied to prevent various health behavior problems and may be an important complement to individual-level suicide prevention approaches. Sources of Strength trains student "peer leaders" in secondary schools to conduct prevention activities that encourage other students to build healthy social bonds and strengthen help-seeking norms. Prior work examining diffusion of peer-led programs has focused on youths' closeness to peer leaders but minimally on other factors such as connections to adults and suicidal behavior. Methods: We examined implementation and dissemination of Sources of Strength in 20 schools. Over 1 year 533 students were trained as peer leaders and 3,730 9th-12th graders completed baseline surveys assessing friendships and adults at school, and suicidal thoughts/behaviors; and end-of-year surveys reporting intervention exposure: viewed poster/video, attended presentation, direct peer communication, and activity participation. Chi-square tests compared exposure rates by student and network characteristics. Multi-level logistic regression models tested predictors of exposure across individual and school-level characteristics. Results: Exposure to the intervention varied greatly by school and by individual student characteristics and network position. Training more peer leaders increased school-wide exposure for all modalities except presentation (Bs 0.06-0.10, p's < 0.05). In multivariate models, exposure was consistently higher for students closer to peer leaders in the friendship network (ORs 1.13-1.54, p's < 0.05) and students who named more trusted adults (ORs 1.08-1.16, p's < 0.001); and lower for males (ORs 0.56-0.83, p's < 0.05). In multivariate models, training more students as peer leaders predicted exposure to poster-video and direct peer communication in larger schools (OR = 3.34 and 2.87, respectively). Network characteristics influenced exposure similarly for students with suicidal thoughts and behaviors. Discussion: Our findings confirm prior work showing the importance of personal affiliations to peer leaders and natural networks as a medium for diffusion of peer-led prevention efforts. We build on that work by showing independent effects of closeness to adults at school and number of peer leaders trained. There is a need to strategically select peer leaders to maximize closeness to students school-wide, particularly in larger schools. Additional work is required for Sources of Strength to devise messaging strategies to engage males and students isolated from adults at school.

Background: Suicide is a leading cause of death among 10- to 19-year-olds in the United States, with 5% to 8% attempting suicide each year. Suicide risk rises significantly during early adolescence and is higher in rural and underserved communities. School-based universal prevention programs offer a promising way of reducing suicide by providing strategies for emotion regulation and encouraging help-seeking behaviors and youth-adult connectedness. However, such programs frequently run into difficulties in trying to engage a broad range of students. Text messaging is a dominant medium of communication among youths, and studies show both efficacy and uptake in text messaging interventions aimed at adolescents. Text-based interventions may, thus, offer a means for school-based universal prevention programs to engage adolescents who would otherwise be difficult to reach., Objective: We field tested Text4Strength, an automated, interactive text messaging intervention that seeks to reach a broad range of early adolescents in rural communities. Text4Strength extends Sources of Strength, a peer-led school suicide prevention program, by encouraging emotion regulation, help-seeking behaviors, and youth-adult connectedness in adolescents. The study tested the appeal and feasibility of Text4Strength and its potential to extend universal school-based suicide prevention., Methods: We field tested Text4Strength with 42 ninth-grade students. Over 9 weeks, students received 28 interactive message sequences across 9 categories (Sources of Strength introduction, positive friend, mentors, family support, healthy activities, generosity, spirituality, medical access, and emotion regulation strategies). The message sequences included games, requests for advice, questions about students' own experiences, and peer testimonial videos. We measured baseline mental health characteristics, frequency of replies, completion of sequences and video viewing, appeal to students, and their perception of having benefited from the program., Results: Of the 42 participating students, 38 (91%) responded to at least one sequence and 22 (52%) responded to more than a third of the sequences. The proportion of students who completed multistep sequences they had started ranged from 35% (6/17) to 100% (3/3 to 28/28), with responses dropping off when more than 4 replies were needed. With the exception of spirituality and generosity, each of the content areas generated at least a moderate number of student replies from both boys and girls. Students with higher and lower levels of risk and distress interacted with the sequences at similar rates. Contrary to expectations, few students watched videos. Students viewed the intervention as useful-even those who rarely responded to messages. More than 70% found the texts useful (3 items, n range 29-34) and 90% (36) agreed the program should be repeated., Conclusions: Text4Strength offers a potentially engaging way to extend school-based interventions that promote protective factors for suicide. Text4Strength is ready to be revised, based on findings and student feedback from this field test, and rigorously tested for efficacy., (©Anthony R Pisani, Peter A Wyman, Kunali Gurditta, Karen Schmeelk-Cone, Carolyn L Anderson, Emily Judd. Originally published in JMIR Mental Health (http://mental.jmir.org), 31.05.2018.)

Background: Equipping members of a target population to deliver effective public health messaging to peers is an established approach in health promotion. The Sources of Strength program has demonstrated the promise of this approach for "upstream" youth suicide prevention. Text messaging is a well-established medium for promoting behavior change and is the dominant communication medium for youth. In order for peer 'opinion leader' programs like Sources of Strength to use scalable, wide-reaching media such as text messaging to spread peer-to-peer messages, they need techniques for assisting peer opinion leaders in creating effective testimonials to engage peers and match program goals. We developed a Web interface, called Stories of Personal Resilience in Managing Emotions (StoryPRIME), which helps peer opinion leaders write effective, short-form messages that can be delivered to the target population in youth suicide prevention program like Sources of Strength., Objective: To determine the efficacy of StoryPRIME, a Web-based interface for remotely eliciting high school peer leaders, and helping them produce high-quality, personal testimonials for use in a text messaging extension of an evidence-based, peer-led suicide prevention program., Methods: In a double-blind randomized controlled experiment, 36 high school students wrote testimonials with or without eliciting from the StoryPRIME interface. The interface was created in the context of Sources of Strength-an evidence-based youth suicide prevention program-and 24 ninth graders rated these testimonials on relatability, usefulness/relevance, intrigue, and likability., Results: Testimonials written with the StoryPRIME interface were rated as more relatable, useful/relevant, intriguing, and likable than testimonials written without StoryPRIME, P=.054., Conclusions: StoryPRIME is a promising way to elicit high-quality, personal testimonials from youth for prevention programs that draw on members of a target population to spread public health messages., Competing Interests: Conflicts of Interest: None declared., (©Phyo Thiha, Anthony R Pisani, Kunali Gurditta, Erin Cherry, Derick R Peterson, Henry Kautz, Peter A Wyman. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 09.11.2016.)

Internet-connected devices are changing the way people live, work, and relate to one another. For prevention scientists, technological advances create opportunities to promote the welfare of human subjects and society. The challenge is to obtain the benefits while minimizing risks. In this article, we use the guiding principles for ethical human subjects research and proposed changes to the Common Rule regulations, as a basis for discussing selected opportunities and challenges that new technologies present for prevention science. The benefits of conducting research with new populations, and at new levels of integration into participants' daily lives, are presented along with five challenges along with technological and other solutions to strengthen the protections that we provide: (1) achieving adequate informed consent with procedures that are acceptable to participants in a digital age; (2) balancing opportunities for rapid development and broad reach, with gaining adequate understanding of population needs; (3) integrating data collection and intervention into participants' lives while minimizing intrusiveness and fatigue; (4) setting appropriate expectations for responding to safety and suicide concerns; and (5) safeguarding newly available streams of sensitive data. Our goal is to promote collaboration between prevention scientists, institutional review boards, and community members to safely and ethically harness advancing technologies to strengthen impact of prevention science.

Background: The school system has been identified as an ideal setting for the implementation of prevention and early intervention programs for suicide. However, in Australia, suicide-prevention programs that are routinely delivered in the schools are lacking. Internationally, evidence exists for the effectiveness of peer-led interventions that take a social connectedness approach to improve help-seeking for suicide. The aim of the current trial is to test the effectiveness of the Sources of Strength program to promote help-seeking for suicide in adolescents in Australian high schools., Methods/design: This study is a two-arm, cluster-randomised, controlled trial that will compare the evidence-based Sources of Strength program to a wait-list control condition. Sixteen Australian high schools will be recruited to the trial, with all adolescents in years 7 to 10 (12-16 years of age) invited to participate. Peer leaders from intervention-condition schools will receive training in the Sources of Strength program and will integrate positive messages, across 3 months, with the support of adult advisors. Activities may take the form of class presentations, posters, videos, and messages on social media sites and will aim to change help-seeking norms, strengthen youth-adult connections, and promote positive coping. The primary outcome measure for the study is help-seeking intentions, whereas secondary outcomes include help-seeking behaviour, help-seeking attitudes and norms, referral of distressed peers, availability of adult help, positive coping, and suicidal behaviour. Data will be collected pre-intervention, post-intervention (after the initial 3 months of messaging), and at the end of the first (6-month follow-up) and the second year after implementation (18-month follow-up). Primary analyses will compare changes in help-seeking intentions for the intervention condition relative to the wait-list control condition using mixed-effect repeated-measures analyses to account for clustering within schools., Discussion: If proven effective, this universal social connectedness program for suicide could be more widely delivered in Australian high schools, providing a valuable new resource. The Sources of Strength program has the potential to significantly contribute to the mental health of young people in Australia by improving help-seeking for suicide. The findings from this research will also contribute to the evidence-base for peer-leadership programs internationally., Trial Registration: Australian New Zealand Clinical Trials Registry, ACTRN12616000048482 . Registered on 19 January 2016.

Suicide is a public health problem that accounts for more than 1 million deaths annually worldwide. This article addresses evidence-based and promising youth suicide prevention approaches at the primary, secondary, and tertiary levels. Coordinated, developmentally timed, evidence-based suicide prevention approaches at all intervention levels are likely to reduce youth suicide. For most youth who die by suicide, there are opportunities for intervention before imminent risk develops. Current research in suicide prevention points to the value of investing in "upstream" universal interventions that build skills and resilience as well as policies that enable access to care and protection from lethal means., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In this paper we present and discuss a novel research approach, the baseline target moderated mediation (BTMM) design, that holds substantial promise for advancing our understanding of how genetic research can inform prevention research. We first discuss how genetically informed research on developmental psychopathology can be used to identify potential intervention targets. We then describe the BTMM design, which employs moderated mediation within a longitudinal study to test whether baseline levels of intervention targets moderate the impact of the intervention on change in that target, and whether change in those targets mediates causal impact of preventive or treatment interventions on distal health outcomes. We next discuss how genetically informed BTMM designs can be applied to both microtrials and full-scale prevention trials. We use simulated data to illustrate a BTMM, and end with a discussion of some of the advantages and limitations of this approach.

Developing science-based communication guidance and positive-themed messages for suicide prevention are important priorities. Drawing on social learning and elaboration likelihood models, we designed and tested two positive-focused presentations by high school peer leaders delivered in the context of a suicide prevention program (Sources of Strength). Thirty-six classrooms in four schools (N = 706 students) were randomized to (1) peer leader modeling of healthy coping, (2) peer leader modeling plus audience involvement to identify trusted adults, or (3) control condition. Students' attitudes and norms were assessed by immediate post-only assessments. Exposure to either presentation enhanced positive coping attitudes and perceptions of adult support. Students who reported suicide ideation in the past 12 months benefited more than nonsuicidal students. Beyond modeling alone, audience involvement modestly enhanced expectations of adult support, congruent with the elaboration likelihood model. Positive peer modeling is a promising alternative to communications focused on negative consequences and directives and may enhance social-interpersonal factors linked to reduced suicidal behaviors., (© 2015 The American Association of Suicidology.)

The dynamic wait-listed design (DWLD) and regression point displacement design (RPDD) address several challenges in evaluating group-based interventions when there is a limited number of groups. Both DWLD and RPDD utilize efficiencies that increase statistical power and can enhance balance between community needs and research priorities. The DWLD blocks on more time units than traditional wait-listed designs, thereby increasing the proportion of a study period during which intervention and control conditions can be compared, and can also improve logistics of implementing intervention across multiple sites and strengthen fidelity. We discuss DWLDs in the larger context of roll-out randomized designs and compare it with its cousin the Stepped Wedge design. The RPDD uses archival data on the population of settings from which intervention unit(s) are selected to create expected posttest scores for units receiving intervention, to which actual posttest scores are compared. High pretest-posttest correlations give the RPDD statistical power for assessing intervention impact even when one or a few settings receive intervention. RPDD works best when archival data are available over a number of years prior to and following intervention. If intervention units were not randomly selected, propensity scores can be used to control for non-random selection factors. Examples are provided of the DWLD and RPDD used to evaluate, respectively, suicide prevention training (QPR) in 32 schools and a violence prevention program (CeaseFire) in two Chicago police districts over a 10-year period. How DWLD and RPDD address common threats to internal and external validity, as well as their limitations, are discussed.

Background: Quality of the parent-child relationship is a robust predictor of behavioral and emotional health for children and adolescents; the application to physical health is less clear., Methods: We investigated the links between observed parent-child relationship quality in an interaction task and antibody response to meningococcal conjugate vaccine in a longitudinal study of 164 ambulatory 10-11 year-old children; additional analyses examine associations with cortisol reactivity, BMI, and somatic illness., Results: Observed Negative/Conflict behavior in the interaction task predicted a less robust antibody response to meningococcal serotype C vaccine in the child over a 6 month-period, after controlling for socio-economic and other covariates. Observer rated interaction conflict also predicted increased cortisol reactivity following the interaction task and higher BMI, but these factors did not account for the link between relationship quality and antibody response., Conclusions: The results begin to document the degree to which a major source of child stress exposure, parent-child relationship conflict, is associated with altered immune system development in children, and may constitute an important public health consideration., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Current measures of implementer fidelity often fail to adequately measure core constructs of adherence and competence, and their relationship to outcomes can be mixed. To address these limitations, we used observational methods to assess these constructs and their relationships to proximal outcomes in a randomized trial of a school-based preventive intervention (Rochester Resilience Project) designed to strengthen emotion self-regulation skills in first-third graders with elevated aggressive-disruptive behaviors. Within the intervention group (n = 203), a subsample (n = 76) of students was selected to reflect the overall sample. Implementers were 10 paraprofessionals. Videotaped observations of three lessons from year 1 of the intervention (14 lessons) were coded for each implementer-child dyad on adherence (content) and competence (quality). Using multilevel modeling, we examined how much of the variance in the fidelity measures was attributed to implementer and to the child within implementer. Both measures had large and significant variance accounted for by implementer (competence, 68 %; adherence, 41 %); child within implementer did not account for significant variance indicating that ratings reflected stable qualities of the implementer rather than the child. Raw adherence and competence scores shared 46 % of variance (r = .68). Controlling for baseline differences and age, the amount (adherence) and quality (competence) of program delivered predicted children's enhanced response to the intervention on both child and parent reports after 6 months, but not on teacher report of externalizing behavior. Our findings support the use of multiple observations for measuring fidelity and that adherence and competence are important components of fidelity which could be assessed by many programs using these methods.

Research findings in psychoneuroimmunology document reliable, bidirectional linkages among psychological processes, the nervous system, and the immune system. However, available data are based almost entirely on animal and adult human studies; the application to children and adolescents is uncertain. We capitalized on the experimental leverage provided by a routine vaccination to examine the link between mood symptoms and the immune response to a vaccine challenge in early adolescence. One hundred twenty-six 11-year-olds for whom vaccine response data were available were assessed at prevaccination and 4 weeks, 3 months, and 6 months following vaccination; self-report ratings of depression and anxiety as well as measures of psychosocial and somatic risk were assessed prior to vaccine response. Analyses indicated that children's internalizing mood symptoms were associated with elevated and persistently higher antibody responses, with evidence extending to two of the four serogroups. The associations remained after controlling for multiple possible confounders (social class, body mass index, sleep, psychosocial risk, and pubertal status). The observed enhanced vaccine response associated with depressive and anxious symptoms in early adolescence may reflect an important developmental difference in immune system-brain interplay between adults and children, and it underscores the need for further developmental studies of psychoneuroimmunology.

The 2012 National Strategy for Suicide Prevention expands the current suicide prevention paradigm by including a strategic direction aimed at promoting healthy populations. Childhood and adolescence are key suicide prevention window periods, yet knowledge of suicide prevention pathways through universal interventions is limited (Aspirational Goal 11). Epidemiologic evidence suggests that prevention programs in normative social systems such as schools are needed for broad suicide prevention impact. Prevention trial results show that current universal prevention programs for children and young adolescents are effective in reducing adolescent emotional and behavioral problems that are risk factors for suicidal behavior, and in the case of the Good Behavior Game, suicide attempts. A developmentally sequenced upstream suicide prevention approach is proposed: (1) childhood programs to strengthen a broad set of self-regulation skills through family and school-based programs, followed by (2) adolescent programs that leverage social influences to prevent emerging risk behaviors such as substance abuse and strengthen relationships and skills. Key knowledge breakthroughs needed are evidence linking specific intervention strategies to reduced suicidal behaviors and mortality and their mechanisms of action. Short- and long-term objectives to achieve these breakthroughs include combining evidence from completed prevention trials, increasing motivators for prevention researchers to assess suicide-related outcome, and conducting new trials of upstream interventions in populations using efficient designs acceptable to communities. In conclusion, effective upstream prevention programs have been identified that modify risk and protective factors for adolescent suicide, and key knowledge breakthroughs can jump-start progress in realizing the suicide prevention potential of specific strategies., (Copyright © 2014 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Adolescent suicide is a major public health concern. Stressing the need for public health-based solutions, the Centers for Disease Control and Prevention identified "connectedness" as one means of pursuing this agenda. To advance this effort in suicide prevention with adolescents, (1) consistencies and variation in the literature overtly linking connectedness to suicide thoughts and behaviors (STB) are reviewed, (2) three more specific mechanistic pathways are proposed whereby connectedness may influence STB, and (3) several implications related to use of connectedness as a public health framework for adolescent suicide prevention and intervention are outlined., (© 2014 The American Association of Suicidology.)

To develop and refine interventions to prevent youth suicide, knowledge is needed about specific processes that reduce risk at a population level. Using a cross-sectional design, the present study tested hypotheses regarding associations between self-reported suicide attempts, emotion regulation difficulties, and positive youth-adult relationships among 7,978 high-school students (48.6% male, 49.9% female) in 30 high schools from predominantly rural, low-income communities. 683 students (8.6%) reported a past-year suicide attempt. Emotion regulation difficulties and a lack of trusted adults at home and school were associated with increased risk for making a past-year suicide attempt, above and beyond the effects of depressive symptoms and demographic factors. The association between emotion regulation difficulties and suicide attempts was modestly lower among students who perceived themselves as having higher levels of trusted adults in the family, consistent with a protective effect. Having a trusted adult in the community (outside of school and family) was associated with fewer suicide attempts in models that controlled only for demographic covariates, but not when taking symptoms of depression into account. These findings point to adolescent emotion regulation and relationships with trusted adults as complementary targets for suicide prevention that merit further intervention studies. Reaching these targets in a broad population of adolescents will require new delivery systems and "option rich" (OR) intervention designs.

Suicide is a leading cause of death among adolescents, many of whom fail to disclose suicide concerns to adults who might help. This study examined patterns and predictors of help-seeking behavior among adolescents who seriously considered suicide in the past year. 2,737 students (50.9 % female, 46.9 % male; racial distribution 79.5 % Caucasian, 11.9 % Hispanic/Latino, and 3.6 % Black/African-American) from 12 high schools in rural/underserviced communities were surveyed to assess serious suicide ideation (SI) in the past year, disclosure of SI to adults and peers, attempts to get help, attitudes about help-seeking, perceptions of school engagement, and coping support. Help-seeking was defined as both disclosing SI to an adult and perceiving oneself as seeking help. The relationship between adolescents' help-seeking disclosure and (1) help-seeking attitudes and (2) perceptions of social resources was examined among suicidal help-seeking youth, suicidal non-help-seeking youth, and non-suicidal youth. Of the 381 (14 %) students reporting SI, only 23 % told an adult, 29 % sought adult help, and 15 % did both. Suicidal help-seekers were similar to non-suicidal peers on all measures of help-seeking attitudes and social environment perceptions. Positive attitudes about help-seeking from adults at school, perceptions that adults would respond to suicide concerns, willingness to overcome peer secrecy requests, and greater coping support and engagement with the school were associated with students' increased disclosure of SI and help-seeking. This study supports prevention strategies that change student norms, attitudes and social environments to promote help-seeking among adolescents with SI. Promising intervention targets include increasing students' perceptions of the availability and capability of adults to help them, and strengthening students' understanding of how existing resources can help them cope.

We examined associations between Latino adolescents' school engagement and their likelihood of disclosing suicidal ideation (SI) to adults and of asking for help for SI. A first set of analyses was conducted on a total sample of 14 high schools, and a second set of analyses was conducted on 8 "Latino-representative" high schools. The criterion for Latino representation was that ≥10% of the school's total student population was Latino. Across all 14 high schools, 17% (110/663) of Latino students reported SI in the past year, compared to 13% (359/2,740) of non-Hispanic White students and 11% (78/719) of African American students. Of Latino students with SI, 24% (26/110) told an adult and 35% (38/110) sought help. In the 8 Latino-representative schools, higher levels of reported school engagement were associated with a greater likelihood of seeking help (OR = 6.17) and disclosure of SI to an adult (OR = 7.64) for Latino males. For Latinas, however, school engagement was not associated with either disclosure of SI to an adult or seeking help. Additional research is needed to clarify the processes, including social connectedness, that contribute to the disclosure of and help-seeking for SI among Latino adolescents.

Validated measures that can be administered to school populations are needed to advance knowledge of help-seeking processes and to evaluate suicide prevention programs that target help-seeking. With 6,370 students from 22 high schools, we assessed the psychometric properties of three brief measures: Help-Seeking Acceptability at School, Adult Help for Suicidal Youth, and Reject Codes of Silence. Internal consistency coefficients ranged from .64 to .84. In support of construct validity, lower scores on each scale were associated with more maladaptive coping norms; for each one unit increase on each scale, students were one third to one half as likely to report suicidal ideation, suicide attempts, and elevated depression., (© 2012 The American Association of Suicidology.)

Experimental animal studies and adult research consistently show that stress exposure and/or psychological symptoms are associated with poorer health and immune functioning. The application to children is not yet clear, however, and we lack developmental models for studies in this area. The objective of this paper was to test the hypothesis that self-reported self-efficacy and depression, two markers of psychological well-being in children, would predict immunity and rate of illnesses. The data are based on a prospective study of 141 healthy, normally developing children aged 7-13 years who were recruited from an ambulatory pediatric setting. Children completed self-efficacy and depression measures and had blood obtained for IL-6 plasma levels and natural killer cell functional assays on three occasions, 6 months apart. Parents maintained weekly child illness diaries over 1 year using a thermometer to record fever. Parent psychiatric symptoms and income were used as covariates. Results indicated that, across the three occasions of measurement collected over the 1-year period, higher perceived self-efficacy was significantly associated with lower plasma interleukin 6 concentrations. There was no overall main effect of depressive symptoms on immune measures; however, for older girls, higher depression was associated with elevated natural killer cell cytotoxicity and an increased rate of total illnesses and febrile illnesses. The findings provide some of the first evidence that psychological processes are associated with immunity and health in a normally developing sample of preadolescents. Furthermore, the pattern of results suggests a modified model of a link between psychological well-being and immunological processes in children. These results build on and expand research on the notion of allostatic load and develop a groundwork for developmental studies in this area.

A series of N-substituted 3-(4-piperidinyl)-1,3-benzoxazolinones and oxindoles are reported which were found to be potent and selective muscarinic M1 agonists. By control of the physicochemical characteristics of the series, particularly the lipophilicity, compounds with good metabolic stability and excellent brain penetration were identified. An exemplar of the series was shown to be pro-cognitive in the novel object recognition rat model of temporal induced memory deficit., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

A model for teaching children skills to strengthen emotional self-regulation is introduced, informed by the developmental concept of scaffolding. Adult modeling/instruction, role-play and in vivo coaching are tailored to children's level of understanding and skill to promote use of skills in real life contexts. Two-hundred twenty-six kindergarten-3rd grade children identified with elevated behavioral and social classroom problems from a population-based screening participated in a wait listed randomized trial of the Rochester Resilience Project derived from this model. In 14 lessons with school-based mentors, children were taught a hierarchical set of skills: monitoring of emotions; self control/ reducing escalation of emotions; and maintaining control and regaining equilibrium. Mentors provided classroom reinforcement of skill use. Multi-level modeling accounting for the nesting of children in schools and classrooms showed the following effects at post-intervention: reduced problems rated by teachers in behavior control, peer social skills, shy-withdrawn and off-task behaviors (ES 0.31-0.47). Peer social skills improved for girls but not for boys. Children receiving the intervention had a 46% mean decrease in disciplinary referrals and a 43% decrease in suspensions during the 4-month intervention period. Limitations and future directions to promote skill transfer are discussed.

8.6% suicidal ideation (SI) was found among 349 urban 6-9 year olds in the top tercile of aggressive-disruptive behavior. SI was associated with more self-reported depression, ODD, conduct problems, and ADHD symptoms (ES 0.70-0.97) and 3.5-5 times more clinically significant symptoms. Parents rated more symptoms in older children associated with SI compared to parents of similar age children without SI, including greater somatic and behavior problems in 8-9 year olds with SI. Parent ratings did not differentiate SI and non-SI in 6-7 year olds. SI frequently co-occurred with thoughts about death. Children described anger, dysphoria and interpersonal conflict as motivators/triggers for SI and worries about safety/health as motivator/triggers for thoughts about death, suggesting that problems managing emotionally challenging situations are a specific factor in initiating SI. Universal and indicated interventions for children to strengthen emotional self-regulation and behavioral control are recommended to complement the current emphasis on suicide prevention among adolescents.

Lead optimisation starting from the previously reported selective quinoline NK(3) receptor antagonists talnetant 2 (SB-223412) and 3 (SB-222200) led to the identification of 3-aminoquinoline NK(3) antagonist 10 (GSK172981) with excellent CNS penetration. Investigation of a structurally related series of sulfonamides with reduced lipophilicity led to the discovery of 20 (GSK256471). Both 10 and 20 are high affinity, potent NK(3) receptor antagonists which despite having different degrees of CNS penetration produced excellent NK(3) receptor occupancy in an ex vivo binding study in gerbil cortex.

A series of 5-(piperidinylethyloxy)quinoline 5-HT(1) receptor ligands have been studied by elaboration of the series of dual 5-HT(1)-SSRIs reported previously. These new compounds display a different in vitro pharmacological profile with potent affinity across the 5-HT(1A), 5-HT(1B) and 5-HT(1D) receptors and selectivity against the serotonin transporter. Furthermore, they have improved pharmacokinetic profiles and CNS penetration.

This study investigated the relation between suicide attempts and immigrant generation status using the Latino subset of the National Longitudinal Study of Adolescent Health, a school-based, nationally representative sample. This study also examined whether generation status predicted risk factors associated with elevated suicide behaviors, namely illicit substance use, problematic alcohol use, and depressive symptoms. Finally, hypothesizing that elevated depressive symptoms and substance use mediate the relation between immigrant generation status and suicide attempts among Latino adolescents, a path model was tested. Our findings revealed immigrant generation status was a determinant for suicide attempts, problematic alcohol use, repeated marijuana use, and repeated other drug use for Latino adolescents. US-born Latinos with immigrant parents (i.e., second-generation youth) were 2.87 (95% CI, 1.34, 6.14) times more likely to attempt suicide, 2.27 (95% CI, 1.53, 3.35) times more likely to engage in problematic alcohol use, 2.56 (95% CI, 1.62, 4.05) times more likely to engage in repeated marijuana use, and 2.28 (95% CI, 1.25, 4.17) times more likely to engage in repeated other drug use than were foreign-born youth (i.e., first-generation youth). Later-generations of US-born Latino youth with US-born parents were 3.57 (95% CI, 1.53-8.34) times more likely to attempt suicide, 3.34 (95% CI, 2.18-5.11) times more likely to engage in problematic alcohol use, 3.90 (95% CI, 2.46, 6.20) times more likely to engage in repeated marijuana use, and 2.80 (95% CI, 1.46, 5.34) times more likely to engage in repeated other drug use than were first-generation youth. Results from the path analysis indicated that repeated other drug use may mediate the effect of generation status on suicide attempts.

Objective: Family processes have a substantial impact on children's social and emotional well-being, but little is known about the effects of family stress on children's physical health. To begin to identify potential links between family stress and health in children, we examined associations between specific aspects of family psychosocial stress and the frequency of illnesses in children, measures of innate and adaptive immune function, and human herpesvirus 6 (HHV-6) reactivation., Study Design: Prospective study of 169 ambulatory school-age children and parents. Parents completed multiple assessments of stress at 7 sequential six-month visits and maintained weekly illness diaries for their children over three years using a thermometer to record fever. Children had blood obtained for HHV-6 and immune function studies at each visit including natural killer (NK) cell function and the percentage of CD4 and CD8 cells associated with immune control of cytomegalovirus (CMV)., Results: Parental psychiatric symptoms were associated with a higher frequency of illnesses: for each 1 U increase in symptom score children had an increased 1-year rate of total illnesses of 40% (rate ratio, 1.40; 95% CI, 1.06-1.85) and febrile illnesses of 77% (rate ratio, 1.77, 95% CI, 1.00-3.13). Parental psychiatric symptom scores were also associated with enhanced NK cell function (estimate, 0.15; 95% CI, 0.05-0.26) and increased percentages of CD8+CD28-CD57+ cells in the blood of CMV seropositive children (estimate, 2.57; 95% CI, 0.36-4.79). HHV-6 reactivation was not detected., Conclusions: There is an association between specific psychosocial stress exposure and rates of illness and immune function in normally developing children.

Randomized field trials provide unique opportunities to examine the effectiveness of an intervention in real world settings and to test and extend both theory of etiology and theory of intervention. These trials are designed not only to test for overall intervention impact but also to examine how impact varies as a function of individual level characteristics, context, and across time. Examination of such variation in impact requires analytical methods that take into account the trial's multiple nested structure and the evolving changes in outcomes over time. The models that we describe here merge multilevel modeling with growth modeling, allowing for variation in impact to be represented through discrete mixtures--growth mixture models--and nonparametric smooth functions--generalized additive mixed models. These methods are part of an emerging class of multilevel growth mixture models, and we illustrate these with models that examine overall impact and variation in impact. In this paper, we define intent-to-treat analyses in group-randomized multilevel field trials and discuss appropriate ways to identify, examine, and test for variation in impact without inflating the Type I error rate. We describe how to make causal inferences more robust to misspecification of covariates in such analyses and how to summarize and present these interactive intervention effects clearly. Practical strategies for reducing model complexity, checking model fit, and handling missing data are discussed using six randomized field trials to show how these methods may be used across trials randomized at different levels.

Gatekeeper-training programs, designed to increase identification and referral of suicidal individuals, are widespread but largely untested. A group-based randomized trial with 32 schools examined impact of Question, Persuade, Refer (QPR) training on a stratified random sample of 249 staff with 1-year average follow-up. To test QPR impact, the authors introduced and contrasted 2 models of gatekeeper-training effects in a population: gatekeeper surveillance and gatekeeper communication. Intent-to-treat analyses showed that training increased self-reported knowledge (effect size [ES] = 0.41), appraisals of efficacy (ES = 1.22), and service access (ES = 1.07). Training effects varied dramatically. Appraisals increased most for staff with lowest baseline appraisals, and suicide identification behaviors increased most for staff already communicating with students about suicide and distress. Consistent with the communication model, increased knowledge and appraisals were not sufficient to increase suicide identification behaviors. Also consistent with the communication model were results from 2,059 8th and 10th graders surveyed showing that fewer students with prior suicide attempts endorsed talking to adults about distress. Skill training for staff serving as "natural gatekeepers" plus interventions that modify students' help-seeking behaviors are recommended to supplement universal gatekeeper training.

Epidemiological considerations point to a small handful of prevention strategies that have the potential for dramatically reducing suicide rates. Nearly all of those prevention approaches involve population-based strategies to either find an increased number of individuals at high risk for suicide or to reduce the prevalence of risk factors in members of a population that, as a whole, has a relatively low rate of suicide. Few of these approaches have been evaluated in rigorous trials. We argue that there are rigorous randomized trial designs that are both feasible and ethical and can be used to test both programmes and implementation strategies for population-based suicide prevention. We review existing suicide prevention trials and introduce two new randomized trial designs that are likely to achieve sufficient statistical power. The 'dynamic wait-listed design' randomizes across different time periods and is now being used to test a gatekeeper training programme in 32 schools. It could also be used to examine suicide prevention programmes in rural areas. The multi-trial follow-up study builds on the large number of successful population-based preventive interventions aimed at reducing known risk factors for suicide in youths to see whether these also cause a reduction in rates of completed suicide.

Objective: To examine prospective associations between chronic stress in the parent-child and family systems and subsequent rates of illnesses and the activity of natural killer (NK) cells in children., Design: Prospective cohort study., Setting: The Golisano Children's Hospital at Strong, Rochester, NY, from July 1, 2001, to June 30, 2003., Participants: One hundred sixty-nine socioeconomically and racially diverse children (aged 5-10 years) and their parents. Parents completed measures of their psychiatric symptoms and stress in the family every 6 months. Children's blood samples were obtained for NK cytotoxicity assays every 6 months., Main Outcome Measures: Parent-reported total child illnesses and febrile illnesses and results of NK cell cytotoxicity assays. We estimated adjusted illness rate ratios and adjusted mean differences in NK activity., Results: Elevated parental psychiatric symptoms occurring with family stressors were associated with more total illnesses (rate ratio, 1.11; 95% confidence interval [CI], 1.00-1.22) and febrile illnesses (rate ratio, 1.36; 95% CI, 1.13-1.64) in children. Natural killer cell function was enhanced in children whose parents reported more chronic stress (estimate, 0.15; 95% CI, 0.05-0.26). Natural killer cell function was not associated with short-term changes in stress. Stress-illness relationships were not associated with stress-related alterations in NK cell function., Conclusions: Chronic family stress was associated with increased illnesses in children. Unlike older adults, children living with elevated chronic stress had enhanced rather than decreased NK cytotoxicity, suggesting chronic stress may have different effects on the developing immune system. Impaired parental functioning may be a mechanism linking family stress with adverse effects on children's health.

Despite increasing dissemination of prevention programs, little is known about program implementers, including factors that promote satisfying job roles. Using Self-Determination Theory as a conceptual framework, we surveyed 128 implementers of the widely disseminated Primary Mental Health Project. Implementers reported 7.1 years average experience on the job (range 1-25 years), and 55% had two or more years of college. In a multivariate regression model, predictors of higher job satisfaction were: lower education level; positive perceptions of supervision and continuing education opportunities; and satisfaction at work of needs for autonomy and competence. For implementers with 3 years experience, satisfaction of needs for autonomy and for relatedness predicted job satisfaction. Contrary to expectations, job satisfaction was unrelated to anticipated job retention.

Background: The traditional wait-listed design, where half are randomly assigned to receive the intervention early and half are randomly assigned to receive it later, is often acceptable to communities who would not be comfortable with a no-treatment group. As such this traditional wait-listed design provides an excellent opportunity to evaluate short-term impact of an intervention. We introduce a new class of wait-listed designs for conducting randomized experiments where all subjects receive the intervention, and the timing of the intervention is randomly assigned. We use the term "dynamic wait-listed designs" to describe this new class., Purpose: This paper examines a new class of statistical designs where random assignment to intervention condition occurs at multiple times in a trial. As an extension of a traditional wait-listed design, this dynamic design allows all subjects to receive the intervention at a random time. Motivated by our search for increased statistical power in an ongoing school-based trial that is testing a program of gatekeeper training to identify suicidal youth and refer them to treatment, this new design class is especially useful when the primary outcome is a count or rate of occurrence, such as suicidal behavior, whose rate can fluctuate over time due to uncontrolled factors., Methods: Statistical power is computed for various dynamic wait-listed designs under conditions where the underlying rate of occurrence is allowed to vary nonsystematically. We also present as an example a large ongoing trial to evaluate a gatekeeper training suicide prevention program in 32 schools which we initially began as a classic randomized wait-listed design. The primary outcome of interest in this study is the count of the number of children who are identified by the school system as having suicidal thoughts or behaviors who are then validated as being suicidal by mental health professionals in the community., Results: A general result shows that dynamic wait-listed designs always have higher statistical power over a traditional wait-listed design. This power increase can be substantial. Efficiency gains of 33% are easy to obtain for situations where the intervention has a small effect and the variation in rate across time is quite high. When the rate variation for an outcome is very low or the intervention effect is large, efficiency gains approach 100%. A small increase in the number of times where random assignment occurs from 2 - for the standard wait-listed design, to say 4 can provide a large reduction in variance. Efficiency gains can also be high when converting standard wait-listed design to a dynamic one half-way into the study., Limitations: As with all wait-listed designs, dynamic wait-listed designs can only be used to evaluate short-term impact. Since all subjects eventually receive the intervention, no comparison can be made after the end of the random assignment period. The statistical power benefits are primarily limited to outcomes that can be treated as count or time to event data., Conclusions: A dynamic design randomly assigns units - either individuals or groups - to start the intervention at varying times during the course of the study. This design is useful in testing interventions that screen for new or existing cases, as well as testing the scalability of interventions as they are disseminated or expanded system wide. They can improve on the traditional wait-listed design both in terms of statistical power and robustness in the presence of exogenous factors. This paper demonstrates that such designs yield smaller standard errors and can achieve higher statistical power than that of a standard wait-listed design. Just as important, dynamic designs can also help reduce the logistical challenges of implementing an intervention on a wide scale. When the intervention requires that significant training resources be allocated throughout the study, the dynamic wait-listed design is likely to increase the rate of training and lead to a higher level of program implementation.

An SAR study around the mixed 5-HT1ABD receptor antagonist SB-272183 found that introduction of cis-2,6-dimethyl substitution onto the piperazine ring was a key structural change, which imparted a combination of both excellent selectivity over the 5-HT1A and 5-HT1D receptors and low intrinsic activity. This led to the identification of the selective 5-HT1B receptor antagonist SB-616234.

Vanilloid receptor-1 (TRPV1) is a non-selective cation channel, predominantly expressed by peripheral sensory neurones, which is known to play a key role in the detection of noxious painful stimuli, such as capsaicin, acid and heat. To date, a number of antagonists have been used to study the physiological role of TRPV1; however, antagonists such as capsazepine are somewhat compromised by non-selective actions at other receptors and apparent modality-specific properties. SB-366791 is a novel, potent, and selective, cinnamide TRPV1 antagonist isolated via high-throughput screening of a large chemical library. In a FLIPR-based Ca(2+)-assay, SB-366791 produced a concentration-dependent inhibition of the response to capsaicin with an apparent pK(b) of 7.74 +/- 0.08. Schild analysis indicated a competitive mechanism of action with a pA2 of 7.71. In electrophysiological experiments, SB-366791 was demonstrated to be an effective antagonist of hTRPV1 when activated by different modalities, such as capsaicin, acid or noxious heat (50 degrees C). Unlike capsazepine, SB-366791 was also an effective antagonist vs. the acid-mediated activation of rTRPV1. With the aim of defining a useful tool compound, we also profiled SB-366791 in a wide range of selectivity assays. SB-366791 had a good selectivity profile exhibiting little or no effect in a panel of 47 binding assays (containing a wide range of G-protein-coupled receptors and ion channels) and a number of electrophysiological assays including hippocampal synaptic transmission and action potential firing of locus coeruleus or dorsal raphe neurones. Furthermore, unlike capsazepine, SB-366791 had no effect on either the hyperpolarisation-activated current (I(h)) or Voltage-gated Ca(2+)-channels (VGCC) in cultured rodent sensory neurones. In summary, SB-366791 is a new TRPV1 antagonist with high potency and an improved selectivity profile with respect to other commonly used TRPV1 antagonists. SB-366791 may therefore prove to be a useful tool to further study the biology of TRPV1.